Dolor Neuropatico Cronico Flashcards
QUESTION ONE
A 34-year-old woman with fibromyalgia, generalized anxiety disorder,
and depression is currently taking several psychotropic medications,
including alprazolam, duloxetine, hydrocodone/acetaminophen,
and
pregabalin. She continues to have residual pain, anxiety, and mood
symptoms. Her clinician is considering simplifying her medication
regimen and plans to discontinue the medication with the least evidence
of efficacy for her disorders. Which of the following should
be discontinued?
A. Alprazolam
B. Duloxetine
C. Hydrocodone/acetaminophen
D. Pregabalin
A – Incorrect. Alprazolam is an effective treatment for generalized anxiety
disorder.
B – Incorrect. Duloxetine is an effective treatment for both depression
and for fibromyalgia.
C – Correct. Hydrocodone/acetaminophen does not have evidence of
efficacy for the treatment of fibromyalgia, nor is it an appropriate
treatment for her other illnesses.
D – Incorrect. Pregabalin is an effective treatment for fibromyalgia and
also has evidence of efficacy in anxiety.
QUESTION TWO
A 35-year-old woman complains of widespread pain so debilitating
that she has been unable to work for the last several weeks, though
she did not experience any significant injury that seems to account
for the pain. Specifically, she states that even the mild pressure of
being touched causes such significant pain that she cringes when
her 2-year-old daughter tries to hug her. This type of pain is called:
A. Acute pain
B. Allodynia
C. Hyperalgesia
A – Incorrect. Acute pain refers to pain that resolves after a short duration
and that is usually directly related to tissue damage. In this case
the patient has had significant pain for several weeks despite the
lack of any apparent injury; thus, this does not appear to be acute
pain.
B – Correct. Allodynia is a painful response to a stimulus that does not
normally provoke pain, such as pain in response to light touch.
This is consistent with what the patient describes.
C – Incorrect. Hyperalgesia is an exaggerated pain response to something
that is normally painful (for example, extreme pain in
response to a pin prick). Mild pressure from being hugged by one’s
child would not normally elicit pain, and thus this particular complaint
does not represent hyperalgesia.
QUESTION THREE
A young man arrives at the emergency room in great pain after
receiving a chemical burn during an accident at work. Which primary
afferent neurons would have responded to the chemical stimulus
to produce nociceptive neuronal activity?
A. A-beta fiber neurons
B. A-delta fiber neurons
C. C fiber neurons
A – Incorrect. A-beta fibers respond to non-noxious small movements
such as light touch, hair movement, and vibrations, and do not
respond to noxious stimuli.
B – Incorrect. A-delta fibers fall somewhere in between A-beta fibers
and C fiber neurons, sensing noxious mechanical stimuli and subnoxious
thermal stimuli.
C – Correct. C fiber peripheral terminals are bare nerve endings that
are only activated by noxious mechanical, thermal, or chemical
stimuli. Thus, C fiber neurons are the primary afferent neurons
responsible for nociceptive conduction following this patient’s
injury.
QUESTION FOUR
Pain experienced by patients that is not associated with signs of
neuropathy, but is characterized by hypersensitivity in apparently
normal tissues is called:
A. Inflammatory
B. Neuropathic
C. Nociplastic
D. Nociceptive
A and D – Incorrect. Inflammatory, or nociceptive, pain is pain in
response to an injury or stimulus. Examples of this type of
pain include injuries, bruises, burns, arthritis, and sprains.
B – Incorrect. Neuropathic pain develops when the nervous system is
damaged due to a lesion or disease. Examples of this type of pain
include postherpetic neuralgia, trigeminal neuralgia, neuropathic
low back pain.
C – Correct. In 2018, the International Association for the Study of
Pain (IASP) proposed the term “nociplastic” for pain that results
from altered nociception despite no clear evidence of actual
or threatened tissue damage or evidence of a lesion or disease.
Nociplastic pain is chronic, and types of nociplastic pain include
fibromyalgia,
irritable bowel syndrome, complex regional pain
syndrome, and nonspecific chronic low back pain.
QUESTION FIVE
A 29-year-old woman has just been diagnosed with major depressive
disorder and is being prescribed a selective serotonin reuptake
inhibitor (SSRI). In addition to depressed mood, lack of interest in
her work or friends, and difficulty sleeping, she has been experiencing
aches and pains in her arms, shoulders, and torso. She asks if
the SSRI is likely to alleviate her painful physical symptoms as well
as her emotional ones. Which of the following statements is true?
A. SSRIs may have inconsistent effects on pain because serotonin
can both inhibit and facilitate ascending nociceptive signals
B. SSRIs may worsen pain because serotonin can facilitate but not
inhibit ascending nociceptive signals
C. SSRIs generally alleviate pain because serotonin can inhibit but
not facilitate ascending nociceptive signals
D. SSRIs generally have no effect
on pain because serotonin neither
facilitates nor inhibits nociceptive signals
Two important descending pathways that inhibit ascending nociceptive
signals are the noradrenergic and the serotonergic pathways. Thus,
enhancement of neurotransmission in either of these pathways could
contribute to alleviation of chronic pain.
