Chapter 6. Types and Pain Flashcards

Question 1

Q

A45-year-old patient with metastatic breast carcinoma
is prescribed 30 mg of sustained-release
morphine (MS Contin) twice a day and one
15-mg tablet of immediate-release morphine
(MSIR) every 6 hours as needed for breakthrough
pain. On her routine follow-up visit she
reports that she routinely uses MSIR four times
a day with satisfactory pain control on most days
and no major side effects. What would be your
best course of action in this situation?
(A) Prescriptions should be left unchanged
(B) MS Contin should be changed to 40 mg
of OxyContin twice a day and 5 mg of
oxycodone every 6 hours as needed for
breakthrough pain
(C) Fentanyl patch of 25 μg/h should
replace MS Contin with 15 mg of MSIR
every 6 hours as needed for breakthrough
pain
(D) MS Contin should be increased to 60 mg
twice a day with MSIR 15 mg every
6 hours as needed for breakthrough pain
(E) MS Contin should be increased to
60 mg twice a day, and MSIR should be
discontinued

Answer

A

(D) If a patient routinely uses breakthrough
medications, the daily total amount should be
converted to a sustained-release dose and
added to the current maintenance dose.

Question 2

Q

333. Approximately in what percentage of patients
with malignancies does pain unrelated to cancer
occur?
(A) Less than 2%
(B) 3%
(C) 7.5%
(D) 11%
(E) 25%

Answer

A

(B) Approximately 3% of pain syndromes in
cancer patients are unrelated to the underlying
malignancy or cancer treatment. Most commonly,
pain is caused by degenerative disc disease,
arthritis, fibromyalgia, or migraine and
has often predated the diagnosis of cancer.

Question 3

Q

There is a significant incidence of neuropathic
pain in a cancer patient with brachial plexopathy.
The etiology of the brachial plexopathy in such
a patient may be caused by direct tumor infiltration
or radiation fibrosis. Electrophysiologic
evaluation with nerve conduction velocity (NCV)
study and electromyography (EMG) helps to
distinguish between the two etiologies. Which of
the following findings of NCV/EMG is the most
helpful to differentiate between the direct tumor
infiltration and the radiation fibrosis etiologies of
brachial plexopathy?
(A) Segmental nerve conduction slowing
(B) Myokymia
(C) Fibrillation potentials
(D) Positive sharp waves
(E) Decreased amplitude of the compound
muscle action potential (CMAP)

Answer

A

(B) Segmental nerve conduction slowing, fibrillation
potentials, positive sharp waves, and
decreased amplitude CMAPs are all helpful in
determining the presence of brachial plexopathy
in general. Myokymia is present in 63% of
patients with radiation fibrosis induced
brachial plexopathy. Brachial plexopathy
caused by direct tumor infiltration has a low
incidence of myokymia. Myokymia is a continuous
but brief involuntary muscle twitching
that gives the appearance of wormlike rippling
of the muscle. It

Question 4

Q

335. If bony metastases are present, which primary
cancer location has the best 5-year survival
prognosis?
(A) Myeloma
(B) Breast
(C) Prostate
(D) Thyroid
(E) Kidney

Answer

A

(D) A5-year survival for a cancer patient with
documented skeletal metastases varies widely
depending on location of the primary tumor:
myeloma—10%; breast—20%; prostate—25%;
lung—less than 5%; kidney—10%; thyroid—
40%; melanoma—less than 5%.

Question 5

Q

The most frequent spinal cord symptom or sign
in patients with carcinomatous meningitis is
(A) nuchal rigidity
(B) back pain
(C) reflex asymmetry
(D) positive straight leg raise test
(E) weakness

Answer

A

(C) Reflex asymmetry occurs in 67% of patients
with carcinomatous meningitis and is the most
frequent spinal cord–related sign. The frequency
of nuchal rigidity, back pain, positive straight leg raise test, and weakness is 11%,
25%, 13%, and 33%, respectively.

Question 6

Q

Which of the following would most likely be
responsible for the central pain syndrome?
(A) Epidural spinal cord compression
(B) Metastatic bony destruction of the
vertebrae with a nerve root compression
(C) Metastatic involvement of the cranial
nerves
(D) Carcinomatous meningitis
(E) Radiation myelopathy

Answer

A

(E) Central pain syndromes are relatively rare in
cancer patients. Although epidural spinal cord
compression is almost always painful, central pain
is not the predominant symptom. Nociceptive
input from progressive bony destruction by
metastases is the usual cause of pain, with or without
concurrent radicular pain from nerve root
compression. Radiation myelopathy is the central
pain syndrome.

Question 7

Q

338. The majority of patients with epidural metastasis
have the following pattern of pain:
(A) Local
(B) Radicular
(C) Referred
(D) Funicular
(E) All of the above

Answer

A

(A) The most common pattern of pain in patients
with epidural metastasis is local. Local pain over
the involved vertebral body, which results from
the involvement of the vertebral periosteum, is
dull and exacerbated by recumbency.
Radicular pain from compressed or damaged
nerve roots is usually unilateral in the
cervical and lumbosacral regions and bilateral
in the thorax. The pain is experienced in the
overlying spine, deep in certain muscles supplied
by the compressed root, and in the cutaneous
distribution of the injured root.
Referred pain has a deep aching quality
and is often associated with tenderness of
subcutaneous tissues and muscles at the site
of referral. The typical examples of referred
pain pattern include buttocks and posterior
thigh pain with lumbosacral spine involvement;
pain in the flank, groin, and anterior
thigh in the upper lumbar spine involvement;
midscapular and shoulder pain in the cervicothoracic
epidural disease.
Funicular pain usually occurs some distance
below the site of compression and it has hot or cold qualities in a poorly localized nondermatomal
distribution. It presumably results
from compression of the ascending sensory
tracts in the spinal cord.

Question 8

Q

All of the following are true about the World
Health Organization (WHO) analgesic ladder,
EXCEPT
(A) it is a method for relief of cancer pain
based on a small number of relatively
inexpensive drugs
(B) it has three steps
(C) step one involves the use of opioids
(D) it suggests to use only one drug from
each group at a time
(E) it is a simple and effective method for
controlling cancer pain

Answer

A

(C) The WHO analgesic ladder is based on the
premise that most patients throughout the world
gain adequate pain relief if health care professionals
learn how to use a few effective and
relatively inexpensive drugs well. Step 1 of the
ladder involves the use of nonopioids. If this
step is ineffective, go to step 2 and add an
opioid for mild to moderate pain. Step 3 substitutes
an opioid for moderate to severe pain
in step 2. Only one drug from each group
should be used at a time. Adjuvant drugs can
be used in all steps.

Question 9

Q

340. The following are all true about methadone,
EXCEPT
(A) it has a highly variable oral bioavailability
(B) it is a low cost medication
(C) it has no known active metabolites
(D) it has N-methyl-D-aspartate (NMDA)
receptor agonist properties
(E) it has high lipid solubility

Answer

A

(D) Methadone has a variable oral bioavailability
between 41% and 99% and, therefore,
should be started with extra caution (low initial
dose and slow subsequent increases).
Methadone differs from all other opioids by its
noncompetitive antagonist activity at the
NMDAreceptors. Activation of NMDA receptors
has been shown to play a role in development
of tolerance to analgesic effects of
opioids, as well as in the pathologic sensory
states, such as neuropathic pain, inflammatory
pain, ischemic pain, allodynia, and spinal
states of hypersensitivity.

Question 10

Q

58-years-old patient with metastatic prostate
cancer is taking sustained-release morphine
(MS Contin) every 8 hours with a total daily
dose of 225 mg with optimal pain control.
Because of some circumstances, he has to be
converted to transdermal therapeutic system
fentanyl (TTS-fentanyl). What is the correct
dose of fentanyl patch equivalent to the current
dose of MS Contin for this patient?
(A) 25 μg/h every 72 hours
(B) 50 μg/h every 48 hours
(C) 75 μg/h every 72 hours
(D) 100 μg/h every 48 hours
(E) 125 μg/h every 72 hours

Answer

A

(C) As a rough guide for conversion, the 8-hourly
dose of MS Contin (225/3 = 75 mg in this case)
can be considered equal to the micrograms per
hour dose of TTS-fentanyl. In one study, most
people had satisfactory pain profiles with frequency
of administration of every 3 days. Only
in 24% of subjects in the study required different
frequency of administration varying from
48 to 60 hours.

Question 11

Q

Which of the following is true with respect to
central pain syndromes?
(A) The most common cause of central pain
state are lesions located in the brainstem
(B) The Wallenberg syndrome (lateral
medullar syndrome) is characterized by
contralateral facial sensory loss and
Horner syndrome
(C) The most common lesions that produce
thalamic pain syndrome are infarctions
(D) Spinal cord lesions rarely cause sensory
deficits
(E) Central pain syndromes of spinal origin
usually respond to epidural steroids

Answer

A

(C)
A. The most common cause of central pain
states are spinal cord lesions.
B. The Wallenberg syndrome is usually vascular
in origin, and characterized by crossed
sensory findings that include ipsilateral
facial sensory loss, Horner syndrome, and contralateral body impairment of pain and
temperature loss.
C. The most common lesions that produce thalamic
pain syndrome are infarctions, followed
by arteriovenous malformations (AVMs),
neoplasms, abscesses, plaque of multiple
sclerosis, traumatic injury, and others.
D. Spinal cord lesions are the most common
cause of central pain syndromes and present
with areas of sensory loss resulting
from disruption of the spinothalamic tract.
E. The treatment of central pain of spinal origin
is complex with poor response to most
forms of therapy.

Question 12

Q

343. Peripheral neuropathy is a common pain syndrome
characterized by which of the following?
(A) Asymmetric paresthesias and proximal
motor impairment
(B) Proximal more than distal sensory
impairment
(C) Most peripheral neuropathies may be
classified as demyelinating, axonal, or
mixed
(D) Peripheral mononeuropathy is the most
common peripheral nerve disease in
patients with long-standing diabetes
mellitus
(E) Nerve conduction studies only measure
conduction through small unmyelinated
fibers, so impairment of the fast
conducting fibers may go undetected

Answer

A

(C) Sensory symmetric impairment is commonly
seen distally with progression to more
proximal areas of the limbs as the disease progresses.
Peripheral polyneopathy is the most
common initial manifestation of diabetes mellitus.
The nerve conduction studies measure
only the fastest conducting fibers, leaving
injury of small-diameter fibers, which transmit
pain sensations, undiagnosed.

Question 13

Q

Events seen in the development of neuropathic
pain are
(A) following nerve injury, there is a
decreased activity of the sodium channels
which allows for abnormal conduction
through pain facilitating fibers
(B) wide dynamic range neurons in the
dorsal horn respond with increased
frequency as the intensity of the
repeated afferent stimulus increases
(C) an increase in potassium channels would
facilitate an amplified afferent activity
(D) C-polymodal nociceptors are activated
by low-threshold mechanical, thermal,
and chemical stimuli
(E) γ-aminobutyric acid (GABA) and
glycine are released in the dorsal horn
and augment the response of second
order neurons

Answer

A

(B) Following nerve injury there is an increase
in the expression of sodium channels in the
neuroma and in the DRG. Consistent with the
role of sodium channels in the development of
neuropathic pain is blockage of their activity by
low plasma concentrations of lidocaine. A reduction
in potassium channel activity leads to
increased afferent activity. The largest population
of afferent axons is C-polymodal nociceptors
that are activated by high-threshold
mechanical, thermal, and chemical stimuli.

Question 14

Q

Examples of neuropathic pain conditions include
all, EXCEPT
(A) complex regional pain syndrome (CRPS)
(B) diabetic peripheral neuropathy
(C) postherpetic neuralgia (PHN)
(D) Raynaud phenomenon
(E) phantom limb pain

Answer

A

(D) Raynaud phenomenon is not a neuropathic
pain condition, but rather a vascular condition
(although, potentially sympathetically mediated
and/or sustained).

Question 15

Q

Which of the following conditions is more
likely to be associated with neuropathic pain?
(A) Traumatic nerve injury
(B) Stroke
(C) Syringomyelia
(D) Multiple sclerosis
(E) Large myelinated fiber neuropathy

Answer

A

(C) Although not completely known some conditions
predispose to the development of neuropathic
pain. The relative frequency is 5% for
patients with traumatic nerve injury, 8% for
patients after stroke, 28% for patients with multiple
sclerosis, and 75% for patients with
syringomyelia. Neuropathies with predominant involvement of large myelinated fibers are usually
not painful.

Question 16

Q

A patient with CRPS responds well to sympathetic
ganglion block. The results of this block
can lead you to say which of the following
about this particular pain condition?
(A) It is vascularly mediated
(B) It is sympathetically mediated
(C) It is sympathetically maintained
(D) It is less severe than previously thought
(E) It will not respond well to spinal cord
stimulation

Answer

A

(C) We do not know if it is sympathetically
mediated (B) from the block since this does not
provide evidence of etiology. We do not know
the involvement of vascularity since the block
is affecting sympathetic outflow and precludes
vascular evidence (which could be mediated by
a host of other physiologic events). There is no
clinical evidence to support a less severe case (D)
and, the evidence suggests that it will respond
to spinal cord stimulation (E).

Question 17

Q

348. Neuropathic pain can result in which of the
following condition?
(A) Central sensitization
(B) Allodynia
(C) Hyperalgesia
(D) B and C
(E) A, B, and C

Answer

A

(E) Central sensitization is the reason for many
of the symptoms including allodynia and
hyperalgesia. Therefore, all are correct.

Question 18

Q

Potential neurophysiologic mechanisms underlying
the development of neuropathic pain
include
(A) microglial activation in the spinal cord
(B) cytokine production in the spinal cord
(C) decreased glutamate release in the
spinal cord
(D) A and C
(E) A and B

Answer

A

(E) Cytokines are inflammatory mediators
released by a variety of cells that regulate the
inflammatory response. Systemic or local injection
of cytokines in animal models causes mechanical
and thermal hyperalgesia. Cytokines may cause
excitation of nociceptors via the release of other
mediators, like prostaglandins. At the level of the
CNS, cytokines may be liberated by microglial
cells. The best studied excitatory amino acid is
glutamate. Glutamate may bind to ionotopic or
metabotropic glutamate receptors. Peripheral and
central activation of those receptors induces pain
behaviors in animals. All basic science evidence
suggests (A) and (B), but does not suggest (C).

Question 19

Q

350. When the stimulus of light touch exerts pain
which of the following is exhibited?
(A) Hyperalgesia
(B) Allodynia
(C) Hypereflexemia
(D) Paresthesia
(E) Hypertouchemia

Answer

A

(B) Following tissue damage, there is a decrease
of the threshold for noxious stimuli (hyperalgesia),
which may be associated to perception of
pain to normally innocuous stimuli. This phenomenon
is termed allodynia. Allodynia is most
likely caused by plastic changes at the level of the
primary sensory fibers and spinal cord neurons.

Question 20

Q

351. Phantom pain refers to
(A) any sensation of the missing limb,
except pain
(B) painful sensations referred to the
missing limb
(C) spontaneous movement of the stump
ranging from small jerks to visible
contractions (jumpy stump)
(D) pain referred to the amputation stump
(E) B and D

Answer

A

(B) Phantom sensation: any sensation of the
missing limb, except pain (A).
Stump contractions: spontaneous movement
of the stump ranging from small jerks to
visible contractions (jumpy stump) (C).
Stump pain: pain referred to the amputation
stump (D).

Question 21

Q

A 74-year-old male has a left lower extremity
amputation after a long bout with uncontrolled
diabetes mellitus (DM). What are the chances
that this patient will develop phantom pain?
(A) 33%
(B) 49%
(C) 55%
(D) 90%
(E) 75%

Answer

A

(E) While ranges between 2% and 88% are
quoted in the literature, most current studies state that between 60% and 80% of patients
will develop phantom pain after amputation.

Question 22

Q

A vascular surgeon consults the pain team on
a patient who is scheduled to undergo an
amputation secondary to peripheral vascular
disease. The patient has read about phantom
pain on the Internet and would like to know
when it would likely start. You tell the vascular
surgeon that
(A) the onset of phantom pain is usually
within the first week after amputation
(B) most studies have shown that phantom
pain will start between 2 and 4 weeks
after an amputation for peripheral
vascular disease
(C) the likelihood of her developing
phantom pain in the first 6 months after
amputation is low, but increases drastically
between 6 and 9 months
(D) the onset will likely be delayed for years
(E) none of the above

Answer

A

(A) Prospective studies in patients undergoing
amputation mainly because of peripheral vascular
disease have shown that the onset of
phantom pain is usually within the first week
after amputation.
However, in a retrospective study of individuals
who were congenital amputees or
underwent amputation before the age of 6 years,
Melzack and coworkers found that the mean
time for onset of phantom limb pain was 9 years
in the group of congenital amputees and 2.3 years
in the group of individuals with early amputations.
[Jensen TS, Krebs B, Nielsen J, et al.
Phantom limb, phantom pain, and stump pain
in amputees during the first 6 months following
limp amputation.

Question 23

Q

The patient mentioned in the previous question
develops early and severe phantom pain:
(A) The patient is more likely to suffer from
long-standing pain
(B) The patient is less likely to suffer from
long-standing pain
(C) The patient is more likely to suffer incapacitating
pain for 1 year that will
subside rather abruptly
(D) It is likely that the patient will develop
neuropathic pain in the extremity
contralateral to the amputation
(E) The pain will likely be refractory to
treatment with anticonvulsants

Answer

A

(A) Patients who develop early and severe
phantom pain are more likely to suffer from
chronic pain, whereas individuals who are
pain-free at the beginning are less likely to
develop significant pain. However, prospective
studies with a maximum follow-up period of
2 years suggest that phantom pain may diminish
with time.

Question 24

Q

355. The number of amputees who have severe
phantom limb pain is
(A) 20% to 30%
(B) 60% to 80%
(C) 5% to 10%
(D) 1% to 2%
(E) 45% to 55%

Answer

A

(C) While phantom limb pain is seen in 60% to 80% of amputees, only 5% to 10% have severe pain.

Question 25

Q

Preamputation pain
(A) is more likely to lead to phantom pain if
the amputation is traumatic
(B) may sensitize the nervous system,
explaining why some individuals may
be more susceptible to development of
chronic phantom pain
(C) is more likely to lead to phantom pain if
the amputation is secondary
(D) is similar in character and localization to
the subsequent phantom pain in 80% of
patients
(E) is less likely to lead to phantom pain if the
amputation is in the upper extremities

Answer

A

(B) Some retrospective studies, but not all have
pointed to preamputation pain as a risk factor
for phantom pain. It has been hypothesized that
preoperative pain may sensitize the nervous
system, explaining why some individuals may
be more susceptible to development of chronic
pain.
A. It has been noted that patients with traumatic
amputations, who had no pain prior
to the amputation, develop pain to the same
extent as patients with preoperative pain
who endure amputations after significant
medical pathology.
C. There is no correlation between the development
of phantom pain and whether the
amputation was primary or secondary.
Primary amputation is when the limb is lost
at the time of the injury. Secondary amputation
is when the limb is surgically removed
in a hospital.
D. Phantom pain may mimic preamputation
pain in both character and localization.
Preamputation pain may persist in some
patients, but it is not the case in the majority
of patients.
E. Site of amputation has not been found to
have a role in determining whether preamputation
pain leads to phantom pain.

Question 26

Q

A 25-year-old left lower extremity amputee
returns from Iraq. He experiences phantom
pain, but is attempting to move forward in life.
To ease his transition back into society which of
the following is the next best step?
(A) He should take as long as possible to
grieve before he finds new employment
(B) He should initially use a cosmetic
prosthesis before embarking on the task
of learning to use a functional one
(C) He should absolutely refuse to ever
have spinal anesthesia as it may worsen
phantom pain
(D) He should learn coping strategies as
phantom pain is a psychological
disturbance
(E) None of the above

Answer

A

(E)
A. Amputees who experienced a long delay
between the amputation and return to
work, had difficulty in finding suitable
jobs, and had fewer opportunities for
promotion.
B. The use of a functionally active prosthesis
as opposed to a cosmetic prosthesis may
reduce phantom pain.
C. Spinal anesthesia in amputees may precipitate
transient, difficult to treat phantom
pain. Given the low incidence of recurrent
phantom limb pain with spinal anesthesia,
its transient nature, and the fact that it can
be treated if it occurs, it has been concluded
that spinal anesthesia is not contraindicated
in patients with previous
lower limb amputation.
D. While there is no evidence that phantom
pain represents a psychological disturbance,
it may be triggered and precipitated
by psychosocial factors. It has been shown
that coping strategies are important for the
experience of phantom pain Research has
indicated that the way individuals cope
with pain may influence pain, and physical
and psychological adjustment.

Question 27

Q

Stump pain and phantom pain are often
confused. There are, however, notable differences.
Which of the following is true?
(A) Unlike phantom pain, stump pain
occurs in the body part that actually
exists, in the stump that remains
(B) Stump pain typically is described as a
“sharp,” “burning,” “electric-like,” or
“skin-sensitive” pain
(C) Stump pain is usually caused by a
neuroma
(D) Surgical revision of the stump or
removal of the neuroma is sometimes
considered when treating stump pain
(E) All of the above

Answer

A

(E) Stump pain is located at the end of an amputated
limb’s stump. Unlike phantom pain, it
occurs in the body part that actually exists, in the
stump that remains. It typically is described as
a “sharp,” “burning,” “electric-like,” or “skinsensitive”
pain. Some patients have spontaneous
movements of the stump, ranging from slight,
hardly visible jerks to severe contractions.
Stump pain results from a damaged nerve
in the stump region. Nerves damaged in the
amputation surgery try to heal and may form
abnormally sensitive regions, called neuromas.
A neuroma can cause pain and skin sensitivity.
Percussion of neuromas may increase
nerve fiber discharge and augmentation of
stump and phantom pain.
No one treatment has been shown to be
effective for stump pain. Because it is a pain
caused by an injured peripheral nerve, drugs
used for nerve pain may be helpful.
If the stump pain affects a limb, revision
of the prosthesis is sometimes beneficial.
Other approaches also are tried in selected
cases, including: nerve blocks, transcutaneous
electrical nerve stimulation, surgical revision
of the stump, or removal of the neuroma (this
procedure may fail because the neuroma can
grow back; some patients actually get worse
after surgery), and cognitive therapies.
Stump pain is common in the early postamputation
period. Stump pain can also persist
beyond the stage of postsurgical healing.
Stump pain and phantom pain are strongly
correlated. Phantom pain subsides with resolution
of stump pain and that it is more prevalent
in patients with phantom pain than in
those without it.
Careful sensory examination of amputation
stumps may reveal areas of sensory abnormalities
such as hypoesthesia, hyperalgesia, or allodynia.
However, a correlation between phantom
pain and the extent and degree of sensory abnormality
has not been established.

Question 28

Q

A neuroma is an inflammation of a nerve that
is seen universally after a nerve has been cut
(ie, during an amputation). They show spontaneous
and abnormal evoked activity following
mechanical or chemical stimulation from
the periphery. This results from
(A) an increased and novel expression of
sodium channels
(B) hyperexcitability changes and
reorganization of the thalamus
(C) an increase in potassium efflux
(D) increased activity in afferent C fibers
(E) A and D

Answer

A

(E) The ectopic and increased spontaneous and
evoked activity from the periphery is assumed
to be the result of an increased and also novel
expression of sodium channels.
Local anesthesia of the stump may reduce
or abolish phantom pain temporarily.
Decreasing peripheral output by locally anesthetizing
stump neuromas with lidocaine
reduced tap-evoked stump pain. On the other
hand, there was a clear increase in pain when the potassium channel blocker, gallamine was
injected in the perineuromal space. Both findings
support the premise that abnormal input
from peripheral nociceptors plays a role in
pain generation.

Question 29

Q

Some amputees show an abnormal sensitivity
to pressure and to repetitive stimulation of the
stump, which can provoke attacks of phantom
pain. Which of the following is the case in
humans?
(A) It can be reduced by giving the NMDA
antagonist, ketamine
(B) It can only be reduced by terminating
the stimulation
(C) It can be attributed to the general
excitability of spinal cord neurons,
where only C fibers gain access to
secondary pain-signaling neurons
(D) Sensitization of the dorsal horn may be
mediated by glycine and serotonin
(E) All of the above

Answer

A

(A) The pharmacology of spinal sensitization
entails an increased activity in NMDA
receptor–operated systems, and many aspects
of the central sensitization can be reduced by
NMDA receptor antagonists In amputees, the
evoked pain from repetitive stimulation can be
reduced by the NMDA antagonist ketamine
B. Terminating the stimulation is not the only
way to reduce the pain.
C. After a nerve is injured, there is an increase
in the general excitability of spinal cord
neurons, where C fibers and A-δ afferents
gain access to secondary pain-signaling
neurons.
D. Sensitization of dorsal horn neurons is
mediated by release of glutamate and neurokinin.
This sensitization may present in
several ways including: lowered threshold,
increased persistent neuronal discharges
with prolonged pain after stimulation, and
expansion of peripheral receptive fields.
The central sensitization may also be a
result of a different type of anatomical reorganization.
Substance P is normally expressed
in small afferent fibers, but following nerve
injury, it may be expressed in large A-β fibers.
This phenotypic switch of large A-β fibers into
nociceptive-like nerve fibers may be one of
the reasons why nonnoxious stimuli can be
perceived as painful

Question 30

Q

361. Of the following, which does not play a role in
the mechanism for generating phantom pain?
(A) Peripheral sensitization
(B) Central sensitization
(C) Cortical reorganization
(D) Increased thalamus response to
stimulation
(E) Sympathetic inhibition

Answer

A

(E)
E. The sympathetic nervous system may play
a role in generating and, in uparticular, in
maintaining, phantom pain.
After limb amputation and deafferentation
in adult monkeys, there is reorganization of the
primary somatosensory cortex, and while these
changes may be unique to the cortex, they may
also be, at least in part, the result of changes at
the level of the thalamus and perhaps even
brain stem or spinal cord. After dorsal rhizotomy,
the threshold to evoke activity in the
thalamus and cortex decreased, and the mouth
and chin invade cortices corresponding to the
representation of arm and fingers that have lost
their normal afferent input. In humans similar
reorganization has been observed. In the thalamus,
neurons that normally do not respond to
stimulation in amputees begin to respond and
show enlarged somatotropic maps. A cascade
of events seems to be involved in generating
phantom pain and it starts in the periphery,
spinal cord, brain stem, thalamus, and finally
ends in the cerebral cortex.

Question 31

Q

Pharmacologically treating phantom pain is
not easy. Which of the following medications
has not proven to be effective in well-controlled
trials?
(A) Tramadol
(B) Gabapentin
(C) Memantine
(D) Amitriptyline
(E) A and C

Answer

A

(C)
A. and D. Tramdol and amitriptyline have been
found to be efficacious in treating phantom
and stump pain in treatment naive patients.
B. Gabapentin has been noted to be better
than placebo in reducing phantom pain.
Failure to pharmacologically provide pain
relief should not be accepted until opioids
have been tried. Intravenous (IV) and oral
morphine have been shown to decrease phantom
pain. Case reports have indicated that
methadone may also be helpful.
Other trials have not reported the same
the success with an oral NMDA antagonist,
memantine.
Suggestions for the treatment of postamputation
pain (no evidence) (Note: it is important
to differentiate between early postoperative
pain and chronic pain [pain persisting more
than 4 weeks], and stump and phantom pain):
Early postoperative pain
Stump pain
Conventional analgesics
• Acetaminophen
• NSAIDs
• Opioids
+/− combined with epidural pain treatment
Stump and phantom pain
If neuropathic pain clearly exists (paroxysms
or abnormal stump sensitivity)—trial
with TCAs or anticonvulsants.
Chronic pain
Stump pain
• Local stump surgery: if obvious stump
pathology is present, revisions should be
considered; surgery should be avoided in
cases of sympathetically maintained pain.
• Local medical treatment: topical lidocaine or
capsaicin can be tried in those who have
stump pain but no obvious stump pathology.
Stump and phantom pain (medical treatment,
in order of preference)
• Gabapentin 1200 to 2400 mg/d, slow titration.
Max dose of 3600 mg/d.
• TCAs (imipramine, amitriptyline, nortriptyline)
100 to 125 mg/d, slow titration. Check
electrocardiogram (ECG) before starting.
Monitor plasma levels with dose greater
than 100 mg/d. If sedation is wanted,
amitriptyline should be used.
• If the pain is mostly paroxysmal, lancinating,
or radiating:
• Oxcarbazepine 600 to 900 mg/d. Start at
300 mg and increase by 300 mg daily.
• Carbamazepine 450 mg/d. Start dose
150 mg, daily increments of 150 mg.
Monitor plasma levels after 10 days on
maximum dose.
• Lamotrigine 100 to 200 mg/d. Start dose
25 mg/d, slow titration with increments
of 25 mg/14 days (to avoid rash).
• Opioids (long-acting) or tramadol.
• If none of the above has an effect, refer the
patient to the pain clinic.
• In pain center: can perform IV lidocaine
trial or ketamine trial. If the lidocaine test is
positive—reconsider anticonvulsants. If the
ketamine test is positive: consider memantine
or amantadine.
Physical therapy encompassing massage,
manipulation, and passive range of motion
may prevent trophic changes and vascular
congestion in the stump. Transcutaneous electrical
nerve stimulation, acupuncture, ultrasound,
and hypnosis, may have a beneficial
effect on stump and phantom pain.

Question 32

Q

363. A65-year-old Vietnam War veteran with a left
below the knee amputation and phantom pain
has surgery on an amputation neuroma. He
should expect
(A) excellent resolution of his phantom pain
(B) short-term pain relief
(C) a likely infection and subsequent
complicated hospital course
(D) decreased pain only if he receives a
40-minute infusion of diphenhydramine
within 24 hours of the surgery
(E) none of the above

Answer

A

(B) Surgery on amputation neuromas and more
extensive amputation were accepted treatment modalities for stump and phantom pain in the
past. Today, stump revision is probably done
only in cases of obvious stump pathology, and
in properly healed stumps there is almost never
an indication for proximal extension of the
amputation because of pain. Surgery should
be avoided in cases of sympathetically maintained
pain. Surgery may produce short-term
pain relief but pain often reappears. The results
of other invasive procedures such as dorsal
root entry zone lesions sympathectomy and
cordotomy have generally been nontherapeutic,
and most of them have been abandoned.

Question 33

Q

Apatient has tingling sensations in a phantom
limb that are uncomfortable and annoying
but do not interfere with activities or sleep.
According to the Sunderland classification of
patients with phantom pain, what group is this
patient in?
(A) Group I
(B) Group II
(C) Group III
(D) Group IV
(E) None of the above

Answer

A

(B) Classification of patients with phantom
pain:
Group I: Mild intermittent paresthesias that
do not interfere with normal activity, work, or
sleep.
Group II: Paresthesias that are uncomfortable
and annoying but do not interfere with activities
or sleep.
Group III: Pain that is of sufficient intensity,
frequency, or duration to be distressful; however,
some patients in this group have pain
that is bearable, that intermittently interferes
with their lifestyle, and that may respond to
conservative treatment.
Group IV: Nearly constant severe pain that
interferes with normal activity and sleep.

Question 34

Q

365. The gate-control theory of pain has been used
to explain phantom limb pain. It states that
(A) following significant destruction of
sensory axons by amputation, wide
dynamic range neurons are freed by
inhibitory control
(B) self-sustaining neuronal activity may
occur in spinal cord neurons
(C) if spontaneous spinal cord neuronal
activity increases by any amount, pain
may occur in the phantom limb
(D) A and B
(E) A, B, and C

Answer

A

(D)
A. and B. The gate control theory of pain, put
forward by Ronald Melzack and Patrick
David Wall in 1962, and again in 1965, is the
idea that the perception of physical pain is
not a direct result of activation of nociceptors,
but instead is modulated by interaction
between different neurons, both paintransmitting
and non–pain-transmitting.
The theory asserts that activation of nerves
that do not transmit pain signals can interfere
with signals from pain fibers and
inhibit an individual’s perception of pain. It
has been used to explain phantom limb
pain. Following marked destruction of sensory
axons by amputation, wide dynamic
range neurons are freed by inhibitory control. Self-sustaining neuronal activity may then
occur in spinal cord neurons.
C. If the spontaneous spinal cord neuronal
activity exceeds a critical level, pain may
occur in the phantom limb.
This loss of inhibitory control may lead to
spontaneous discharges at any level in the
CNS and may explain the lack of analgesia in
paraplegics with phantom body pain after
complete cordectomy Pain increases after
blocking conduction are in line with the theory,
as continued loss of peripheral sensory
input would lead to further disinhibition.
Sodium thiopental perpetuates CNS inhibition
and has been reported to end phantom
limb pain during spinal anesthesia. Melzack
R, Wall PD. Mechanisms: a new theory. Agate
control system modulates sensory input from
the skin before it evokes pain perception and
response. Science. 1965;150(3699).

Question 35

Q

All of the following are true about primary
dysmenorrhea, EXCEPT
(A) pain is transmitted via the thoracolumbar
spinal segments and pelvic afferents
(B) the etiology of pain includes myometrial
contractions leading to intense intrauterine
pressure and uterine hypoxia
(C) prostaglandins and leukotriene production
that sensitizes afferent pelvic nerves
is part of its pathogenesis
(D) endometriosis and adenomyosis are its
most common causes
(E) altered central receptivity of the afferent
input from the pelvis is thought to be
relevant in its development

Answer

A

(D) Primary dysmenorrhea is defined as
menstrual pain without pelvic pathology.
Endometriosis and adenomyosis are the most
common causes of secondary dysmenorrhea.

Question 36

Q

367. All of the following are true about chronic
endometriosis, EXCEPT
(A) ovaries, cul-de-sac, uterine tubes, surface
of the bowel are among the most common
sites of pathologic implantation of
the functioning endometrial tissue
(B) retrograde menstruation, lymphatic
spread, and hematogenous spread of the
endometrial tissue are all thought to
play a role in endometriosis etiology
(C) pain occurs only with menses
(D) definitive diagnosis can be made by visualization
of the characteristic lesions without
a mandatory histologic confirmation
(E) leuprolide acetate (Lupron) may be an
effective treatment of the symptoms of
chronic endometriosis

Answer

A

(C) The pain of endometriosis can occur with
menses or sexual intercourse or can always be
present. It can also mimic any known pelvic
pathology. Answers A, B, D, and E are all correct.

Question 37

Q

All of the following are correct, EXCEPT
(A) pudendal nerve takes origin from S2, S3,
and S4 roots bilaterally
(B) bilateral denervation of the inferior
hypogastric nerves is as effective as a
lumbar epidural block with respect to
sensory input from the uterus and cervix
(C) many patients with hymenal neuropathy
are so emotional and complain so
violently that the pelvic examination is
not possible
(D) patients with sympathetic pelvis syndrome
have a deep pain in the pelvis
not associated with physically
detectable abdominal wall or muscle
tenderness
(E) ilioinguinal and iliohypogastric neuropathy
is rarely associated with the surgeries
in the lower abdominal wall area

Question 38

Q

All of the common reasons for the inadequate
management of acute pain in a hospital setting
are true, EXCEPT
(A) the common idea that pain is merely a
symptom and not harmful in itself
(B) the fact that opioids have no potential
for addiction when administered strictly
for acute pain
(C) lack of understanding of the pharmacokinetics
of various agents
(D) lack of appreciation of variability in
analgesic response to opioids
(E) prescription of inappropriately low
doses of opioids and thinking that
opioids must not be given more often
than every 4 hours

Answer

A

(B) Opioids have the potential for addiction
even when administered for acute pain.
However, it is the exaggerated common fear
of the potential for addiction to opioids that
often interferes with adequate pain management.
The rest of the answers are correct.

Question 39

Q

The following are true about pathologic
(nonphysiological) pain, EXCEPT
(A) it occurs in the context of central
sensitization
(B) it occurs in the context of peripheral
sensitization
(C) it outlasts the stimulus
(D) it spreads to nondamaged areas
(E) it is elicited by A-δ and C fibers, but not
A-β fibers, which transmit touch sensation

Answer

A

(E) It is recognized that long-term changes
occur within the peripheral and central nervous
system following noxious input. This neuroplasticity
alters the body’s response to usual
peripheral sensory input. In pathologic pain
conditions, stimulation of A-β fibers, normally eliciting response to touch, may elicit pain.

Question 40

Q

Perioperative administration of NSAIDs
(A) does not reduce the demand for opioids
during and after the surgery
(B) is contraindicated because of increased
possibility of bleeding
(C) has synergistic effect with opioids
(D) has its analgesic effect only through
peripheral mechanisms
(E) is not associated with the concerns for
postoperative bleeding

Answer

A

(C) Even though there have been some concerns
regarding the risks of perioperative NSAIDs, including intra- and postoperative bleeding,
they continue to have a useful role. Combination
of NSAIDs and opioids has a synergistic
analgesic effect, as they act at the different sites
of pain pathways. More new evidence is emerging
that NSAIDs exert their analgesic effects also
through the central mechanisms.

Question 41

Q

372. All of the following are true about the NMDA
receptors, EXCEPT
(A) they are involved in development of
“windup” facilitation
(B) NMDA agonists reduce development of
tolerance to opioids
(C) NMDA receptors are involved in
development of central sensitization
(D) NMDA receptors are involved in
changes of peripheral receptive fields
(E) NMDA receptors are involved in
induction of oncogenes and long-term
potentiation

Answer

A

(B) It has been demonstrated that the administration
of an NMDA antagonist reduces the
development of tolerance to morphine. The rest
of the answers are correct.

Question 42

Q

As compared with somatic pain, all of the following
are true about visceral pain, EXCEPT
(A) it may follow the distribution of a
somatic nerve
(B) it is dull and vague
(C) it is often periodic and builds to peaks
(D) it is often associated with nausea and
vomiting
(E) it is poorly localized

Answer

A

(A) The following are the usual features of the
somatic pain: well localized, sharp and definite,
often constant (sometimes periodic); it is rarely
associated with nausea usually when it is deep
somatic pain with bone involvement; it may be
following the distribution of a somatic nerve.
In contrast, the visceral pain: is poorly localized,
diffuse, dull, and vague; it is often periodic and
builds to peaks (sometimes constant); it is often
associated with nausea and vomiting.