However, serotonin is also a major neurotransmitter in descending facilitation
pathways to the spinal cord. The combination of both inhibitory
and facilitatory actions of serotonin may explain why SSRIs seem to
have inconsistent effects on painful somatic symptoms.
A – Correct. SSRIs may have inconsistent effects on pain because serotonin
can both inhibit and facilitate ascending nociceptive signals.
B, C, and D – Incorrect
QUESTION SIX
A 22-year-old woman with pain throughout her body, extreme
fatigue, and poor sleep is diagnosed with fibromyalgia. Her care provider
considers prescribing pregabalin, which may alleviate pain by:
A. Binding to the closed conformation of voltage-sensitive sodium
channels
B. Binding to the open conformation of voltage-sensitive sodium
channels
C. Binding to the closed conformation of voltage-sensitive calcium
channels
D. Binding to the open conformation of voltage-sensitive calcium
channels
A and B – Incorrect. Both voltage-sensitive sodium channels and voltage-
sensitive calcium channels (VSCCs) are involved in
transmission of pain; however, pregabalin does not bind to
voltage-sensitive sodium channels in any conformation.
C – Incorrect. This molecular action predicts more affinity for VSCCs
that are actively conducting neuronal impulses within the pain
pathway, and thus a selective action on those VSCCs causing
neuropathic pain, ignoring other VSCCs that are closed, and thus
not interfering with normal neurotransmission in central neurons
uninvolved in mediating the pathological pain state.
D – Correct. Pregabalin does, however, bind to the alpha 2 delta subunit
of VSCCs. In fact, pregabalin binds preferentially to the open
conformation of these channels and thus may be particularly effective
in blocking channels that are the most active, with a “use-dependent”
form of inhibition.
QUESTION SEVEN
A 34-year-old man with juvenile-onset diabetes has begun experiencing
throbbing pain, particularly at night. In addition, he states
that his body generally feels sensitive all over, so that even the brush
of his clothes against his skin can be uncomfortable. These symptoms,
indicative of diabetic peripheral neuropathy, may be caused by:
A. Inflammation or damage in the periphery without disturbance
in central pain processing
B. Central disturbance in pain processing without damage in the
periphery
C. Inflammation or damage in the periphery combined with central
disturbance in pain processing
A and B – Incorrect.
C – Correct. Chronic pain syndromes may be peripheral, central, or
both peripheral and central (“mixed”) in origin. Over time, diabetes
can cause inflammation that damages peripheral nerves and
thus leads to painful physical symptoms. In addition, that damage
may cause repetitive activation of nociception, and such ongoing
neuronal activity may induce central plasticity within the pain
pathway, with progressive and potentially irreversible molecular
changes in pain processing pathways eventually leading to progressive
and potentially irreversible pain symptoms. Thus, diabetic
peripheral neuropathy is a syndrome in which definite peripheral
injury is combined with central sensitization.
QUESTION EIGHT
A 34-year-old man presents with chronic back pain and a major
depressive episode. Which of the following are documented to treat
both chronic central pain and depression without significant side
effects?
A. Amitriptyline
B. Duloxetine
C. Gabapentin
D. Sertraline
A – Incorrect. Although effective for depression and chronic pain, tricyclic
antidepressants such as amitriptyline have several unwanted
mechanisms. Histamine 1 receptor blockade causes sedation and
may lead to weight gain. Muscarinic M1 receptor blockade causes
dry mouth, blurred vision, urinary retention, and constipation; and
muscarinic M3 receptor blockade can interfere with insulin action.
Alpha 1 adrenergic receptor blockade causes orthostatic hypotension
and dizziness.
B – Correct. Duloxetine, a serotonin norepinephrine reuptake inhibitor
(SNRI), may be the antidepressant that is best documented to
have efficacy in pain conditions. Duloxetine targets both descending
noradrenergic and serotonergic projections and the patient
may benefit from an antidepressant with dual mechanisms, which
may help alleviate his chronic pain.
C – Incorrect. Gabapentin, an alpha 2 delta ligand, is not documented
to show efficacy in the treatment of depression.
D – Incorrect. Sertraline, a selective serotonin reuptake inhibitor
(SSRI), is not documented to treat chronic central pain. It is also
possible that the patient may benefit instead from an antidepressant
treatment with dual mechanisms, particularly one with noradrenergic
properties, which may help alleviate his chronic pain.
QUESTION NINE
A 36-year-old woman has just been diagnosed with fibromyalgia.
In addition to her painful physical symptoms, she is experiencing
problems with memory and significant difficulty concentrating at
work. Which of the following may be most likely to alleviate both
her physical pain and her cognitive symptoms?
A. Bupropion
B. Cyclobenzaprine
C. Milnacipran
D. Pregabalin
Documented mechanisms for alleviating central neuropathic pain
include enhancement of serotonergic and noradrenergic neurotransmission
in descending spinal pathways as well as reduction of calcium
influx in pain pathways. Cognitive dysfunction may be alleviated by
increasing dopaminergic (and possibly noradrenergic) neurotransmission
in the dorsolateral prefrontal cortex.