Question 43

Q

374. The following statements are true regarding
preemptive analgesia, EXCEPT
(A) preemptive analgesia is helpful in
reducing postoperative pain in part by
reducing the phenomenon of central
sensitization
(B) early postoperative pain is not a significant
predictor of long-term pain
(C) local anesthetics, opioids, and NSAIDs
can be used for preemptive analgesia
(D) preemptive analgesia may have the
potential to prevent the development of
chronic pain states
(E) preemptive analgesia is thought to
reduce neuroplastic changes in the
spinal cord

Answer

A

(B) It has been demonstrated that early postoperative
pain is a significant predictor of longterm
pain. The rest of the answers are correct.

Question 44

Q

The following statements are true regarding
multimodal analgesia, EXCEPT
(A) it may include NSAIDs, acetaminophen,
local anesthetics, and opioids in the
same patient
(B) it is beneficial because of the synergistic
action of the individual medications
with different sites of action along the
pain pathways
(C) it is not very valuable owing to an
increase in the incidence of side effects
(D) it facilitates early mobilization of the
postsurgical patient
(E) it expedites return to normal parenteral
nutrition

Answer

A

(C) Multimodal analgesia makes it possible to
significantly reduce the total consumption of
opioids intra- and postoperatively. Therefore,
opioid side-effects are minimized, including
inevitable opioid-induced GI stasis that delays
the resumption of normal enteral nutrition after
surgery.

Question 45

Q

376. All of the following statements about PHN are
correct, EXCEPT
(A) midthoracic dermatomes is one of the
most common sites for PHN
(B) men are affected more often than
women in a ratio of 3:2
(C) ophthalmic division of the trigeminal
nerve is one of the most common sites
for PHN
(D) PHN may occur in any dermatome
(E) PHN has an incidence of 9% to 14.3%

Answer

A

(B) PHN affects women more often than men, in a ratio of approximately 3:2. The rest of the answers are correct.

Question 46

Q

377. PHN is defined as
(A) any pain associated with the herpes
zoster
(B) pain caused by herpes zoster for more
than 1 month
(C) persistent pain with a significant
neuropathic component in a dermatomal
distribution
(D) pain caused by herpes zoster for more
than 3 months
(E) neuropathic pain in midthoracic dermatomes
caused by herpes simplex virus

Answer

A

(B) PHN is defined as pain caused by herpes zoster for more than 1 month.

Question 47

Q

378. Which of the following is true about the management
of PHN?
(A) Approximately 40% of patients with
PHN have either incomplete or no relief
from treatment
(B) Prevention of herpes zoster is not nearly
as important as a multimodal treatment
of PHN
(C) Current multimodal treatment of PHN
is nearly 100% effective, independent of
the duration of the symptoms
(D) Current multimodal treatment of PHN
is nearly 100% effective as long as it is
started within the first month of the
symptoms of PHN
(E) Current multimodal treatment of PHN
is nearly 100% effective as long as it is
started immediately after the first
symptoms of herpes zoster

Answer

A

(A) As many as 40% of patients with PHN have
either incomplete or no relief from treatment.
Because of this, the future may lie with prevention
through vaccination and early aggressive treatment
of herpes zoster with antivirals and analgesics
to reduce the extent of the nerve damage
and sensitization that may correlate with PHN.

Question 48

Q

The following are true about the use of antidepressants
in treatment of PHN, EXCEPT
(A) amitriptyline has been shown to be
effective in treatment of PHN, but has
significant limitations in the long term
because of its side effects
(B) selective serotonin reuptake inhibitors
(SSRIs) have been found to be equally or
more effective in treatment of PHN than
the older generation of tricyclic antidepressants
(TCAs) or selective norepinephrine
reuptake inhibitors (SNRIs)
(C) SNRIs have been shown to be more effective
than placebo in treatment of PHN
(D) antidepressant therapy in PHN is built
on sound, scientific basis
(E) one of the significant side effects of
TCAs is their anticholinergic properties

Answer

A

(B) Experience with serotonergic antidepressants,
such as clomipramine, trazodone, nefazodone,
fluoxetine, and zimelidine, in PHN
has been disappointing. The evidence supporting
the use of noradrenergic agents is more
compelling. The rest of the answers are correct.

Question 49

Q

Which of the following is true about use of
opioids in the treatment of PHN?
(A) The use of opioids is not justified for
nonmalignant pain
(B) Opioids tend to be less effective for the
treatment of neuropathic pain than
nonneuropathic pain
(C) Opioids were not found to be useful in
the treatment of PHN
(D) The use of opioids should be avoided in
combination with antidepressants
because of the risk of excessive central
nervous system (CNS) suppression
(E) The use of opioids in PHN should be
avoided owing to the increased
potential of addiction

Answer

A

(B) There has been evidence that opioids do not relieve neuropathic pain as well as nonneuropathic pain. However, there is also evidence that opioids have been successfully used for the treatment of PHN.

Question 50

Q

381. Which of the following is the most common cause
of autonomic neuropathy in the developed
world?
(A) Leprosy
(B) Diabetes mellitus (DM)
(C) Human immunodeficiency virus (HIV)
infection
(D) Heavy metal poisoning
(E) Idiopathic etiology

Answer

A

(B) DM is the most common cause of autonomic
neuropathy, and peripheral neuropathy
in general, in the United States, as well as in the
rest of the developed world. Leprosy is the
most common cause of peripheral neuropathy
in the world.

Question 51

Q

Diabetic amyotrophy
(A) has a poor prognosis
(B) has better prognosis when it involves
upper extremities
(C) usually resolves within 1 to 2 years
spontaneously
(D) has better prognosis when the symptoms
do not involve pain
(E) it is directly related to hyperglycemia

Answer

A

(C) Diabetic amyotrophy starts with pain and
involves the lower extremities. It has a good
prognosis and usually resolves spontaneously
in 12 to 24 months. It is not directly related to
hyperglycemia.

Question 52

Q

383. The following are true about the distal sensorimotor
polyneuropathy, EXCEPT
(A) it is the most common neuropathic
manifestation of both type 1 and type 2
diabetes
(B) it starts distally and spreads proximally
(C) initial symptoms may involve
numbness and tingling in the toes or
feet
(D) it is a length-dependent neuropathy
(E) it is usually asymmetrical

Answer

A

(E) Distal sensorimotor polyneuropathy is a
symmetrical length-dependent process with
dying-back or dropout of the longest nerve
fibers—myelinated and unmyelinated. All
other answers are correct.

Question 53

Q

The prevalence of diabetic neuropathy in DM patients is
(A) less than 1% at diagnosis of DM, rising
to 10% in patients diagnosed for longer
than 5 years
(B) about 10% at diagnosis of DM, rising to
more than 50% in patients diagnosed for
longer than 5 years
(C) about 50% at diagnosis of DM, rising to
almost 100% in patients diagnosed for
longer than 5 years
(D) about 50% at diagnosis of DM, and does
not change significantly with time
(E) no such studies have been done so far

Answer

A

(B) It is generally agreed that the prevalence of
neuropathy is about 10% at diagnosis of DM,
rising to 50% or more in patients diagnosed for
longer than 5 years

Question 54

Q

Patients with diabetic distal sensorimotor
polyneuropathy initially may complain of
numbness and tingling in the toes or feet,
which then slowly spreads proximally over
months to years. Eventually, numbness and
tingling appear in the fingertips, as the symptoms
of diabetic polyneuropathy progress to
(A) ankle
(B) knee
(C) mid-thigh
(D) buttock and groin
(E) abdomen

Question 55

Q

Which of the following is the most widely
accepted cause of trigeminal neuralgia?
(A) Demyelinating conditions, as trigeminal
neuralgia is most common in patients
with multiple sclerosis
(B) Direct trauma of the trigeminal ganglion
at the level of the foramen ovale, before
branching into its three branches
(C) Arterial cross-compression of the
trigeminal nerve in the posterior fossa
(D) Tumors of the posterior fossae
(E) Poor vascular supply to the affected
trigeminal branch

Answer

A

(C) It is accepted that the most common cause
of trigeminal neuralgia is arterial crosscompression
of the trigeminal nerve in the posterior
fossa, as suggested by Jannetta in 1982.
Electron microscopy of trigeminal nerve biopsies
taken from patients with trigeminal neuralgia
has shown areas of axonal swelling and demyelination
adjacent to the area of arterial compression.
Although trigeminal neuralgia is more
common in patients with multiple sclerosis,
only a small portion of patients with trigeminal neuralgia suffer from multiple sclerosis and
does not explain the majority of the cases.

Question 56

Q

Which of the following is true regarding medical
management for the treatment of trigeminal
neuralgia?
(A) Anticonvulsant medications are usually
considered as the second line of treatment
(B) Beneficial effects of carbamazepine are
better in elderly patients
(C) Risk of side effects of carbamazepine
increase with age
(D) Carbamazepine has proven to be the
most effective treatment for trigeminal
neuralgia, independently of the sideeffect
profile
(E) Because of the unlikelihood of serious
side effects with surgery, all patients
should consider this option first

Answer

A

(C) Carbamazepine is likely to be beneficial in
up to 70% of the patients. Incidence of side effects
is often higher in elderly patients especially if the
drug escalation is too fast. Allergic rash is seen in
up to 10% of the patients and high concentration
of the drug may be associated with fluid retention
promoting cardiac problems. Carbamazepine is a
potent hepatic enzyme inducer which can potentially
lead to undesirable drug-to-drug interactions.
Although microsurgical exploration of the
posterior fossa is the highly successful, it is a
major surgery with 0.5% risk of mortality and
major morbidity. The effectiveness of pimozide
for trigeminal neuralgia is better than carbamazepine,
but the high frequency of side effects
limits its clinical use.

Question 57

Q

The gasserian ganglion
(A) receives exclusively proprioceptive information
from the muscles of mastication
(B) the mandibular branch is located medial
to the ophthalmic branch
(C) the two medial branches are sensory
while the lateral branch is partially
motor
(D) the ganglion lies out of the cranium, in
the Meckel cave
(E) the foramen rotundum is used as landmark
for the blockage of the trigeminal
ganglion

Answer

A

(C) The trigeminal ganglion receives sensation
from the oral mucosa, scalp, nasal areas, face,
and teeth. Proprioceptive information is transmitted
into the ganglion from the mastication
and extraocular muscles. The peripheral
branches of the ganglion are the ophthalmic,
the maxillary, and the mandibular, which are
organized somatotropically, with the ophthalmic
branch located dorsally, the maxillary
branch is intermediate, and the mandibular
nerve is located ventrally. The gasserian ganglion
lies within the cranium, in the middle
cranial fossa. The posterior border of the ganglion
includes the dura of the Meckel cave. The
landmark to perform the trigeminal ganglion
block is the foramen ovale and not the foramen
rotundum.

Question 58

Q

Which of the following is true regarding the
diagnosis of trigeminal neuralgia?
(A) The diagnosis must be confirmed with
magnetic resonance imaging (MRI) to
detect vascular trigeminal nerve compression
(B) Sensory evoked potentials is the most
sensitive test to perform the diagnosis
(C) The diagnosis is clinical and tests are
only necessary to rule out associated
conditions
(D) To accurately diagnose the condition, it
is necessary to correlate clinical findings
with MRI and sensory evoke potential
tests
(E) None of the above

Answer

A

(C) The diagnosis of trigeminal neuralgia is
eminently clinical and further tests are necessary
only to rule out associated conditions.
When the condition is found, MRI and evoked
potential testing are strongly recommended to
rule out secondary causes. Clinically the onset of
trigeminal neuralgia is around the age of 50 years,
more common in females, almost exclusively
unilateral with a paroxysmal nature.

Question 59

Q

390. Giant cell arteritis is characterized by which of
the following?
(A) Affects almost exclusively Asian
population
(B) As other forms of vasculitis, giant cell
arteritis commonly involves skin,
kidneys, and lungs
(C) Males are more commonly affected
(D) It is more common in older patients,
with a peak incidence between 60 to
75 years of age
(E) Visual loss is the presenting symptom in
over 50% of the patients

Answer

A

(D) The giant cell arteritis affects almost exclusively
the white population although it can occur in worldwide. Unlike other forms of vasculitis
it rarely affects skin, kidneys, or lungs.
Females are affected 3 times more often than
males. Visual loss is now considered to affect
between 6% to 10% of patients in most series.

Question 60

Q

According to the International Headache
Society Diagnostic Criteria, analgesic rebound
headache is
(A) headache that resolves or reverts within
2 weeks after discontinuation of the suspected
medication
(B) headache that worsens after intake of
analgesics and reduces in intensity and
frequency with reduction in the analgesic
dose
(C) the intensity of the headache decreases
in intensity proportionally to the
decrease in the dose of analgesic
(D) headache greater than 15 days per
month that has developed or markedly
worsened during medication overuse
(E) headache that increases in intensity with
the use of morphine, most likely
because of the cerebral vasodilation
mediated by histamine release

Answer

A

(D) Analgesic rebound headache resolves or
reverts to its previous pattern within 2 months
of discontinuing of the overused medication.

Question 61

Q

Cluster headaches are characterized by
(A) lancinating unilateral headache that is
commonly triggered by stress factors
(B) the pain is strictly unilateral and autonomic
symptoms occur ipsilateral to the
pain
(C) the onset is slow with progressive worsening
of the pain over several hours
with an attack usually lasting 3 to
4 days
(D) melatonin is commonly indicated as
therapy for the acute attack
(E) cluster headaches are more common in
elderly patients

Answer

A

(B) The first statement better describes trigeminal
neuralgia. Cluster headache affects more
males than females with a 5:1 ratio and can
begin at any age. Attacks are severe, stabbing,
screwing, unilateral pain, occasionally preceded
by premonitory symptoms, with sudden
onset, and rapid crescendo. Therapeutic interventions
for the acute attack include oxygen,
triptans, dihydroergotamine, ketorolac, chlorpromazine,
or intranasal lidocaine, cocaine, or
capsaicin. Melatonin has been found to be
moderately effective as a preventive treatment
in episodic and chronic cluster headache

Question 62

Q

Which of the following describes the pathophysiologic
changes seen in migraine?
(A) Inflammation of hypothalamic structures
leads to low threshold stimulation
of vascular and meningeal tissues
(B) Central sensitization mediated by attribution
to activation of β-fibers in the
trigeminal system, mediates extracranial
hypersensitivity
(C) Large cerebral vessels, pial vessels, large
sinuses, and the dura, are innervated by
fibers originating from the sphenopalatine
ganglion
(D) Activation and threshold reduction of
the trigeminocervical complex by its
most caudal cells
(E) In acute attacks, a marked reduction in
vasoactive substances, including substance
P, calcitonin gene related peptide (CGRP),
and nitric oxide is commonly seen

Answer

A

(D) Sterile neurogenic inflammation is often
seen after stimulation of the trigeminal ganglion,
which innervates large cerebral vessels,
pial vessels, large sinuses, and the dura via
unmyelinated C fibers. In acute attacks of
migraine, substance P, CGRP, and nitric oxide
mediate the neurogenic inflammation

Question 63

Q

394. Which of the following is correct regarding
headache?
(A) Migraine is the most common form of
headache
(B) Tension-type headache (TTH) is commonly
aggravated by physical exercise
(C) The presence of nausea, vomiting,
photophobia, or phonophobia excludes
the diagnosis of TTH
(D) The most common form of migraine is
associated with aura
(E) Comorbid conditions associated with
chronic migraine include depression,
anxiety, and panic disorders

Answer

A

(E) TTH is the most common type of headache.
Aura is present in only 20% of patients suffering
from migraine. Although chronic daily
headache diagnostic criteria for probable TTH
requires no nausea or vomiting as one of the
criteria or absence of photophobia, or phonophobia,
nausea may be seen in 4.2% of patients
with TTH, while phonophobia is reported in
10.6% of them.

Question 64

Q

Hundred precent oxygen inhalation is a safe
and effective method for acute treatment of
(A) chronic daily headache
(B) TTH
(C) migraine with aura
(D) cluster headache
(E) glossopharyngeal neuralgia

Answer

A

(D) Inhalation of 100% oxygen at 7 to 12 L/min
is effective in treating the majority of cluster
headache sufferers when used continuously
for 15 to 20 minutes. Generally oxygen inhalation
is not considered to be effective in any
other form of primary neurovascular headache.

Answer 63

A

(C) PDPH and SIH are two distinct clinical entities
with similar presentation. The headache is
always bilateral, located in the occipital and/or
frontal area. Although low CSF pressure is
often noted, it is not necessary to confirm the
diagnosis.

Answer 64

A

(C) New daily persistent headache is a chronic,
unremitting headache of sudden onset, daily
pattern. The duration of the headache should be
at least 3 months. Some important features
include its moderate severity, bilateral location,
and lack of nausea, vomiting (N/V), photophobia,
and phonophobia (P/P). On the other hand,
status migrainosus is a severe debilitating
migraine, associated with N/V, P/P, and with
duration longer than 72 hours but that typically
do not exceed 2 weeks. The other diagnoses are
not consistent with the symptoms.

Answer 65

A

(A) The previously known classic migraine
(migraine with aura) is preceded by visual aura
that starts 20 to 40 minutes before the migraine
and is characterized by spreading scintillations
reflecting a slow propagation of neuronal and
glial excitation emanating from one occipital
lobe. Cortical spreading depression (CSD) presents
with dramatic shifts in cortical steady
potential (DC), temporary increases in extracellular
ions and excitatory neurotransmitters
(glutamate), and transient raise, followed by
sustained decrease in cortical blood flow. The
vascular theory proposed that migraine with
aura is caused by intracranial cerebral vasoconstriction
and the headache by reactive
vasodilation. Despite that, the theory can not
explain the prodromal symptoms or why some
antimigraine medications are not effective.
Hormonal fluctuations and estrogen withdrawal
may explain the higher incidence of
migraine in female patients during their reproductive
years, but are not related to the presence
of aura. Cerebral idiopathic hypertension
is a form of headache of unknown etiology

Answer 66

A

(D) The published literature commonly states
that 80% to 90% of low back pain resolves in
about 6 weeks, irrespective of the administration
or type of treatment, with only 5% to 10%
of patients developing persistent back pain. Contrary to this assumption, actual analysis of
research evidence shows that chronic low back and neck pain persist 1 year or longer in 25% to 60% of adult and/or elderly patients.

Answer 67

A

(C) Based on evaluations utilizing controlled diagnostic
blocks, the prevalence of zygapophysial or
facet joint involvement has been estimated to be
between 15% and 45% in heterogeneous groups of
patients with chronic low back pain.

Answer 68

A

(E) The clinical picture of metastatic epidural
spinal cord compression is uniformly reported
as pain, weakness, sensory loss, and autonomic
dysfunction. Metastatic epidural spinal cord
compression initially presents with severe back
pain in 95% of cases. After weeks of progressive
pain, the patient may develop weakness, sensory
loss, autonomic dysfunction, and reflex
abnormalities. Bladder and bowel dysfunction
are rarely presenting symptoms, but may
appear after sensory symptoms have occurred.
The exception to this generalization develops
with compression of the conus medullaris,
which presents as acute urinary retention and
constipation without preceding motor or sensory
symptoms

Answer 69

A

(B) Patients with severe, persistent symptoms
(discogenic in origin) that have been confirmed
by other diagnostic evaluations do not need to
undergo further evaluation by discography.
Specific uses for discography include, but are
not limited to: further evaluation of demonstrably
abnormal discs to help assess the extent of
abnormality or correlation of the abnormality
with clinical symptoms (in case of recurrent pain
from a previously operated disc and a lateral
disc herniation); patients with persistent, severe
symptoms in whom other diagnostic tests have
failed to reveal clear confirmation of a suspected
disc as the source of pain; assessment of
patients who have failed to respond to surgical
procedures to determine if there is painful
pseudoarthrosis or a symptomatic disc in a posteriorly
fused segment, or to evaluate possible
recurrent disc herniation; assessment of discs
before fusion to determine if the discs within the
proposed fusion segment are symptomatic and
to determine if discs adjacent to this segment are normal; and assessment of minimally invasive
surgical candidates to confirm a contained disc
herniation or to investigate contrast distribution
pattern before intradiscal procedures.

Answer 70

A

(A) Gait disturbances are a feature of cervical
myelopathy, not radiculopathy. Other signs and
symptoms of cervical radiculopathy include
upper extremity sensory disturbances and muscle
weakness.

Answer 71

A

(D) Experimental studies have given support to
the hypothesis that blood flow and nutrition to
the disc are diminished in smokers, the pH of
the disc is lowered, disc mineral content is
lower, fibrinolytic activity is changed, and there
are increased degenerative changes seen in the
lumbar spine.

Answer 72

A

(B) There is strong evidence from randomized
controlled trials that bed rest is not effective
for treating acute low back pain.

Answer 73

A

(A) Narrowing of the intervertebral discs has
long been considered one of the signs of pathologic
aging of the lumbar spine, but recent data
has shown that notion to be untrue. Large-scale
postmortem analysis have shown lumbar disc
height and diameter to actually increase with
age. The anterior-posterior diameter increases
by about 10% in females and 2% in males. Disc
height has been shown to increase by about
10% in most lumbar discs.

Answer 74

A

(C) Radiculopathy is a condition in which conduction
within the axons of a spinal nerve or its
roots are blocked. It can result in numbness
and weakness secondary to conduction block
in sensory and motor neurons respectively.
Conduction blockade can be caused by compression
or ischemia. It is important to make
the distinction that radiculopathy does not
cause pain. It may, however, be associated with
pain.

Answer 75

A

(D) The major theoretical complications of corticosteroid
administration include suppression
of pituitary-adrenal axis, hypercorticism,
Cushing syndrome, osteoporosis, avascular
necrosis of bone, steroid myopathy, epidural lipomatosis, weight gain, fluid retention, and
hyperglycemia.

Answer 76

A

(A) Absolute contraindications to epidural
steroid injections include sepsis, infection at
injection site, therapeutic anticoagulation, and
patient refusal. Relative contraindications
include preexisting neurologic conditions, prophylactic
low-dose heparin, thrombocytopenia,
and uncooperative patients.

Answer 77

A

(B) L4-L5 disc herniation with L5 nerve root
involvement involves: pain over the sacroiliac
joint, hip, lateral thigh, and leg; numbness
over the lateral leg and first three toes; weakness
with dorsiflexion of great toe and foot;
difficulty walking on heels; possible foot
drop; and internal hamstring reflex diminished
or absent. Numbness over the medial
thigh and knee, and quadriceps weakness are
indicative of L3-L4 disc herniation with L4
nerve root involvement. Difficulty walking
on toes and lateral heel pain are common
with L5-S1 disk herniation involving the S1
nerve root.

Answer 78

A

(B) Fifteen percent of patients with chronic low

back pain have sacroiliac joint pain.

Answer 79

A

413 to 417. 413 (B); 414 (D); 415 (E); 416 (A); 417 (C)
Spondylolysis is an acquired defect that results
from a fatigue fracture of the pars interarticularis
(the part of the lamina that intervenes
between the superior and inferior articular
processes on each side). Spondylolisthesis is
the displacement of a vertebrae or the vertebral
column in relationship to the vertebrae below.
Kissing spines (also known as Baastrup disease)
affects the lumbar spinous processes.
Excessive lumbar lordosis or extension injuries
to the lumbar spine cause adjacent spinous
processes to clash and compress the intervening
interspinous ligament. This results in a
periostitis of the spinous process or inflammation
of the affected ligament. Radiculopathy is
a neurologic condition in which conduction
blocks the axons of a spinal nerve or its roots
that results in numbness and weakness.
Radicular pain is pain that arises as a result of
irritation of a spinal nerve or its roots.

Answer 80

A

(E) In managing lumbar radicular pain with
interlaminar lumbar epidural steroid injections,
the evidence is strong for short-term relief and
limited for long-term relief. In managing cervical
radiculopathy with cervical interlaminar
epidural steroid injections, the evidence is moderate.
The evidence for lumbar transforaminal
epidural steroid injections in managing lumbar
radicular pain is strong for short-term and moderate
for long-term relief. The evidence for cervical
transforaminal epidural steroid injections
in managing cervical nerve root pain is moderate.
The evidence is moderate in managing lumbar
radicular pain in post–lumbar laminectomy syndrome.
The evidence for caudal epidural steroid
injections is strong for short-term relief and moderate
for long-term relief, in managing chronic
pain of lumbar radiculopathy and post–lumbar
laminectomy syndrome.

Answer 81

A

(A) The sources of the nerve endings in the
lumbar discs are two extensive microscopic
plexuses of nerves that accompany the anterior
and posterior longitudinal ligaments. The nerve
plexuses that innervate intervertebral discs are
derived from the lumbar sympathetic trunks.
The dorsal rami supply innervation to the muscles
of the back and zygapophysial joints. In
normal lumbar intervertebral discs, nerve fibers
are only found in the outer third of the annulus
fibrosis. Discs painful on discography and
removed with operation have nerve growth
deep into the annulus and into the nucleus pulposus.
Disc fissuring is a trigger for neoinnervation
and neovascularization of a disc.

Answer 82

A

(A) Development of an epidural abscess is a
very rare complication of epidural steroid injections.
It needs to be recognized and treated
quickly to avoid irreversible injury. Symptoms
of an epidural abscess include severe back pain
that is followed by radicular pain 3 days later.
The initial back pain may not become evident
for several days after the injection.

Answer 83

A

(C) Plain x-rays are recommended for possible
fractures, arthropathy, spondylolisthesis, tumors,
infections, stenosis, and congential deformities.
CT images are recommended for bone/joint
pathologies, lateral disc herniations, stenosis
(ie, spinal canal, neuroforaminal, lateral recess),
and for those in which an MRI is contraindicated.
MRI is recommended for disc herniations,
spinal stenosis, osteomyelitis, tumors (ie, spinal
cord, nerve roots, nerve sheath, paraspinal soft
tissue), and cauda equine syndrome.

Answer 84

A

(D) The L2 nerve root is involved with hip flexion,
L3 with leg extension, L4 with heel walking,
L5 with first toe dorsiflexion (and heel
walking), and S1 with toe walking

Answer 85

A

(C) Laminotomy with discectomy has a low infection
rate, statistically. The most frequent complication
is a dural tear. Neural injury may occur as
a result of a dural tear and may cause long-term
pain and neurologic deficit. Recurrence of the
herniation occurs in approximately 5% of cases.
Infection and neural injury occurs in less than
0.5% of cases.

Answer 86

A

(C) Conservative treatment is usually the first
treatment of choice for patients presenting with
FBSS. It consists of medical management of
contributing factors (ie, depression, obesity,
smoking), rehabilitation, and behavior modification
(ie, alcohol or drug dependency).

Answer 87

A

(D) Many prognostic indicators have been
implicated in patients undergoing repeat lumbosacral
spine surgery. They may or may not be
significant for each patient and should be taken
into context for the particular patient. Women
have been found to have better outcomes than
men. Patients with a history of favorable outcomes
from prior surgeries tend to have better
outcomes as well. A history of few previous
surgeries, operative/myelographic findings of
disc herniation, and a history of working
immediately prior to surgery are all favorable
prognostic indicators. Less favorable prognostic
indicators include epidural scarring that
requires lysis of adhesions and pseudoarthrosis
of a prior fusion.

Answer 88

A

(E) Waddell signs are used to help diagnose
nonorganic low back pain complaints. Each of
the five findings is considered positive if present.
Three positive findings are considered highly
suggestive of a nonorganic source of pain:
Tenderness: does not follow dermatomal or
referral patterns and is hard to localize.
Stimulation testing: stimulating distant
sites should not cause discomfort.
Distraction testing: findings when testing the
same site are inconsistent when the patient’s
attention is distracted.
Regional disturbance: motor and sensory
testing yield nonanatomic findings.
Overreaction: inappropriate verbal remarks
or facial expressions, withdrawal from touch,

Answer 89

A

(B) Ankylosing spondylitis is characterized by
pain and stiffness in young males (typically
ages 17-35 years) more often than females. It is
worse in the morning and improves with mild
exercise. The pain will typically last for at least
3 months and be diffuse in nature affecting the
low back and spine. Rheumatoid arthritis is an
inflammatory polyarthritis that affects middleaged
women more often than men. It typically
presents with morning stiffness that improves
as the day progresses, and the spine is not
affected until late in the disease. Psoriatic
arthritis is characterized by inflammation of
the skin and joints that typically presents in
the fourth and fifth decades of life. Klippel-Feil
syndrome is a congenital disorder that is characterized
by abnormal fusion of two or more
bones in the cervical spine. Reiter syndrome is
a reactive arthritis that is characterized by a
triad of symptoms: nongonococcal urethritis,
conjunctivitis, and arthritis.

Answer 90

A

(C) The three major criteria for cervicogenic
headache include (1) signs and symptoms of
neck involvement (precipitation of head pain
by: neck movement and/or sustained awkward
head positioning, by external pressure over the
upper cervical or occipital region on the symptomatic
side; restriction of the range of motion in
the neck; ipsilateral neck, shoulder, or arm pain
of a rather vague nonradicular nature or, occasionally,
arm pain of a radicular nature); (2) confirmatory
evidence by diagnostic anesthetic
blockades; and (3) unilaterality of the head pain
without sideshift. Head pain characteristics
include moderate-severe, nonthrobbing, and
nonlancinating pain, usually starting in the neck,
episodes of varying duration, or fluctuating,
continuous pain. Other characteristics of some
importance: only marginal effect or lack of effect
of indomethacin, only marginal effect or lack of
effect of ergotamine and sumatriptan, female
sex, not infrequent occurrence of head, or indirect
neck trauma by history, usually of more
than only medium severity.

Answer 91

A

(D) Neurogenic claudication pain is secondary
to nerve root compression rather than lack of
blood supply that is seen with vascular claudication.
The pain is exacerbated by standing
erect and downhill walking. Improvement
comes with lying supine more than lying in
the prone position, sitting, squatting, and
lumbar flexion. Neurogenic claudication is not
made worse with biking, uphill walking, and
lumbar flexion, unlike vascular claudication.
It is not alleviated with standing.

Answer 92

A

(A) Neck pain has been suggested to have multifactorial
etiologies. Risk factors for neck pain
that cannot be modified include age, sex, and
genetics. There is no evidence that normal cervical
spine degenerative changes are a risk
factor for neck pain. Modifiable risk factors for
neck pain include smoking and exposure to
environmental tobacco. Participation in physical
activity seems to offer a protective effect.
High quantitative job demands, low social support
at the workplace, inactive work position,
repetitive work, and meticulous work increases
the risk of neck pain. There is a lack of evidence
that workplace interventions are successful
in decreasing neck pain in employees.

Answer 93

A

(D) In patients with neck pain, the physical
examination is more predictive at excluding a
structural lesion or neurologic compression
than at diagnosing any specific etiologic condition
in patients with neck pain. Other assessment
tools (ie, electrophysiology, imaging,
injections, discography, functional tests, and
blood tests) lack validity and utility.

Answer 94

A

(B) Most people with neck pain do not experience
a complete resolution of symptoms.
Between 50% and 85% of those who experience
neck pain at some initial point will report neck
pain again 1 to 5 years later. These numbers
appear to be similar in the general population, in
workers, and after motor vehicle crashes. The
prognosis for neck pain also appears to be multifactorial.
Younger age was associated with a
better prognosis, whereas poor health and prior
neck pain episodes were associated with a
poorer prognosis. Poorer prognosis was also
associated with poor psychologic health, worrying,
and becoming angry or frustrated in
response to neck pain. Greater optimism, a
coping style that involved self-assurance, and
having less need to socialize, were all associated
with better prognosis. Specific workplace or
physical job demands were not linked with
recovery from neck pain. Workers who engaged
in general exercise and sporting activities were
more likely to experience improvement in neck
pain. Postinjury psychologic distress and passive
types of coping were prognostic of poorer
recovery in WAD. There is evidence that compensation
and legal factors are also prognostic
for poorer recovery from WAD.

Answer 95

A

(C) The reported complications of fluoroscopically
guided interlaminar cervical epidural
injections are increased neck pain (6.7%), nonpositional
headaches (4.6%), insomnia the night
of the injection (1.7%), vasovagal reaction reactions
(1.7%), facial flushing (1.5%), fever on the
night of the procedure (0.3%), and dural puncture
(0.3%). The incidence of all complications
per injection is 16.8%.

Answer 96

A

(E) Anterior spinal artery syndrome classically
presents in older patients with abrupt motor
loss, sphincter disturbance, and nonconcordant
sensory examination with preservation of sensation
to light touch but loss of pain and temperature.
It may also occur during aortic
procedures. When anterior spinal artery syndromes
occur during or after transforaminal
epidural steroid injection, the patient may have
abrupt back or abdominal pain after injection.
An MRI will demonstrate a T2 signal change
consistent with cord ischemia/infarct. Anterior
spinal artery ischemia may be caused by arteriosclerosis, tumors, thrombosis, hypotension, air or fat embolism, toxins, or other causes. Particulate (steroid) substances, arterial injury, or vascular spasm are other potential causes and have been implicated as significant possibilities for the occurrence of ischemic events after transforaminal
epidural steroid injections.

Answer 97

A

(E) A spinal epidural abscess must be recognized
promptly and treated quickly, otherwise
extreme morbidity can result. It may be separate
or associated with vertebral osteomyelitis.
Diabetic, alcoholic, IV drug using patients, and
immunocompromised patients are all at
increased risk. Staphylococcus aureus is the most
common organism involved. An affected patient
usually presents with neck pain that rapidly
progresses to radicular symptoms. Quadriplegia
can result if left untreated. Treatment involves
surgical removal and antibiotic management.

Answer 98

A

(B) The pathophysiology of HIV-related neuropathies
is still not well understood. The current
understanding is that it is not related to the direct
effect of the virus itself. HIV is not found within
ganglionic neurons of Schwann cells, but only in
endoneurial macrophages, which may generate
a tissue-specific autoimmune response by secretion
of cytokines, which, in turn, promotes trafficking
of activated T cells and macrophages
within the endoneurial parenchyma.

Answer 99

A

(E) The predominantly sensory neuropathy of
AIDS affects up to 30% of people with HIV
infection and AIDS and is the most commonly
encountered.

Answer 100

A

(E) The primary process that leads to vascular
occlusion is the polymerization of sickle cell
hemoglobin on deoxygenation, which in turn
results in distortion of the shape of red blood
cells (RBCs), cellular dehydration, decreased
deformability, and increased stickiness of RBCs,
which promotes their adhesion to and activation
of the vascular endothelium.

Answer 101

A

(D) SCD is unlike other pain syndromes where
the provider can make decisions on treatment
based solely on the pain and its associated
behavior. A primary care physician, for example,
taking care of a middle-aged patient with
job-related low back pain may decide to expel the patient from his or her care if the patient in
question demonstrates suspicious drug-seeking
behavior. Doing the same with patients who
have SCD could be counterproductive. There
are anecdotes of patients with SCD who were
dismissed from certain programs only to be
found dead at home within 24 hours after dismissal
or to be admitted to other hospitals with
serious complications. Sickle cell pain could be
the prodrome of a serious and potentially fatal
complication of SCD in some patients.

Answer 102

A

(C) Tissue ischemia caused by vascular occlusion
resulting from in situ sickling causes
infarctive tissue damage, which in turn initiates
a secondary inflammatory response. The secondary
response may enhance sympathetic
activity by means of interactions with neuroendocrine
pathways and trigger release of
norepinephrine. In the setting of tissue injury,
this release causes more tissue ischemia, creating
a vicious cycle. It is the combination of
ischemic tissue damage and secondary inflammatory
response that makes the pain of SCD
unique in its acuteness and severity.

Answer 103

A

(C) Objective signs of a painful crisis, such as
fever, leukocytosis, joint effusions, and tenderness,
occur in about 50% of patients at initial
presentation.

Answer 104

A

(E) Pain is the hallmark of SCD, and the acute
sickle cell painful episode (painful crisis) is the
most common cause of more than 90% of hospital
admissions among adult patients who
have SCD.

Answer 105

A

(B) NSAIDs have potentially serious, systemic
adverse effects. They include gastropathy,
nephropathy, and hemostatic defects. It is
advisable not to administer them continuously
for more than 5 days to patients with SCD.

Answer 106

A

(D) Tramadol is a synthetic, centrally acting
analgesic that is not chemically related to opioids.
It acts as a weak agonist with preferential affinity
to the μ-receptors. Moreover, it inhibits
neuronal reuptake of both serotonin and norepinephrine
and stimulates the release of serotonin.
Thus, it has functional properties of an opioid and an antidepressant. This drug
received an initial enthusiastic reception based
on the perception that it was not associated with
clinically significant respiratory depression or
addiction potential. However, this enthusiasm
waned after reports indicated that seizures may
be an adverse effect and that abuse potential is increasing.

Answer 107

A

(D) Chronic pain is a major complication of
SCI. Epidemiologic studies indicate that
approximately two-thirds of all SCI patients
suffer from chronic pain out of which one-third
have severe pain. Pain interferes with rehabilitation,
daily activities, quality of life, and may
have significant influence on mood leading to
depression and even suicide.

Answer 108

A

(C) Musculoskeletal pain is common in both
the acute and chronic phase of SCI. Chronic
pain secondary to overuse is common in shoulders
and arm, and vertebral column pain may
occur because of the secondary changes following
fractures and fixation, mechanical instability,
and osteoporosis.

Answer 109

A

(D) Autonomic dysreflexia may complicate SCI
patients with a lesion above the splanchnic outflow
(sixth thoracic level).

Answer 110

A

(E) Visceral pain usually presents as dull or
cramping abdominal uncomfortable and
painful sensations, which may be associated
with nausea and autonomic reactions. It is
likely that visceral pain may occur in the
absence of any abdominal organ dysfunction,
and may in some cases represent a neuropathic
type of pain. SCI patients may not have the
typical signs of abdominal illness, and they
should be carefully examined whenever any
new pain or changes in existing pain occur.
Increases in spasticity, pain at any location, or
autonomic reactions may be the only indications
of abdominal organ dysfunction.

Answer 111

A

(E) Above-level neuropathic pain includes pain
caused by compressive mononeuropathies
(particularly carpal tunnel syndrome) and
CRPS. While below-level pain is considered to
be a central pain caused by the spinal cord trauma, at-level pain may have both peripheral
(nerve root) and central (spinal cord) components
that are difficult to separate.

Answer 112

A

(D) Answers (A), (B), (C), and (D) define allodynia,
aftersensation, hyperalgesia, and referred
pain, respectively.

Answer 113

A

(B) Central cord syndrome is one of the incomplete
SCI syndromes. It is the most common
pattern of injury, representing central gray
matter destruction with preservation of only
the peripheral spinal cord structures, the sacral
spinothalamic and corticospinal tracts. The
patient usually presents as a quadriplegic with
perianal sensation and has an early return of
bowel and bladder control. Any return of
motor function usually begins with the sacral
elements (toe flexors, then the extensors), followed
by the lumbar elements of the ankle,
knee, and hip. Upper extremity functional
return is generally minimal and is limited by
the degree of central gray matter destruction.