A – Incorrect. Bupropion is a norepinephrine and dopamine reuptake
inhibitor (NDRI) and may reduce cognitive symptoms associated
with fibromyalgia when used as adjunct but is not documented to
reduce pain.
B – Incorrect. Cyclobenzaprine is a muscle relaxant and may be used
for fibromyalgia but is not generally a first-line choice and does
not have efficacy for cognitive symptoms.
C – Correct. Milnacipran is a serotonin norepinephrine reuptake
inhibitor (SNRI) with documented efficacy for treating neuropathic
pain. In addition, it can also improve cognitive symptoms
through its potent norepinephrine reuptake binding property.
D – Incorrect. Pregabalin binds to the alpha 2 delta subunit of voltage-
sensitive calcium channels to reduce calcium influx. It has
documented efficacy for treating neuropathic pain but is not documented
to reduce cognitive symptoms.
QUESTION TEN
A 44-year-old male patient with chronic hepatitis is seeking treatment
for chronic neuropathic pain. Which of the following would
you most likely avoid prescribing for this patient?
A. Duloxetine
B. Gabapentin
C. Pregabalin
All of these medications can be effective for chronic neuropathic pain;
what distinguishes them here is their effects in hepatic impairment.
A – Correct. Duloxetine increases the risk of elevation of serum transaminase
levels and is not recommended for use in individuals with
hepatic insufficiency; thus, it would not be recommended in this
case.
B and C – Incorrect. Gabapentin and pregabalin are not metabolized
by the liver, nor do they appear to have effects on liver functioning;
thus, they are considered safe in hepatic impairment
and do not generally require dose adjustment
QUESTION ELEVEN
Sarah is a 42-year-old patient with long-standing abdominal pain
attributed to Crohn’s disease, as well as low back pain with associated
insomnia and depression. She is currently on 30 mg oral
methadone three times a day, 60 mg duloxetine once a day, and
10 mg desipramine at bedtime. Which of the following opioid
analgesic drugs may have the lowest risk for Sarah developing serotonin
syndrome?
A. Meperidine
B. Methadone
C. Morphine
D. Tramadol
In the presence of other serotonergic agents, opioids may significantly
affect serotonin kinetics, causing increased intrasynaptic serotonin
levels, which can lead to the development of serotonin syndrome. In
March 2016, the US Food and Drug Administration (FDA) issued a
warning about the potential interaction between opioids and antidepressants
and the development of serotonin syndrome.
A – Incorrect. Meperidine is a potent inhibitor of serotonin reuptake
and toxic reactions have been known to occur when meperidine
is given to patients on monoamine oxidase inhibitor (MAOI) or
tricyclic antidepressant therapy.
B – Incorrect. Methadone has an inhibitory effect on serotonin transporters.
Serotonin syndrome has been reported in a few cases
when methadone therapy is co-administered with a selective serotonin
reuptake inhibitor (SSRI).
C – Correct. Certain synthetic opioids such as tramadol, methadone,
meperidine, fentanyl, and dextromethorphan are weak serotonin
reuptake inhibitors and can cause toxicity, but opioids with a structure
similar to morphine are not reuptake inhibitors and may be
less likely to cause serotonin syndrome (or serotonin toxicity).
D – Incorrect. Tramadol is a racemic mixture of R and S enantiomers.
The R enantiomer is a mu-opioid receptor agonist, while the S
enantiomer inhibits reuptake of norepinephrine and releases serotonin,
which results in an excess of intrasynaptic serotonin when
combined with other serotonergic drugs.
The list of clinical features for serotonin syndrome, ranging from
mild to severe, is often viewed as a triad of changes in neuromuscular
hyperactivity (clonus, hyperreflexia, myoclonus, and rigidity
in advanced stages of toxicity), autonomic nervous system hyperactivity
(hyperthermia, tachycardia, diaphoresis, and mydriasis), and
changes in mental status (agitation, excitement, restlessness, and
confusion in advanced stages).
QUESTION TWELVE
Which of the following statements about the use of antidepressants
for pain management is correct?
A. They relieve pain primarily in patients with depression
B. They relieve pain at higher doses than those used for an antidepressant
effect
C. They may relieve pain by blocking receptors for serotonin and
norepinephrine in the central nervous system (CNS)
D. They may relieve pain by blocking the reuptake of serotonin
and norepinephrine in the CNS
A – Incorrect. Antidepressants have not been shown to provide more
relief for patients with depression compared to others.
B – Incorrect. The doses for antidepressants that are effective for pain
are generally lower than the doses used for depression.
C – Incorrect.
D – Correct. The mechanism of action of the antidepressants is that they
inhibit the reuptake of the biogenic amines, mostly norepinephrine
as well as serotonin, which hypothetically increases the presence of
these neurotransmitters to increase nociceptive inhibition