Answer 114

A

(D) Sensory symptoms and signs in CRPS
include spontaneous pain, hyperpathia, allodynia,
and hyperalgesia. Answer (A) is the definition
of allodynia, answer (B) defines primary
hyperalgesia, and answer (C) is secondary
hyperalgesia. Answer (E) is the definition of
dysesthesia. Dysesthesia maybe spontaneous.

Answer 115

A

(C) CRPS I is a painful condition following an
injury, which may not even be a neuropathic
pain, as not obvious lesion is present. Patients
with this condition develop asymmetrical distal
extremity pain, which is disproportionate to the
intensity of the initiating event. Sensory abnormalities
appear early in the course of the disease
and are more pronounced distally. No clear relationship
between the injury and the area of pain
distribution exist. Sweating abnormalities,
whether hypohidrosis or hyperhidrosis are
present in nearly all patients with CRPS I.

Answer 116

A

(D) Trophic changes, particularly abnormal
hair growth, fibrosis, decreased dermal blood
flow, thin glossy skin, and osteoporosis are more common in long standing cases, while
the others described present in acute phases of
the disease.

Answer 117

A

(D) The diagnosis of CRPS I and II follows the
IASP clinical criteria. Bone scintigraphy may be
a valuable tool to rule out other conditions.
CRPS I is more common than CRPS II and the
female to male ratio is from 2:1 to 4:1.

Answer 118

A

(D) The symptoms of CRPS II are similar to
those of CRPS I, except that in CRPS II, there
must be a lesion of a peripheral nerve structure
and subsequent focal deficit are mandatory for
the diagnosis.

Answer 119

A

(A) The majority of patients with CRPS present
with significant psychologic distress, being the
most frequent anxiety and depression. Current
evidence is against the theory that CRPS is a
psychogenic condition. The pain in CRPS is the
cause of psychiatric problems and not vice
versa. When compared to patients with low
back pain, CRPS patients showed a higher frequency
of somatization, but other psychologic
parameters were similar.

Answer 120

A

(D) Activation and sensitization of cutaneous C
fibers elicit a response consisting of a wheal
(local edema), a reddening of the skin at the site
of stimulus, and a spreading flare, were the
responses described by Lewis (1927). [Lewis T.
The blood vessels of the human s

Answer 121

A

(A) Muscle pain tends to be dull, poorly localized,
and deep in contrast to the precise location
of cutaneous pain. The diagnosis of
myofascial pain syndrome is confirmed when
the myofascial trigger point is identified by
palpation. An active myofascial trigger point is
defined as a focus of hyperirritability in a
muscle or its fascia that causes the patient pain.
B. Myofascial pain syndrome is usually
thought of as a regional pain syndrome in
contrast to fibromyalgia as a widespread
syndrome; however, as many as 45% of
patients with chronic myofascial pain syndrome
have generalized pain in three or four
quadrants. Hence, regional pain syndromes should raise a suspicion of myofascial pain
syndrome, but patients with widespread
musculoskeletal pain can also have
myofascial pain syndrome.
C. The American Pain Society showed general
agreement with the concept that myofascial
pain syndrome exists as an entity distinct
from fibromyalgia.
D. Systemic palpation differentiates between
myofascial

Answer 122

A

(A) The minimum criteria that must be satisfied
in order to distinguish a myofascial trigger
point from any other tender area in muscle are
a taut band and a tender point in that taut
band. The existence of a local twitch response,
referred pain, or reproduction of the person’s
symptomatic pain increases the certainty and
specificity of the diagnosis.

Answer 123

A

(C)
D. This statement is true. End-plate noise is
characteristic of, but not restricted to, the
region of the myofascial trigger point.
Hence, an objective EMG signature of the
trigger point is now available for diagnostic
and research purposes.

Answer 124

A

(B)
A. There is no reason to believe that the
placebo effect is unusually high with this
or other soothing sprays.
B. The stretch and spray technique combines
the use of a vapocoolant spray with passive
stretching of the muscle. Application of
vapocoolant spray stimulates temperature
and touch A-β skin receptors, thereby inhibiting
C fiber and A-δ fiber afferent nociceptive
pathways and muscle spasms, myofascial
trigger points, and pain when stretching
C. The patient is positioned comfortably and
the muscle involved is sprayed with a
vapocoolant spray, and then the muscle is
stretched passively. With the muscle in the
stretched position, the spray is applied again
over the skin overlying the entire muscle,
starting at the trigger zone and proceeding in the direction of, and including, the
referred pain zone. After, the area is heated
with a moist warm pack for 5 to 10 minutes.
The patient is encouraged to perform full
range of motion exercises with the body
part. This technique can be used in physical
therapy as a separate modality or following
myofascial trigger point injections.
D. It is expected that therapists can be more
liberal once the spray has been applied
owing to less patient discomfort.

Answer 125

A

(C) Myofascial release techniques and sustained
pressure may soften and relax contracted
and hardened muscles. The principle of
the least possible force is applied, instead of
applying high stress to the muscle. Effective
myofascial release techniques include strumming.
Strumming is when a finger runs across
a taut band at the level of the trigger point over
the nodules from one side of the muscle to the
other. The operator’s fingers pull perpendicularly
across the muscle rather than along the
length of the fibers. When the nodule of the
trigger point is encountered, light pressure is
maintained until the operator senses tissue
release. Other techniques include perpendicular
and oscillating mobilizations, tissue rolling,
connective tissue massage, and deep muscle
massage consisting of effleurage (stroking massage
technique) and pétrissage (kneading massage
technique).
After superficially passing over the muscles
and adjacent muscles, massage therapy
can be applied directly to the taut band and
trigger points. Exercise and massage helped to
reduce the number and intensity of trigger
points, but the addition of therapeutic ultrasound
did not improve the outcome.

Answer 126

A

(C) When treating myofascial pain, the physician
must evaluate and, if indicated, treat both soft
tissue and joint dysfunction. Restrictions in joint
capsules hinder the function of the muscles that
overlie the joint, while muscle irregularities result
in joint capsule restrictions. Zygapophyseal joints
may have pain referral patterns that are analogous
to myofascial trigger points. The limited
range of motion and weakness that results from this somatic dysfunction that affects muscles and joints can be reversed easily by manual therapy.

Answer 127

A

(D) Answers A., B., and D. are the therapeutic,
diagnostic, and adjunctive indications for
myofascial trigger point needling, respectively,
with D. being the most common appropriate
use of this technique. Rarely is dry needling
done to eliminate a trigger point permanently,
although, this can happen when the myofascial
pain syndrome is acute.
Inactivation of the myofascial trigger
point appears to be the result of the mechanical
action of the needle in the trigger point
itself, because it also occurs when no medication
is used. However, using local anesthetics
is more comfortable for the patients and
results in longer lasting pain reduction.
After pinpointing and manually stabilizing
the trigger point in the taut band with the fingers,
the needle is quickly passed through the skin and
into the trigger zone. Alocal twitch response or
a report of referred pain indicates that the trigger
zone has been entered. One-tenth to 0.2 mL
of local anesthetic can be injected. The needle
is pulled back to just below the skin, the angle is
changed, and it is once again inserted through
the muscle to another trigger zone. In this way a
funnel-shaped volume of muscle can be evaluated
without withdrawing the needle through the
skin. The trigger zone is explored this way until
no further local twitch responses are obtained. By
this time, the taut band is usually gone and the
spontaneous pain of the trigger point has subsided.
Experienced patients know when trigger
points have been inactivated.

Answer 128

A

(E)
A., B., and C. While direct needling of myofascial
trigger points appears to be an effective
treatment, there is insufficient evidence that
needling therapies have efficacy beyond
placebo. These researchers also found no
evidence to suggest that the injection of one
material was more effective than another.
They found no advantage to adding steroids,
ketorolac, or vitamin B12 to local anesthetic.
Steroids actually have the disadvantage
that they are locally myotoxic and that repeated administration can produce all the
unwanted side effects associated with
steroids. For those who are allergic to local
anesthetics, saline or dry needling can be
used.
D. No studies have been done to confirm or
refute that diphenhydramine increases the
efficacy of myofascial trigger points.

Answer 129

A

(E) Complications of trigger point injections:
• Local bleeding into muscle
• Local swelling
• Painful contraction of a taut band from
inadequate myofascial trigger point inactivation
(missing the trigger point)
• Infection
• Perforation of a viscous body, most commonly
the lung
• Nerve injury from direct trauma by the needle
• Transient nerve block
• Syncope
• Allergic reaction from the anesthetic
Torticollis is a contraction, often spasmodic,
of the muscles of the neck, chiefly those
supplied by the spinal accessory nerve; the
head is drawn to one side and usually rotated
so that the chin points to the other side. While
missing the trigger point during needling can
cause a painful contraction of a taut band, torticollis
has not been noted.

Answer 130

A

(B) Answers (A), (C), (D), and (E) are all causes
of trigger point failure.
C. Myofascial adhesions can possibly develop
with secondary or “satellite” trigger points in
nearby muscles. Trigger points appearing in
muscles that are part of a functional unit
must be treated together. Muscles that work
together as agonists or in opposition as
antagonists, constitute a functional muscle
unit. For example the trapezius and levator
scapula muscles work together as agonists
in elevation of the shoulder, but are antagonists
in rotation of the scapula, the trapezius
rotating the glenoid fossa upward and the
levator scapula rotating it downward.

Answer 131

A

(A) The most common anatomic variations that
constitute mechanical factors precipitating
myofascial pain are: leg length discrepancy and
small hemipelvis, short upper arm syndrome,
and the long second metatarsal syndrome.
The leg length disparity syndrome produces
a pelvic tilt that results in a cascade of
chronic contraction and activation of a chain of
muscles in an attempt to straighten the head
and level the eyes. The quadratus lumborum
and paraspinal muscles contract to correct the
deviation of the spine caused by the pelvic tilt.
Unwarranted loading perpetuates myofascial
trigger points and may result in low back,
head, neck, and shoulder pain. Trigger points
in these persistently shortened and constantly
contracted muscles are not easily inactivated
until the muscles are unloaded. The quadratus
lumborum is less likely to develop trigger
points during the teenage years, and typically,
unilateral low back pain is located on the side
of the shorter leg because of early shrinking of
the ipsilateral annulus fibrosis. In adults, it
occurs on the side of the longer leg, caused by
later spondylitic changes and quadratus lumborum
shortening. A true leg length incongruity
can be corrected by placing a heel lift on
the shorter leg. The asymmetry caused by a
small hemipelvis is corrected by placing an
ischial or “butt” lift under the ischial tuberosity.
Short upper arms cause forward shoulder
roll, pectoral muscle shortening, and abnormal
loading of the neck and trunk muscles as
the individual attempts to find a comfortable
position when seated.
Along second metatarsal bone obscures the
stable tripod support of the foot produced by
the first and second metatarsal bones anteriorly
and the heel posteriorly. In contrast, in this condition,
weight is carried on a knife-edge from
the second metatarsal head to the heel, overstressing
the peroneus longus that attaches to
the first metatarsal bone. Diagnostic callus formation
takes place in the abnormally stressed
areas: under the second metatarsal head, and
on the medial aspect of the foot at the great toe
and first metatarsal head. Correction is accomplished
with support under the head of the first
metatarsal.

Answer 132

A

(E)
A. In women with chronic coldness and
myofascial pain, ferritin has been found to
be below 65%, largely because of an iron
intake that is insufficient to replace menstrual
loss. GI blood loss caused by antiinflammatories
and parasitic diseases can
also cause ferritin to be low. Ferritin represents
the tissue bound nonessential iron stores
in the body that supply the essential iron
for oxygen transport and iron-dependent
enzymes. Fifteen to 20 ng/mL is low and
anemia is common at levels of 10 ng/mL or
less. The association between depleted iron
and chronic myofascial pain hints that ironrequiring
enzymatic reactions may be limited
in these people, which may produce an
energy crisis in muscle when it is overloaded
and thereby produce metabolic stress.
Myofascial trigger points will not easily
resolve in such instances, and iron supplementation
in patients with chronic myofascial
pain syndrome and serum ferritin levels
below 30 mg/mL prevents or corrects these
symptoms.
B. and C. Folic acid and vitamin B12 function
not only in erythropoiesis but also in central
and peripheral nerve formation. Preliminary
studies have shown that 16% of patients
with chronic myofascial pain syndrome
either were deficient in vitamin B12 or had
insufficient levels of vitamin B12, and that
10% had low serum folate levels.
D. Hypothyroidism can be suspected in
chronic myofascial pain syndrome when
coldness, dry skin/hair, constipation, and
fatigue are also present. One study, found
that under these circumstances (chronic) it
occurred in 10% of patients. The myofascial
trigger points tend to be more extensive in
hypothyrotic patients. Hormone replacement
may resolve many myofascial complaints
and perpetuate a more permanent
healthy state by allowing the implementation
of physical therapy and trigger point
inactivation.
Also common in chronic musculoskeletal
pain: low vitamin D, recurrent candida yeast
infections, elevated uric acid levels, parasitic
infections (especially amebiasis), Lyme disease,
osteoarthritis, rheumatoid arthritis, Sjögren
syndrome, carpal tunnel syndrome, and peripheral
neuropathy secondary to DM.
The postlaminectomy syndrome is frequently
caused by myofascial trigger points.

Answer 133

A

(D) Biologic abnormalities that are detected in
most fibromyalgia patients include
• Dysfunctional sleep by polysomnography
• Physiological or biochemical evidence for
central sensitization
• Temporal summation or second pain
• Lowered thresholds to pressure-induced
pain detected by brain imaging
• Low levels of the biogenic amines to drive
descending inhibition of nociception
• Elevated spinal fluid levels of substance P
• In primary fibromyalgia only, elevated
spinal fluid levels of NGF

Answer 134

A

(D) The American College of Rheumatology
sanctioned a study that led to the criteria for
diagnosing fibromyalgia: a history of widespread
pain for at least 3 months and pain sensitivity
to 4 kg of digital pressure at 11 or more
of 18 anatomically defined tender points. The
criteria displayed sensitivity and specificity of
88.4% and 81.1%, respectively, for patients
with fibromyalgia against normal control
and disease control subjects with other painful
conditions.

Answer 135

A

(C) In addition to the four areas mentioned
in the question stem, five other locations
exist:
Trapezius, at the middle of the upper muscle
border
Supraspinatus, near the origins, above the
spine of the scapula
Second rib, upper surface just lateral to the
second costochondral junction
Gluteal, in upper outer quadrants of buttocks
in anterior fold of muscle
Greater trochanter, posterior to the trochanteric
prominence

Answer 136

A

(B)
A. and B. Fibromyalgia is no longer considered
a psychogenic disorder, however,
there is a subgroup of fibromyalgia patients
with associated depression or anxiety.
C. It is believed that fibromyalgia patients
who have had medical treatment are more
apt to exhibit symptoms of depression than
those in the community who have not.
D. Sexual abuse in childhood is no longer
considered a legitimate hypothesis for the
origination of fibromyalgia.

Answer 137

A

(E) The female urethral syndrome or irritable
bladder syndrome constitutes urinary frequency,
dysuria, suprapubic discomfort, and
urethral pain despite sterile urine.

Answer 138

A

(E)
A., B., and C. Most patients (90%) with
fibromyalgia have trouble sleeping. Some
have difficulty getting to sleep (initial insomnia),
while the majority awaken feeling alarmingly
alert after only a few hours of sleep (mid
insomnia) and are then unable to sleep
soundly again until near morning (terminal
insomnia). They usually awaken in the morning
feeling incredibly stiff (lasts 45 minutes
to 4 hours), mentally listless, and unrefreshed
by their sleep. Hence, it is surprising that they
have difficulty napping during the day.
Moldofsky (2002) observed that 60% of
fibromyalgia patients exhibit an electroencephalogram
(EEG) pattern of sleep architecture
called alpha wave intrusions of deep, delta
wave, non–rapid eye movement sleep, which
relates to subjective fatigue and psychologic
distress but is not specific for fibromyalgia. Its
prevalence in the healthy general population
or in those with insomnia or dysthymia is
only 25%. [

Answer 139

A

(E) Approximately 80% of patients with
fibromyalgia have fatigue, while a small percentage
of these actually meet the criteria for
chronic fatigue syndrome (CFS). CFS is thought
to affect approximately 4 per 1000 adults. For
unknown reasons, CFS occurs more often in
women and in adults in their 40s and 50s. The
illness is estimated to be less prevalent in children
and adolescents, but study results vary as
to the degree. CFS often manifests with widespread
myalgia and arthralgia, cognitive difficulties,
chronic mental and physical exhaustion,
often severe, and other characteristic symptoms
in a previously healthy and active person. There
remains no assay or pathologic finding which is
widely accepted to be diagnostic of CFS. It
remains a diagnosis of exclusion based largely
on patient history and symptomatic criteria,
although a number of tests can aid diagnosis.
The fatigue of CFS is a feeling of weakness,
while the fatigue of fibromyalgia is a feeling of
tiredness. Fatigue may result from sedating
medications (ie, TCAs being used for the treatment
of insomnia in fibromyalgia). The rest of
the differential diagnosis is quite extensive and
must take into account:
• Sleep disorders
• Chronic infections
• Autoimmune disorders
• Psychiatric comorbidities
• Neoplasia

Answer 140

A

(B) The rest of the answers are blatantly wrong.
Secondary fibromyalgia may not be clinically distinguishable
from that of primary fibromyalgia.
Examples of secondary fibromyalgia:
• Rheumatoid arthritis patients have fibromyalgia
30% of the time
• Systemic lupus erythematosus (SLE) 40%
• Sjögren syndrome 50%
• Lyme disease 20%; the symptoms of
fibromyalgia may develop 1 to 4 months after
infection, often in association with Lyme
arthritis. The signs of Lyme disease will normally
resolve with antibiotics, but the
fibromyalgia symptoms can persist
• Chronic hepatitis
• Inflammatory bowel disease
• Tuberculosis
• Chronic syphilis
• Bacterial endocarditis
• AIDS
• Hypothyroidism
• Hypopituitarism
• Hemochromatosis
Patients with rheumatic disease and concomitant
fibromyalgia experience joint pain
out of proportion to their synovitis. The practitioner
should treat each of the conditions
separately, because increasing the dosage of
antirheumatic medications in the absence of
active inflammation might have minimal effect
on the pain augmented by the fibromyalgia.

Answer 141

A

(A)
A. There are several neurochemical mediators
of pain that appear to be factors in the
pathogenesis of fibromyalgia:
• Substance P
• NGF (elevated in primary fibromyalgia, but
not secondary)
• Dynorphin A (normal or elevated in
fibromyalgia)
• Glutamate
• Nitric oxide
• Serotonin (decreased in fibromyalgia)
• Noradrenaline (its inactive metabolite is
significantly lowered in fibromyalgia)
Substance P, NGF, dynorphin A, glutamate,
and nitric oxide are considered pronociceptive
because they transmit or intensify afferent
signals, leading to the brain perceiving
increased pain. On the other hand, serotonin,
noradrenaline, the amino terminal peptide
fragment of substance P, and endogenous opioids
are considered to be antinociceptive
because they hinder the transmission of nociceptive
signals.
B. All studies on substance P in fibromyalgia
patients have found significantly higher
average concentrations (two- to threefold)
of substance P than in the CSF of healthy
control subjects. However, the levels in
other bodily fluids like saliva, serum, and
urine, have been normal in fibromyalgia.
C. The increased substance P is not because of
decreased CSF substance P esterase activity,
because the rate of cleavage of labeled substance
P was found to be normal. In primary
fibromyalgia, it is believed that NGF
may be responsible for the elevated CSF
substance P through its effects on central
sensitization and neuroplasticity.
D. Increased CSF substance P is not specific
to fibromyalgia as it is also seen in painful
rheumatic diseases irrespective of whether
they have fibromyalgia. In patients that
were status post–total hip replacement,
elevated substance P prior to the procedure
normalized after the surgery when
the pain was gone. Certain chronic conditions
such as low back pain and diabetic
neuropathy present with lower than normal
CSF substance P levels.

Answer 142

A

481. (E) There is no current cure for fibromyalgia, so
its management is
• Nonspecific
• Multimodal
• Expectant
• Symptomatic
The goals are to
• Decrease pain
• Enhance sleep
• Reinstate physical function
• Maintain social interaction
• Restore emotional balance
• Decrease the excessive use of health care
resources
The best way to achieve these goals is through
a multidisciplinary approach of
• Education
• Exercise
• Physical therapy
• Medications
• Social support

Answer 143

A

(B) The shared decision concept emphasizes
the importance of simultaneous exchange of information until an agreement between the
doctor and patient can be achieved concerning
available diagnostic and treatment approaches.
It improves both patient and physician satisfaction,
is preferred by patients, and sets the
stage for better outcomes.
A. The shared decision concept involves the
physician and the patient.
C. The physician may outline the treatment
options with associated risks and benefits,
while the patient may disclose information
about their culture, fears, expectations,
beliefs, and attitudes.

Answer 144

A

(E)
A. All these techniques have been recommended
for some patients with fibromyalgia.
Progressive muscle relaxation was
developed by Jacobson, who argued that
since muscular tension accompanies anxiety,
one can reduce anxiety by learning how
to relax the muscular tension. Jacobson
trained his patients to voluntarily relax certain
muscles in their body in order to reduce
anxiety symptoms. He also found that the
relaxation procedure is effective against
ulcers, insomnia, and hypertension. Selfhypnosis
is a naturally occurring state of
mind which can be defined as a heightened
state of focused concentration (trance), with
the willingness to follow instructions (suggestibility).
Biofeedback is a form of alternative
medicine that involves measuring a
subject’s quantifiable bodily functions such
as blood pressure, heart rate, skin temperature,
sweat gland activity, and muscle tension,
conveying the information to the
patient in real time. This raises the patient’s
awareness and conscious control of their
unconscious physiological activities. By providing
the user access to physiologic information
about which he or she is generally
unaware, biofeedback allows users to gain
control of physical processes previously
considered an automatic response of the
autonomous nervous system.
B. Cognitive-behavioral therapies have
improved pain scores, pain coping, pain
behavior, depression, and physical functioning
over several months in fibromyalgia
patients. It is suspected that follow-ups with
booster sessions may prolong the effects.
While some think that support groups perpetuate
griping, a resource-oriented selfsupport
group can help a fibromyalgia
patient come to terms with an illness and
provide invaluable patient education.
C. Aerobic exercise is one of the first nonpharmacologic
strategies promoted for patients
with fibromyalgia. Low-impact aerobics of
sufficient intensity to produce cardiovascular
stimulation can decrease pain, enhance
sleep, improve mood, increase energy,
advance cognition, and better a patient’s
overall outlook. Fibromyalgia patients who
exercise deal better with the disease.
However, a fibromyalgia patient can also
experience increased pain if the exercise regimen
is too strenuous or carried out during
an inopportune time in the treatment. These
patients should begin with low-impact exercises
(ie, aqua therapy). Continuing the
patient on the exercise regimen becomes easier
as the patient’s pain decreases.
D. Heat helps fibromyalgia patients with tenderness,
stiffness, and cephalgia. It can also
calm muscles, ease exercising, and accentuate
a sense of well-being. Cold application
also works.
E. Some patients do obtain relief by light
massages that progress to more deep sedative
ones.

Answer 145

A

(E)
A. and D. Dopamine is a neurotransmitter best
known for its role in the pathology of schizophrenia,
Parkinson disease, and addiction.
There is also strong evidence for a role of
dopamine in restless leg syndrome, which is
a common comorbid condition in patients
with fibromyalgia. In addition, dopamine
plays a critical role in pain perception and
natural analgesia. Accordingly, musculoskeletal
pain complaints are common among
patients with Parkinson disease, which is
characterized by drastic reductions in
dopamine owing to neurodegeneration of dopamine-producing neurons, while patients
with schizophrenia, which is thought to
arise, at least partly, from hyperactivity of
dopamine-producing neurons, have been
shown to be relatively insensitive to pain.
Interestingly, patients with restless legs syndrome
have also been demonstrated to have
hyperalgesia to static mechanical stimulation.
Fibromyalgia has been commonly
referred to as a “stress-related disorder”
owing to its frequent onset and worsening of
symptoms in the context of stressful events.
It was therefore proposed that fibromyalgia
may represent a condition characterized by
low levels of central dopamine that likely
results from a combination of genetic factors
and exposure to environmental stressors,
including psychosocial distress, physical
trauma, systemic viral infections, or inflammatory
disorders (eg, rheumatoid arthritis,
systemic lupus erythematosus). This conclusion
was based on three key observations:
(1) fibromyalgia is associated with stress;
(2) chronic exposure to stress results in a disruption
of dopamine-related neurotransmission;
and (3) dopamine plays a critical role in
modulating pain perception and central
analgesia in such areas as the basal ganglia
including the nucleus accumbens, insular
cortex, anterior cingulate cortex, thalamus,
periaqueductal gray, and spinal cord. In
support of the “dopamine hypothesis of
fibromyalgia,” a reduction in dopamine synthesis
has been reported after using positron
emission tomography (PET) and demonstrated
a reduction in dopamine synthesis
among fibromyalgia patients in several
brain regions in which dopamine plays a
role in inhibiting pain perception, including
the mesencephalon, thalamus, insular cortex,
and anterior cingulate cortex. A subsequent
PET study demonstrated that, whereas
healthy individuals release dopamine into
the caudate nucleus and putamen during a
tonic experimental pain stimulus (ie, hypertonic
saline infusion into a muscle bed),
fibromyalgia patients fail to release dopamine
in response to pain and, in some cases, actually
have a reduction in dopamine levels
during painful stimulation. Moreover, a
substantial subset of fibromyalgia patients
respond well in controlled trials to pramipexole,
a dopamine agonist that selectively
stimulates dopamine D2/D3 receptors and
is used to treat both Parkinson disease and
restless legs syndrome.
B. Tryptophan is decreased in the serum and
CSF of fibromyalgia patients. Serotonin is low
in fibromyalgia serum. 5-Hydroxytrytophan,
the intermediary between tryptophan and
serotonin, and 5-hydroxyindole acetic
acid, the by-product of serotonin metabolism,
are both low in the CSF of patients
with fibromyalgia. The excretion in urine of
5-hydroxyindole acetic acid was lower than
normal in patients with fibromyalgia, lower
in females versus males, and lower in females
with fibromyalgia versus females who don’t
have fibromyalgia.
C. The numbers of active tender points in
fibromyalgia patients directly correlated
with the concentration of serotonin in
fibromyalgia sera.

Answer 146

A

(C) Fibromyalgia, a common chronic pain condition
characterized by widespread pain, is
thought to originate largely from altered central
neurotransmission. In this study, a sample of 17
fibromyalgia patients and 17 age- and sexmatched
healthy controls, were compared
using μ-opioid receptor PET. PET scans measure
blood flow in the brain. It was demonstrated
that fibromyalgia patients display
reduced μ-opioid receptor binding potential
within several regions known to play a role in
pain modulation, including the nucleus accumbens,
the amygdala, and the dorsal cingulate.
The reduced availability of the receptors
could result from a reduced number of opioid
receptors, enhanced release of opioids that are
produced naturally by the body, or both.
These findings indicate altered endogenous
opioid analgesic activity in fibromyalgia and
suggest a possible reason for why exogenous
opiates appear to have reduced efficacy in this
population. The reduced availability of the
receptor was associated with greater pain among
people with fibromyalgia.
Answers (A), (B), (D), and (E) have no merit.

Answer 147

A

(C)
A. and B. The sedating tricyclic biogenic amine
reuptake drugs, such as amitriptyline and
cyclobenzaprine, are the most commonly
prescribed medications for fibromyalgia
insomnia. These medications are mostly
used in low doses to improve sleep and to
enhance the effects of analgesics (amitriptyline
10-25 mg at night and cyclobenzaprine
5-10 mg at night). Patients can develop
tachyphylaxis to them, but a 1-month
holiday from the drugs may help restore
effectiveness.
C. SSRIs are so stimulating that they can
interfere with sleep, and should never be
taken at bedtime.
D. Benzodiazepine decrease anxiety and
allow less troubled sleep (alprazolam,
clonazepam). Clonazepam in particular
can help control nocturnal myoclonus
when it is associated with fibromyalgia.
E. Pregabalin is a sedative in addition to an
antinociceptive medication.

Answer 148

A

(B) In osteolytic bone metastases, the most
commonly involved sites are vertebrae, pelvis,
ribs, femur, and skull. Upper and lower extremity
bones, except femur, are not commonly
involved.

Answer 149

A

(A) Multiple sites of metastatic epidural spinal
cord compression occur in 17% to 30% of all
patients. This is particularly common in prostatic
and breast carcinoma and uncommon in
lung cancer.

Answer 150

A

(E) Bisphosphonates decrease resorption of
bone directly, by inhibiting the recruitment and
function of osteoclasts, and indirectly, by stimulating
osteoblasts. In patients with bony
metastases, they are the standard therapy for
hypercalcemia after rehydration, and have the
greatest effect in patients with breast cancer
and multiple myeloma. Bisphosphonates also
have an acute pain-relieving effect, which is
thought to be derived from the reduction of
various pain-producing substances.

Answer 151

A

(E) Both gabapentin, an antiepileptic drug, and
amitriptyline, TCA, are widely used in treating
neuropathic pain, which is often a significant
component of a cancer pain syndrome.
Samarium 153 belongs to the group of
bone-seeking radiopharmaceuticals emitting
medium- to high-energy beta particle radiation.
The most commonly used agent in this group is
Strontium 89 with a documented pain-relieving
effect in patients with bony metastases.
Samarium 153, rhenium 186, and phosphorus
32 are also available for clinical use.

Answer 152

A

(E) Both gabapentin (an antiepileptic drug) and
amitriptyline (a TCA) are widely used in treating
neuropathic pain, which is often a significant
component of a cancer pain syndrome.
Samarium 153 belongs to the group of
bone-seeking radiopharmaceuticals emitting
medium- to high-energy beta particle radiation.
The most commonly used agent in this group is
Strontium 89 with a documented pain-relieving
effect in patients with bony metastases.
Samarium 153, rhenium 186, and phosphorus
32 are also available for clinical use.

Answer 153

A

(B) In clinical practice, most peripheral neuropathies
do not produce chronic pain as
impairment of nerve fibers carrying nociception
should result in decrease pain perception.
In most neuropathies, all components of the
peripheral nervous system are affected, presenting
with variable sensorimotor deficit and
autonomic dysfunction.

Answer 154

A

(B) The most commonly activated areas during
acute processing of pain in humans are S-I, S-II,
anterior cingulated cortex, insular cortex, prefrontal
cortex, thalamus, and cerebellum.

Answer 155

A

(C) Many studies suggest that axonal injury
along the nociceptive fiber in the peripheral nervous system is the main cause of neuropathic
pain. Several conditions where the small
fibers are spared support this concept. The
Charcot-Marie-Tooth disease also known as
hereditary motor and sensory neuropathy
where the demyelination is limited to large
myelinated fibers, do not manifest with pain.
Segmental anhidrosis or Ross syndrome where
only autonomic fibers are affected, is also not
painful. On the other hand, conditions affecting
the small nerve fibers, like diabetic neuropathy
or Fabry disease, a rare lipid-storage disorder,
commonly present with pain.

Answer 156

A

(A) Chronic renal failure is associated with
selective loss of large nerve fibers which is
rarely painful. Common symptoms include
restless leg syndrome, distal numbness, and
paresthesias, with distal weakness usually in
the lower extremities.

Answer 157

A

(E) Cytokines, a heterogeneous group of peptides
activate the immune system and mediate
inflammation. They form a complex bidirectional
system that communicates between the
immune system and the CNS. IL-1 is the most
extensively studied cytokine. Intraplantar as
well as intraperitoneal injections of IL-1 reduce
mechanical and probably thermal nociceptive
threshold, which may be blocked by local
cyclooxygenase inhibitors, supporting the role
of prostaglandins in the process. The communicating
pathway between the peripheral
cytokines and the brain may involve vagal
afferents terminating in the nucleus tractus solitarius
and circumventricular sites that lack a
blood-brain barrier.

Answer 158

A

(A) Blockade of the sympathetic innervation
of the head can be documented by the presence
of Horner syndrome, which is characterized
by myosis, ptosis, and enophthalmus.
Associate findings include conjunctival injection,
nasal congestion, and facial anhidrosis.
Horner syndrome is an expected finding after
blockade of the sympathetic afferents to the
face and can not be considered a complication.

Answer 159

A

(E) Behavioral studies have shown that activation
of NMDA receptors are required for the
development and maintenance of pain-related
behaviors. Calcium channels are the key ion
involved in the release of transmitters. Different
subtypes of calcium channels (L-, N-, and P/Qtypes)
may have a differential role depending
on the nature of the pain state. The N-type voltagedependent
calcium channels appear to be the
predominant isoform involved in the pre- and
postsynaptic processing of sensory nociceptive
inputs. Animal and clinical studies have shown
partial pain relief with the use of a specific
N-type calcium channel blocker synthetically
derived from a conotoxin, SNX-111. The generic
name of this substance derived from the snail’s
natural conotoxin is Ziconotide.

Answer 160

A

(A) The effectiveness of opioid agonists in the
management of neuropathic pain has created
significant controversy over the last two
decades. Recent studies have increased our
understanding about this topic. In patients
with SCI and stroke, IV morphine showed poor
effects in reducing spontaneous pain, but significantly
reduced stroking allodynia. Other
studies used alfentanil in the treatment of neuropathic
pain independently of the etiology
and observed decrease in dynamic, stroking
allodynia, and spontaneous pain, while increase
the temperature at which heat pain was detected
and decrease the temperature at which cold
pain was detected.

Answer 161

A

(A) Action potentials in the dorsal horn neurons
are mediated by glutaminergic excitatory
postsynaptic potentials, this activity may be
inhibited predominantly by the inhibition produced
by GABA and/or glycine which causes
fast inhibition of postsynaptic potentials.
GABAAand glycine receptors are ligand-gated
Cl− channels, while GABAB, adenosine, and
opioids exert their typically produced postsynaptic
hyperpolarization by activation of K+
channels.

Answer 162

A

(C) More intense or sustained noxious peripheral
stimulation induce primary afferent nociceptors
to discharge at higher frequencies and
to release from central nociceptor terminals
neuromodulator peptides like CGRP, substance
P, and glutamate. As more and more dorsal horn neurons get depolarized, NMDA receptors
open by removing the Mg2+ blockade,
allowing for intracellular calcium levels to
increase. The end result of these intracellular
signaling cascades is windup.

Answer 163

A

(B) Histopathological studies in patients with
PHN have found ganglion cell loss and fibrosis
and atrophy of the dorsal horn, DRG, dorsal
root, and peripheral nerves. Up to 30% of
patients with PHN have no loss of sensation in
the affected dermatome demonstrating minimal
or no loss of neuronal function and interestingly
thermal sensory thresholds are not
affected or even decreased. Antiviral drugs
have shown disappointing results in patients
with chronic PHN. Heat hyperalgesia is more
common than cold hyperalgesia, which only
occurs in less than 10% of the patients.

Answer 164

A

(B) Phantom pain is equally frequent in men
and women and is not influenced by age in
adults, side or level of amputation, and cause
(civilian versus traumatic) of amputation.
Phantom pain is less frequent in young children
and congenital amputees.

Answer 165

A

(A) Phantom pain is usually intermittent. Only
a few patients are in constant pain. Episodes of
pain are most often reported to occur daily, or
at daily or weekly intervals.
Phantom pain is usually localized to the
distal parts of the missing limb. Pain is normally
felt in the fingers and palm of the hand
in upper limb amputees and toes, foot, or
ankle in lower limb amputees. This may be
because of the larger cortical representation of
the hand and foot as opposed to the lesser representation
of the more proximal parts of the
limb.
The character of phantom pain is usually
described as shooting, pricking, burning, stabbing,
pins and needles, tingling, throbbing,
cramping, and crushing

Answer 166

A

(D) Phantom sensations are more common than
phantom pain, and are experienced by nearly all
amputees. The incidence of phantom sensations
ranges from 71% to 90%, 8 days to 2 years after
amputation. Duration and frequency, but not
incidence, decrease as time passes. Phantom sensations
are less common in congenital amputees
and in patients who underwent amputation
before the age of 6 years
Nonpainful sensations normally appear
within the first days after amputation. The
amputee often wakes up from anesthesia with
a feeling that the amputated limb is still there.
Just after the amputation, the phantom limb
often resembles the preamputation limb in
shape, length, and volume. As time passes, the
phantom fades, leaving back the distal parts of
the limb. For example, upper limb amputees
may feel hand and fingers, and lower limb
amputees may feel foot and toes.
Commonly, upper limb amputees feel the
fingers clenched in a fist, while the phantom
limb of lower limb amputees is often described
as toes flexed In some cases, phantom sensations
include feeling of movement and posture;
however, in others only suggestions of the
phantom are felt.
Telescoping (shrinkage of the phantom) is
reported to occur in about one-third of patients.
The phantom progressively approaches the
stump and eventually becomes attached to it. It
has even been experienced within the residual
limb. Phantom pain does not retard shrinkage
of the phantom.

Answer 167

A

(B) Changes occur in the DRG cells, after a complete
nerve cut. Cells in the DRG show similar
abnormal spontaneous activity and increased
sensitivity to mechanical and neurochemical
stimulation. Local anesthesia of neuromas abolished
tap-induced afferent discharges and tapinduced
accentuation of phantom pain, but
spontaneous pain and recorded spontaneous
activity were unchanged which is consistent
with the activity in DRG cells. DRG cells exhibit
major changes in the expression of sodium channels,
with an altered expression pattern of different
channels.
The sympathetic nervous system may
play a role in generating and especially in
maintaining phantom pain. It was noted that
application of noradrenaline or activation of
the postganglionic sympathetic fibers excites
and sensitizes damaged, but not normal nerve
fibers. Injecting noradrenaline into the skin can reestablish neuropathic pain that has just
been relieved with a sympathetic block and
injecting into a neuroma is reported to be
intensely painful.
The catecholamine sensitivity may also
manifest itself in the skin with a colder limb on
the amputated side, and it has been implied
that phantom pain intensity is inversely related
to the skin temperature of the stump.

Answer 168

A

(A)
Numerous studies on preemptive analgesia
using epidural, epidural/perineural,
and just perineural administration have
been conducted. Only two were noted to
utilize proper patient randomization and
blinding.
Persistent pain has been reported in up to
80% of patients after limb amputation. The
mechanisms are not fully understood, but
nerve injury during amputation is important,
with evidence for the crucial involvement
of the spinal NMDA receptor in central
changes. The study objective was to assess
the effect of preemptively modulating sensory
input with epidural ketamine (an
NMDA antagonist) on postamputation
pain and sensory processing.
The aim of preemptive analgesia is to avoid
spinal sensitization by blocking, in advance,
the cascade of intra-neuronal responses that
take place after peripheral nerve injury.
True preemptive treatment is not likely possible
in patients scheduled for amputation
as most have been suffering from ischemic
pain and are almost certainly presenting
with preexisting neuronal hyperexcitability.
To conclude: epidural blockade has been
shown to be effective in the treatment of
preoperative ischemic pain and postoperative
stump pain.

Answer 169

A

(A) Acidic foods, such as orange juice, carbonated
drinks, tomatoes, and vinegar may aggravate
the symptoms of interstitial cystitis. Spicy
food, alcohol, coffee, chocolate, tea, cola, and
smoking should also be either restricted or
completely eliminated.

Answer 170

A

(C) Sodium pentosan polysulfate (Elmiron) is
an oral analogue of heparin. Inside the bladder,
it acts as a synthetic glycosaminoglycan layer
and fortifies bladder wall defenses from bacteria
by increasing the antiadherent surface of
the bladder mucosa.

Answer 171

A

(E) Endogenous opioid peptides as other neurotransmitters,
such as serotonin, norepinephrine,
and GABA, are thought to be involved in
descending inhibition.

Answer 172

A

(E) Anxiety, fear, helplessness, and sleep deprivation
are part of the vicious cycle of pain.
Cultural background has been shown to play a
significant role in the individual’s pain response.

Answer 173

A

(A) There is evidence that pain-related impairment
of intestinal motility may be relieved by
epidural local anesthetics.

Answer 174

A

(B) Pain in the area of sensory loss, also called
deafferentation pain, or anesthesia dolorosa, is
a prominent sign of a neuropathic pain.
Neuropathic pain generally responds less well
to opioid treatment than somatic pain. One of
the significant signs of neuropathic pain is also
allodynia-a painful response to nonpainful
stimuli. Tapping of neuromas produces radiating
electric shock sensation in the distribution
of the damaged nerve is called Tinel sign—
another feature of a neuropathic pain.

Answer 175

A

(E) Post–burn injury pain has two components:
a constant background pain and an intermittent
procedure-related pain. Continuous infusion of
opioids is useful for control of the background
component of pain. Pain related to wound care,
dressing changes, and others (procedure-related
pain) may require brief but profound analgesia.
This may be achieved by administration of
supplemental IV opioids, or addition of the
adjuvant drugs, such as IV ketamine, IV benzodiazepines,
inhaled nitrous oxide-oxygen mixture,
or even general anesthesia.

Answer 176

A

(E) All answers are correct. Aconcomitant head
injury may be associated with increased intracranial
pressure, which could be considered a contraindication
for an epidural catheter placement.6yt

Answer 177

A

(B) Two types of pain may be found in PHN:
a steady burning or aching, the other, a paroxysmal,
lancinating pain. Both may occur spontaneously
and are usually aggravated by any
contact with the involved skin.

Answer 178

A

(E) All of the listed groups of medication were
found to be effective to some extent in the treatment
of PHN. Amultimodal approach seems to
be more effective because of the synergistic
effect different modes of action

Answer 179

A

(A) Oral steroids may provide pain relief in
acute phase of herpes zoster, as well as shorten
the time to full crusting of lesions. However,
controlled trials showed no benefit in the prevention
of PHN. With the development of
antiviral agents, the use of oral steroids is currently
not recommended because of more frequent
side effects

Answer 180

A

(B) Diabetic amyotrophy is a condition occurring
in diabetic patients, more commonly with
type-2 diabetes, which begins with pain in the
thighs, hips, and buttocks. Weakness and atrophy
of the proximal pelvic muscles groups,
iliopsoas, obturator, and adductor muscles follows
the painful manifestations. It usually does
not involve sciatic nerve, or distal muscles of
the lower extremity. The therapy for diabetic
amyotrophy is primarily supportive.

Answer 181

A

(A) Neuropathic arthropathy (Charcot joint) develops
most often in weight-bearing joints. The predominant
cause is DM, but also associated with
neuropathic arthropathy are leprosy, yaws, congenital
insensitivity to pain, spina bifida,
myelomeningocele, syringomyelia, acrodystrophic
neuropathy, amyloid neuropathy, peripheral
neuropathy secondary to alcoholism and
avitaminosis, SCI, peripheral nerve injury, postrenal transplant arthropathy, intraarticular
steroid injections, and syphilis. The etiology of
Charcot joint is believed to be related to the
destruction of afferent proprioceptive fibers and
subsequent unrecognized trauma to the joint.

Answer 182

A

(D) Across-sectional, community-based survey
of 255 patients with DPNP recruited through
the offices of endocrinologists, neurologists,
anesthesiologists, and primary care physicians
found that NSAIDs were the most commonly
used medications, with 46.7% reporting their
use. This is despite the fact, that there is little
evidence to support the efficacy of NSAIDs in
DPNP, and that NSAIDs have a high potential
for renal impairment in patients with diabetic
neuropathy.

Answer 183

A

(A) Given the frequency of imperfect glycemic
control, attempts have been made to identify
oral medications which can target downstream
metabolic consequences of hyperglycemia,
thereby preventing production of reactive
oxygen species, which are felt to contribute to
diabetic neuropathy. Unfortunately, trials of
aldose reductase inhibitors, which decrease
aberrant metabolic flux, have been disappointing
(eg, sorbinil, zopolrestat).

Answer 184

A

(B) The combination of trigeminal neuralgia
and hemifacial spasm is known as convulsive
tic. It is reported to be more severe in women
than in men. Occasionally, strong spasms
involve all of the facial muscles unilaterally
almost continuously. Seldom, facial weakness
may be present. Convulsive tic may indicate
the presence of a tumor, vascular malformation,
or ecstatic dilation of the basilar artery,
compressing the trigeminal or facial nerves.

Answer 185

A

(A) The diagnostic criteria for trigeminal neuralgia
are: shooting, electric-like, sharp, severe
pain which last for seconds but sometimes
experienced together with pain-free intervals.
The pain is periodic with weeks or months
without pain. The pain is typically unilateral
and triggered by light touch, eating, talking,
or washing.

Answer 186

A

(D) Rarely, trigeminal neuralgia is the presenting
symptom of multiple sclerosis. More often,
trigeminal neuralgia presents in patients with
advanced stages of multiple sclerosis.

Answer 187

A

(C) Glycerol is a nonselective neurolytic agent.
Although less common than with radiofrequency
thermocoagulation, the frequency of
patients affected by sensory loss is high.
Recurrence rate is the highest among all ablative
techniques.

Answer 188

A

(E) The trigeminal neuralgia is the most
common cranial neuralgia and its most frequent
form is idiopathic. The incidence of
trigeminal neuralgia is 5.7 per 1000 females
and 2.5 per 1000 in males. Patients with multiple
sclerosis have a higher risk for trigeminal
neuralgia. Other potential relation was found
in patients with family history.

Answer 189

A

(A) The trigeminal neuralgia is a primary axonal
degenerative disease. The ignition hypothesis
combines the current knowledge of the role of
ion channels in the development of neuropathic
pain. Focal demyelination adjacent to the area of
arterial compression has been shown by electron
microscopy in patients undergoing posterior
fossa surgery. In up to 30% of patients with arterial
cross compression, there is a groove or an
area of discoloration lateral where the root entry
zone would be expected.

Answer 190

A

(C) SIH and PDPH have similar presentation,
pathophysiology, and treatment. The most
important distinction is the initiating event,
which is obvious in PDPH. MRI of the brain
with gadolinium enhancement in patients with
SIH shows meningeal enhancement, and thickening,
and a possible caudad shift of the brain
toward the foramen magnum. The most common
location of spontaneous dural tear is the thoracic
region followed by the cervicothoracic
and thoracolumbar junction regions.

Answer 191

A

(B) It has been shown that keeping a supine
position for 2 hours after the EBP provides
higher chances of success when compared with
30 minutes. Although initial relief is very high
(close to 100%), the overall long-term relief of PDPH after EBP is between 61% and 75%. The
effectiveness of EBP is reduced when the dural
tear was caused by a large-size needle.

Answer 192

A

(C) Two important factors in the prevention of
PDPH are the use of small and blunt bevel
spinal needles. Other factors that may prevent
the development of PDPH include the use of
paramedian approach (with angles of 35° or
greater) and the use of intrathecal catheters. Bed
rest as a preventive measure is not effective.

Answer 193

A

(E) Cervicogenic headache is defined as
headache that arises from painful disorders of
structures in the upper neck, which generates
irritation of the upper cervical roots or their
nerve branches. The current classification by
the IHS and the IASP accepts these headaches
to be unilateral or bilateral. All the other
options in the questions are true.

Answer 194

A

(E) According to the International Headache
Society and the IASP, cervicogenic headache
(CGH) is a pain originated in the neck, mostly
unilateral although it may be bilateral, exacerbated
by neck movement, and alleviated by
local anesthetic block of the occipital nerve.
The prevalence of CGH is 0.4% to 2.5% in the
general population and may account for up to
15% to 20% of patients with chronic headache,
more common in females with a 4:1 ratio and
mean age of patients with 42.9 years.

Answer 195

A

(A) During the aura in classic migraine a
decrease in cerebral blood flow decreases
spreads from the occipital cortex. The variation
in the cerebral blood flow causes the aura
and activates trigeminal nerve endings. It is
possible that cortical spreading depression may
stimulate peripheral nerve terminals of the
nucleus caudalis trigeminalis.

Answer 196

A

(B) During the aura in classic migraine there is
a decrease in cerebral blood flow.
In patients with classic migraine (migraine
with aura), there is increase of cerebral blood
flow that happens after the headache begins
and this change persist until the headache
resolves. In migraine without aura, there is no
change in cerebral blood flow.

Answer 197

A

(E) Migraine is a risk factor for affective disorders.
When comparing with nonmigraineurs,
patients with migraine have a 4.5-fold increased
risk of major depression, a sixfold risk of manic
episodes, a threefold increase in anxiety disorder,
and a sixfold prevalence in panic disorder.

Answer 198

A

(A) Although migraine begins in the first three
decades of life, the higher prevalence is in the
fifth one. Family history is a common finding,
and pregnant females often experience worsening
symptoms in the first trimester and
improvement during the third. Many women
experience improvement of their symptoms
after natural, but not surgical menopause.

Answer 199

A

(C) Muscle tenderness is common in patients
suffering from TTH, but is not secondary to
pericranial muscle contraction or ischemic pain
in response to emotion or stress. Increased
EMG activity is independent of tenderness and
pain. Reduced pain threshold observed in
chronic TTH may be the result of low CNS
levels of serotonin. Although TTH can begin at
any age, the most common onset is during adolescence
and young adulthood. The prevalence
of TTH decreases with increasing age.

Answer 200

A

(E) For any structure to be considered as a
source for low back pain it must have the following
characteristics: a nerve supply, the capability
of causing low back pain similar to what
is seen clinically (ideally in healthy volunteers),
a susceptibility to disease or injuries known to
be painful, and should be able to be shown as
a source of pain using diagnostic techniques
of known reliability and validity

Answer 201

A

(A) There have been RCTs showing that lumbar
supports and back schools are not effective in
preventing back pain. Exercise has been proven
by RCTs to prevent back pain. To date, there are
no RCTs on the effectiveness of ergonomics in
preventing back pain.

Answer 202

A

(E) The most significant anomalies of the
lumbar nerve roots are aberrant courses and
anastomoses between nerve roots. Type 1
anomalies are aberrant courses of which there
are two kinds. Type 1A describes two pairs of nerve roots arising from a single dural sleeve,
whereas type 1B defines a dural sleeve arising
from a low position on the dural sac. Type 2
anomalies include those in which the number
of roots in the intervertebral foramen varies.
An empty foramen is classified as type 2A, and
a foramen with extra nerve roots is known as a
type 2B. Type 3 anomalies are those involving
extradural anastomoses between roots in which
a bundle of nerves leaves on dural sleeve to
enter one nearby. Type 3 anomalies may coexist
with type 2 anomalies.

Answer 203

A

(E) The IASP published standardized terms to
define low back pain as pain perceived to arise
for lumbar spinal pain and/or sacral spinal
pain. Lumbar spinal pain is defined as pain
perceived to arise from the region bordered
superiorly by an imaginary line through the
T12 spinous process, inferiorly by a line
through the S1 spinous process, and laterally
by the lateral borders of the erector spinae.
Sacral spinal pain is that defined as pain perceived
to arise from the region bordered laterally
by imaginary vertical lines through the
posterior superior and posterior inferior iliac
spines, superiorly by a transverse line through
the S1 spinous process, and inferiorly by a
transverse line through the posterior sacrococcygeal
joints.

Answer 204

A

(E) Transforaminal injections have been the cause
of some of the most worrisome recent complications.
These included cerebellar and cerebral
infarct, SCI, and infarction, massive cerebral
edema, paraplegia, visual defects with occlusion
following particulate depo-corticosteroids, anterior
spinal artery syndrome, persistent neurologic
deficits, transient quadriplegia, cauda
equina syndrome, subdural hematoma, and
paraplegia following intracordal injection during
attempted epidural anesthesia under general
anesthesia.

Answer 205

A

(C) Despite its controversial history, disc stimulation
(formerly known as discography)
remains the only means by which to determine
whether or not a disc is painful. The test is positive
if upon stimulating a disc the patient’s
pain is reproduced provided that stimulation of adjacent discs does not reproduce their pain.
Discs are also considered to be symptomatic
only if pain is reproduced at injection pressures
less than 50 psi and preferably less than 15 psi.
At injection pressures greater than 80 psi, some
discs are painful in normal individuals. The
stimulation of discs has been complemented
by another approach, heating a wire electrode
that has been inserted into a disc annulus.
Heating a disc evokes pain that is perceived in
the back. This pain may also radiate to the
lower extremities and be responsible for
referred pain in the thigh and leg.

Answer 206

A

(B) Chemonucleolysis is indicated for contained
disc protrusions causing sciatic pain that
have been unresponsive to conservative management.
The injection is contraindicated for
extruded and sequestered disc herniations, and
in patients with cauda equine syndrome.
Relative contraindications include previous
chymopapain injections, previous surgery for
lumbar disc herniation, spinal stenosis, severe
degenerative disc or facet osteoarthritis, and
spondylolisthesis.

Answer 207

A

(E) Inappropriate or premature selection of
patients for surgery is the most common cause
of FBSS. The second most common cause is
persistence of pain secondary to irreversible
neural injury. A less common cause is inadequate
surgery. Lastly, a variant of FBSS results
from new pathologic processes initiated by the
initial surgery.

Answer 208

A

(A) The American Association of Neurological
Surgeons and the American Academy of
Orthopedic Surgeons have published criteria
for patient selection for elective lumbosacral
spine surgery. They are applicable to new
patients, as well as FBSS patients. They include
the following:
Failure of conservative therapy.
An abnormal diagnostic imaging study showing
nerve root or cauda equina compression
and/or signs of segmental instability consistent
with the patient’s signs/symptoms.
Radicular pain with one or more of the
following: (a) corresponding dermatomal segmental sensory loss, (b) corresponding
dermatomal motor loss, (c) abnormal deep
tendon reflexes consistent with appropriate
dermatomes.

Answer 209

A

(A) There are three main types of cervical
spine involvement in rheumatoid arthritis:
atlantoaxial subluxation, cranial settling, and
subaxial subluxation. The inflammatory
changes affecting synovial joints and bursae
target structures lined with a synovial membrane
in the cervical spine. Patients with cervical
spine involvement are thought to have a
more severe form of rheumatoid arthritis, and
their prognosis is usually worse. Occipital
condylar fractures result from a full-energy
blunt trauma complemented with axial compression,
lateral bending, or rotational injury
to the alar ligament.

Answer 210

A

(E) The Québec Task Force (QTF) was a task
force sponsored by the Société de l’assurance
automobile du Québec, the public auto
insurer in Quebec, Canada. In 1995, the QTF
submitted a report on WADs which made
specific recommendations on prevention, diagnosis,
and treatment of WAD. These recommendations
have become the base for Guideline on
the Management of Claims Involving Whiplash-
Associated, a guide to classifying WAD and
guidelines on managing the disorder. The full
report titled Redefining “Whiplash” was published
in the April 15, 1995 issue of Spine. An
update was published in January 2001.
Four grades of WAD were defined by the
QTF :
Grade 1: Complaints of neck pain, stiffness or
tenderness only but no physical signs are
noted by the examining physician.
Grade 2: Neck complaints and the examining
physician finds decreased range of motion
and point tenderness in the neck.
Grade 3: Decreased range of motion plus neurologic
signs, such as decreased deep tendon
reflexes, weakness, insomnia, and sensory
deficits.
Grade 4: Neck complaints and fracture or dislocation,
or injury to the spinal cord.

Answer 211

A

(A) The distraction test is performed with an
examiner standing behind a seated patient, lifting
their head from the chin and occiput, and
removing the weight of the head from the neck.
If relief of neck pain occurs, the test might point
to foraminal intrusion on a nerve root as the
source of pain.

Answer 212

A

(A) Spurling maneuver is used to identify
nerve root compression or irritation. The head
is tilted toward the affected side and manual
pressure is applied to the top of the head.
Radicular pain should be reproduced with
this maneuver. Valsalva test allows a patient to
experience painful or sensory changes when
bearing down. The test increases intrathecal
pressure and exacerbates compression within
the cervical canal caused by tumors, infections,
disc herniations, or osteophyte changes.
The distraction test is performed with an
examiner standing behind a seated patient,
lifting their head from the chin and occiput,
and removing the weight of the head from the
neck. If relief of neck pain occurs, the test
might point to foraminal intrusion on a nerve
root as the source of pain. Adson test is used
to assess vascular compromise because of subclavian
artery impingement from thoracic
outlet syndrome.

Answer 213

A

(D) Peripheral neuropathic pain syndromes in
patients with HIV infection tend to be specific
to the stage of HIV infection as outlined in
answers (1) through (3).

Answer 214

A

(A) In patients with predominantly sensory
neuropathy of AIDS, the complaints are
mostly sensory. However, the NCV and EMG
studies demonstrate both sensory and motor
involvement.

Answer 215

A

(E) Psychostimulants, such as dextroamphetamine,
methylphenidate, may be useful agents
in patients with HIV infection or AIDS who
are cognitively impaired. Psychostimulants
enhance the analgesic effects of the opioid
drugs. They are also useful in diminishing
sedation secondary to opioids. In addition, psychostimulants
improve appetite, promote sense of well-being, and improve feelings of weakness
and fatigue in patients with malignancies.

Answer 216

A

(B) Tissue injury generates several major pain
mediators, including, but not limited to IL-1,
bradykinin, K+, H+, histamine, substance P, and
CGRP. The pathway for painful stimuli is subject
not only to activators, sensitizers, and facilitators
but also to inhibitors. Serotonin,
enkephalin, β-endorphin, and dynorphin are
endogenous central pain inhibitors.

Answer 217

A

(E) SCD is a quadrumvirate of: (1) pain syndromes,
(2) anemia and its sequelae, (3) organ
failure, including infection, and (4) comorbid
conditions. Pain, however, is the insignia of
SCD and dominates its clinical picture throughout
the life of the patients. Pain may precipitate
or be itself precipitated by the other three components
of the quadrumvirate.

Answer 218

A

(C) Avascular necrosis is the most commonly
observed complication of SCD in adults.
Although it tends to be most severe and disabling
in the hip area, it is a generalized bone
disorder in that the femoral and humeral heads
and the vertebral bodies may be equally
affected. Treatment of avascular necrosis is
symptomatic and includes providing nonopioid
or opioid analgesics in the early stages of
the illness; advanced forms of the disease
require total joint replacement. Core decompression
appears to be effective in the management
of avascular necrosis if performed
during its early stages

Answer 219

A

(B) Leg ulceration is a painful and sometimes
disabling complication of sickle cell anemia
that occurs in 5% to 10% of adult patients with
SCD. With good localized treatment, many
ulcers heal within a few months. Leg ulcers
that persist beyond 6 months may require skin
grafting, although results of this treatment have
been disappointing. Recent advances in management
include the use of platelet-derived
growth factor, prepared either autologously
(Procuren) or by recombinant technology
(Regranex).

Answer 220

A

.570. (A) Sickle cell anemia affects millions throughout
the world. It is particularly common among
people whose ancestors come from sub-
Saharan Africa; Spanish-speaking regions
(South America, Cuba, Central America); Saudi
Arabia; India; and Mediterranean countries
such as Turkey, Greece, and Italy

Answer 221

A

.571. (E) General management of vasoocclusive crisis
during pregnancy begins with aggressive
hydration to increase intravascular volume and
decrease blood viscosity. Supplemental oxygen
is essential in those patients with hypoxemia.
Partial exchange transfusions are used to reduce
polymerized hemoglobin S. Prophylactic transfusions
may reduce the incidence of severe sickling
complications during pregnancy.

Answer 222

A

(E) Some patients with SCD are opioid-tolerant
secondary to their home opioid management.
Therefore, the home opioid requirement should
be taken into account for faster and more efficient
pain control of sickle crisis pain. Opioid
titration, however, may require some additional
care because hypoxemia and hypercarbia
further exacerbate sickling of erythrocytes.

Answer 223

A

(D) Autonomic dysreflexia is a potential lifethreatening
condition, which is triggered by
sensory input below the lesion and manifests
itself with increased blood pressure, headache,
and a risk of cerebral hemorrhage and seizure.

Answer 224

A

(C) Anterior cord syndrome is a common
incomplete cord syndrome. A patient with
anterior cord syndrome may exhibit complete
motor and incomplete sensory loss, with the
exception of retained trunk and lower extremity
deep pressure sensation and proprioception.
This syndrome carries the worst prognosis
for return of function, and only a 10% chance of
functional motor recovery has been reported.

Answer 225

A

(B) Posterior cord syndrome is a rare incomplete
cord syndrome consisting of loss of the
sensations of deep pressure and deep pain and
proprioception, with otherwise normal cord
function. The patient ambulates with a footslapping
gait similar to that of someone
afflicted with tabes dorsalis.

Answer 226

A

(E) Brown-Séquard syndrome is an uncommon
incomplete spinal cord syndrome. It is anatomically
a unilateral cord injury, such as a missile
injury. It is clinically characterized by a motor
deficit ipsilateral to the SCI in combination
with contralateral pain and temperature hypesthesia.
Almost all these patients show partial
recovery, and most regain bowel and bladder
function and the ability to ambulate.

Answer 227

A

(A) Anticonvulsants have several pharmacologic
actions, such as modulation of sodium
and calcium channels, increasing GABA inhibition,
and suppressing abnormal neuronal
hyperexcitability, which suggest an effect in
neuropathic pain

Answer 228

A

(E) Patient with autonomic dysreflexia usually
exhibit decline in heart rate, dramatic changes
in blood pressure, flushing and sweating above
the level of the injury, and a marked reduction
on peripheral blood flow through the reflex
pathways in the preserved vagus nerves.

Answer 229

A

(C) HO is the formation of mature, lamellar
bone in nonskeletal tissue, usually occurring
in soft tissue surrounding joints. The bone formation
in HO differs from other disorders of
calcium deposition in that HO results in encapsulated
bone between muscle planes, not intraarticular
or connected to periosteum.
In neurogenic HO secondary to TBI or
SCI, the hip is the most common joint affected.
Even though the most common symptom
of HO is pain, it may be painless in patients
with complete SCI.
Etidronate disodium, a bisphosphonate, is
an osteoclast inhibitor. It is structurally similar
to inorganic pyrophosphate and is shown
to delay the aggregation of apatite crystals
into large, calcified clusters in patients with
TBI and SCI. The recommended prophylactic
treatment for HO in SCI is 20 mg/kg/d for
2 weeks, then 10 mg/kg/d for 10 weeks. The
current treatment recommendation for established
HO is 300 mg IV daily for 3 days followed
by 20 mg/kg/d for 6 months in spinal
cord patients.

Answer 230

A

(E) Localized neurogenic inflammation may
explain the acute edema, vasodilation, and
sweating observed in early stages of CRPS.
Increased protein concentration and synovial
hypervascularization is observed in the intraarticular
fluid of affected joints. Findings that
support the role of neurogenic inflammation
in the generation of CRPS include elevated systemic
levels of CGRP and local increase of
IL-6 and tumor necrosis factor alpha in artificially
produced blisters.

Answer 231

A

(C) Up to 50% of CRPS patients show decrease
range of motion, increase amplitude of physiologic
tremor, and reduce active motor force,
with dystonia of the affected limb observed in
only 10% of the chronic cases. Those motor
changes are unlikely associated with a peripheral
process and more likely the result of
changes of activity in the motor neurons which
point to abnormalities of cerebral motor processing.

Answer 232

A

(C) It is estimated that the risk of CRPS after
fractures is 1% to 2% and 12% after brain
lesions. Retrospective studies in large cohorts
shows a distribution in the upper and lower
extremity from 1:1 to 2:1. CRPS following SCI
are rare. Affected extremities after brain injury
are more likely affected than unaffected ones.

Answer 233

A

(E) The three stages of the three-phase bone scan
include the perfusion phase 30 seconds postinjection,
the blood-pool is 2 minutes postinjection,
and mineralization phases is evaluated
3 hours postinjection. Homogeneous unilateral
hyperperfusion in the perfusion and blood-pool
phase is consistent with CRPS and excludes the
differential diagnosis of osteoporosis because of
inactivity. The mineralization phase in patients
with CRPS shows elevated unilateral periarticular
uptake.

Answer 234

A

(A) The major peripheral pathologic findings in
CRPS patients include (a) patchy atrophy of
some muscle cells, secondary to disuse and
nerve damage; (b) capillary microangiopathy,
with accelerated turnover of endothelial cells and pericytes; (c) Wallerian degeneration of
several types of axons; and (d) focal osteopenia
in the territory innervated by a damaged nerve,
and synovial cell disorganization and edema.

Answer 235

A

(B) Medical procedures are the second most
common cause of CRPS. The finding of exaggerated
deep tendon reflexes in CRPS patients
has been attributed to cortical disinhibition.
Focal deficit of touch (hypoesthesia) were present
in 50% of patients. Brushing skin activates
low threshold mechanoreceptors which under
normal circumstances has no connections with
central pain neurons. Brush evoked pain (cutaneous
dynamic mechanical allodynia)is a hallmark
of central sensitization.

Answer 236

A

(A) In contrast to CRPS II which has similar
frequencies in boys and girls, CRPS I is more
common in girls with a ratio of 4:1. The lower
extremity is more affected (5:1 ratio). CRPS I is
more common in Caucasians. There is also evidence
that CRPS may have a genetic predisposition,
with increase incidence in patients with
HLAA3, B7, and DR2.

Answer 237

A

(B) The gender distribution of CRPS II in the
pediatric population is roughly similar in
boys and girls. Even though patients with
brachial plexus injury during delivery (Erb
palsy) is common and can lead to prolonged
motor weakness, they rarely develop pain.
Interestingly most of these patients do better
without treatment.

Answer 238

A

(B) The diagnosis of CRPS remains a clinical
decision based on findings in the history and
physical examination. There are no laboratory
tests that can absolutely confirm or exclude
the diagnosis. Although controversial, most
of the authors find that bone scans are quite
nonspecific for the diagnosis of CRPS. Patients
with a clinical diagnosis of CRPS may have
bone scans showing hypofixation or hyperfixation
or may be normal. The primary utility
of the bone scan could be in ruling out
some underlying orthopedic abnormality that
might be triggering neurovascular changes
that may confused the findings with those of
CRPS.

Answer 239

A

(C) Movement disorders are an essential feature
of patients with CRPS. Motor dysfunction
is not simply a voluntary defensive response
to protect the limb from painful stimuli, but
may represent the interaction of peripheral and
central mechanisms. Deep tendon reflexes are
often brisk. The prevalence of movement
disorders increases with the duration of the disease.
One characteristic form of these movement
disorders is the presence of inability to
start a movement (akinesia).

Answer 240

A

(A) Dystonia in CRPS patients causes twisting
movements or abnormal postures of the
affected body parts. The most prominent motor
feature is flexor postures (tonic dystonia) of the
fingers, feet, and wrist. Extensor postures occur
but are rare.

Answer 241

A

(E) Supraspinal mechanisms play a major role
in the abnormal sensory perception of patients
with CRPS. Segmental dystonia is characterized
by spread of the cortical representation of
the affected extremity and its corresponding
synaptic connections to adjacent cortical areas.
On the other hand, generalized dystonia have
increased intracortical excitability to sensory
stimuli, and motor cortex disinhibition has
been confirmed in CRPS I. PET scan and SPET
have shown increased activity of the contralateral
thalamus in patients in early stages of
CRPS and hypoperfusion in advanced stages.

Answer 242

A

(C) Myofascial trigger point characteristics:
• Focal severe tenderness in a taut band of
muscle
• Referral of pain to a distant site upon activation
of the trigger point
• Contraction of the taut band (local twitch
response) upon mechanical activation of
the trigger point
• Reproduction of the pain by mechanical
activation of trigger point
• Restriction of range of motion
• Weakness without muscle atrophy
• Autonomic phenomenon such as piloerection
or changes in local circulation (regional
blood flow and limb temperature) in
response to trigger point activation
Individual features of the trigger point are
differentially represented in different muscles.
An examiner should not expect to find each
feature of the trigger point in every muscle by
physical examination.

Answer 243

A

(A) Inactivation of the trigger point is a means
to achieve pain relief, to improve biomechanical
function, and then to improve the ability of
the patient to better perform whatever tasks
have been selected as goals. Relief (not elimination)
of pain or increased range of motion,
both of which can be the result of trigger point
inactivation, are not in themselves the goals of
treatment.

Answer 244

A

(E) While chronic myofascial pain syndrome
is best treated with a multidisciplinary team
approach including the patient, physicians,
psychologists, clinical social workers, occupational
therapists, physical therapists, ergonomists,
massage therapists, and others actively
involved in patient care; patients with acute
myofascial pain syndrome may only require
treatment by physicians and physical therapists.
Too frequently, patients with chronic
myofascial pain are started too soon on isotonic
training and conditioning, causing further
aggravation of active trigger points and an
increase in pain and dysfunction.
The acute treatment plan may be divided
into a pain-control phase and a training or conditioning
phase. During the pain-control phase,
the most essential component is inactivation of
the trigger point. Patients must change their
behaviors and avoid overstressing their muscles
without becoming excessively inactive. The
pain-control phase must have a definitive endpoint.
If patients do not move beyond the paincontrol
phase to the conditioning phase, patients
can be restricted in their functional abilities and
be at greater risk of reinjury. The training or
conditioning phase follows and it involves therapeutic
exercises, movement reeducation, and
overall conditioning

Answer 245

A

(C) Botulinum toxin has been tried successfully
in myofascial trigger point inactivation; however,
it can cause a flu-like myalgia that lasts
days to a week and sporadically causes weakness beyond the area of injection. It functions as a
long-lasting trigger point injection that can provide
up to 3 months of relief in contrast to the
days to 1-week effect of traditional trigger point
injection with local or no anesthetic.

Answer 246

A

(A)
Japanese acupuncture or shallow needling
reduced the pain of chronic myofascial
neck pain in one study.
and 3. These have been found to be true.
While this study does not exist, a technique
of dry needling called intramuscular stimulation
does exist. It involves the insertion of
the needle into the taut band without necessarily
considering the actual trigger
point. It may be combined with electrical
stimulation delivered through the needle
(percutaneous electroneutral stimulation).

Answer 247

A

(D) Fibromyalgia has been found among all
cultures throughout the world with an incidence
of 2% to 12% of the population. In adulthood,
women are affected four to seven times
as often as men. The frequency of fibromyalgia
increases with age and peaks in the seventh
decade of life. In childhood, boys and girls are
affected equally. In contrast to adults, children’s
symptoms may resolve with age.

Answer 248

A

(A) Although research is ongoing, the development
of fibromyalgia appears to be increased
if the patient has had a febrile illness, a history
of physical trauma, or a family history of
fibromyalgia syndrome. Approximately onethird
of patients with fibromyalgia report that
another member of their family has previously
been diagnosed with fibromyalgia

Answer 249

A

(E) Greater than 90% of patients with fibromyalgia
suffer from chronic insomnia. Some patients
may have problems falling asleep. Other may
awaken a few hours after going to sleep and feel
alert, thus disrupting their sleep throughout the
remainder of the night. After a night of sleep,
patients with fibromyalgia may feel stiff, tired,
and “cognitively sluggish.” These patients also encounter difficulty napping throughout the
day. Patients with fibromyalgia have disrupted
sleep architecture with alpha wave intrusions in deep, delta wave sleep.

Answer 250

A

(E)
In fibromyalgia patients, CT has revealed
unusually low cerebral blood flow in the
thalamic nuclei, the left and right heads of
the caudate nucleus, and the cortex that
correlates with spinal fluid substance P
levels.
Windup is a frequency-dependent increase in
the excitability of spinal cord neurons, evoked
by electrical stimulation of afferent C fibers.
Glutamate (NMDA) and tachykinin NK1
receptors are required to generate windup
and therefore a positive modulation between
these two receptor types has been suggested.
Whatever the mechanisms involved in its
generation, windup has been interpreted as a
system for the amplification in the spinal
cord of the nociceptive message that arrives
from peripheral nociceptors connected to C
fibers. This probably reflects the physiological
system activated in the spinal cord after an
intense or persistent barrage of afferent
nociceptive impulses. On the other hand,
windup, central sensitization and hyperalgesia
are not the same phenomena, although
they may share common properties. Spinal
cord windup is abnormal in fibromyalgia
syndrome.
Physical trauma or a fever/infection may
be provisionally related to the onset of
fibromyalgia in over 60% of cases.

Answer 251

A

(B) The levels of serum IL-8 were higher in
fibromyalgia patients, and IL-6 was statistically
higher in cultures of fibromyalgia peripheral
blood mononuclear cells compared with in controls.
The IL-8 increase was most dramatic in
depressed patients, but there was also a correlation
with the duration of fibromyalgia and
the pain intensity. The production of IL-8 in
vitro is stimulated by substance P.

Answer 252

A

(D) Pregabalin has the potential to raise the
threshold for pain fiber depolarization. It is a ligand for the α2δ subunit of voltage-dependent
calcium channel receptors, which has analgesic,
anxiolytic-like, and anticonvulsant activity. It
decreases the release of numerous neuropeptides,
including noradrenaline, glutamate, and
substance P. It has already been approved for
treating partial seizures, pain following the
rash of shingles and pain associated with diabetes
nerve damage (diabetic neuropathy). Two
double-blind, controlled clinical trials, involving
about 1800 patients, support approval for
use in treating fibromyalgia with doses of 300
or 450 mg/d. It is effective in reducing the
severity of body pain, improving quality of
sleep, and reducing fatigue in fibromyalgia
patients. Pregabalin was approved by the FDA
for use in fibromyalgia patients on June 21,
2007.
The most common side effects of pregabalin
include mild to moderate dizziness and
sleepiness. Blurred vision, weight gain, dry
mouth, and swelling of the hands and feet
also were reported in clinical trials. The side
effects appeared to be dose-related. Pregabalin
can impair motor function and cause problems
with concentration and attention. The
FDA advises that patients talk to their doctor
or other health care professional about whether
use of pregabalin may impair their ability to
drive.
Cyclobenzaprine, have been used in the
past with success in fibromyalgia patients,
they have not been approved by the FDA.
Duloxetine is an FDA-approved treatment for
major depression, neuropathic pain from diabetic
peripheral neuropathy, and generalized
anxiety disorder. The drug is a serotonin and
norepinephrine reuptake inhibitor that
exhibits nearly equal serotonin and noradrenaline
reuptake inhibition. Atrial of duloxetine
for patients with chronic pain and/or major
depression indicated that for the fibromyalgia
patients, 80% of the observed effect on pain is
a direct analgesic effect rather than an indirect
antidepressant effect. Common adverse
events were: nausea, headache, dry mouth,
insomnia, constipation, dizziness, fatigue,
somnolence, diarrhea, and hyperhidrosis.
Two placebo-controlled randomized studies
on the treatment of fibromyalgia-associated
pain with duloxetine have been published.
Both studies demonstrated that duloxetine
treatment improved fibromyalgia-associated
pain in women. However, the medication
has not yet been approved for the treatment
of fibromyalgia. Another type of serotonin
and noradrenaline reuptake inhibitor is represented
by milnacipran, where noradrenaline
reuptake inhibition is favored over that
of serotonin. Some reports state that milnacipran
may also be effective in treating
fibromyalgia body pain.
Tramadol has only recently been shown to
improve the pain of patients with fibromyalgia.
It combines weak μ-agonist with
NMDA antagonist and noradrenaline and
serotonin reuptake inhibition. In the combination
preparation that comes with acetaminophen,
a considerable synergy has been
noticed. Nausea and dizziness can be limiting
at first in about 20% of patients, but starting
with just one tablet at bedtime for 1 to
2 weeks can decrease the prevalence and
allow later increases but about one tablet
every 4 days to full therapeutic levels. Atypical
tramadol regimen for fibromyalgia is
300 to 400 mg/d in three or four divided
dosages, concomitant with acetaminophen
at 2 to 3 g/d in divided doses.
Administering 5-hydroxytryptophan can
augment the synthesis of serotonin. Onehundred
milligrams, orally, three times daily
has been shown to be an effective dose in
treating fibromyalgia.

Answer 253

A

(B) Central sensitization can be inhibited by
NMDAreceptor blockade. Two NMDA receptor
antagonists, ketamine and dextromethorphan
(an oral preparation) have been found to
exhibit favorable effects on pain and allodynia
in fibromyalgia patients. With ketamine, 50% of
patients benefited. Fibromyalgia subgroups of
responders and nonresponders were perpetuated
by these findings because all the
fibromyalgia patients in the study were otherwise
comparable. Ketamine’s effectiveness was
limited because of its frequently occurring
psychotropic side effects, such as feelings of unreality, altered body image perception,
aggression, anxiety, nausea, dizziness, and
modulation of hearing and vision.
Dextromethorphan has a better side-effect
profile than ketamine. It was administered
with tramadol to increase the antinociceptive
effect, to hold adverse effects low, and to
decrease the development of opioid tolerance.
A good response was obtained in 58% of the
fibromyalgia patients who tried this regimen.
It may be a consideration for the patients who
respond positively to IV ketamine.

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Chapter 6. Types and Pain Flashcards

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