Chronic pain and its treatment Flashcards
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.
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
D. Neuropathic pain
A Incorrect. Acute pain refers to pain that resolves after a short duration and that is usually
directly related to the healing of 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.
D Incorrect. Neuropathic pain is pain that arises from damage to or dysfunction of any part of the
peripheral or central nervous system. Neuropathic pain is not defined by the degree of pain in
response to a certain type of stimulus, which is what this patient is describing.
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.
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.
B, C, and D Incorrect.
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 and voltage-sensitive calcium channels are
involved in transmission of pain; however, pregabalin does not bind to voltage-sensitive sodium
channels in any conformation.
D Correct. Pregabalin does, however, bind to the alpha 2 delta subunit of voltage-sensitive
calcium channels (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.
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
A 30-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.
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.
A 60-year-old woman was diagnosed with fibromyalgia 1 year ago but has not responded well to
pregabalin, gabapentin, or duloxetine. She is hesitant to take multiple medications and instead hopes to try
a different monotherapy. Of the following options, which is the best choice as a second-line monotherapy
for fibromyalgia?
A. Amitriptyline
B. Atomoxetine
C. Ibuprofen
D. Modafinil
A Correct. Amitriptyline is a tricyclic antidepressant that inhibits both the serotonin and
norepinephrine transporters. Although it is not generally used first-line for fibromyalgia, it does
have documented efficacy in this disorder and is a good second-line option.
B Incorrect. Atomoxetine is a selective norepinephrine reuptake inhibitor (NRI) and may be used
as an adjunct for fibromyalgia, particularly for resolution of cognitive symptoms, but does not
have documented efficacy for pain and would not be a good choice as a monotherapy.
C Incorrect. Ibuprofen is a nonsteroidal anti-inflammatory agent (NSAID) and can be used to
treat pain related to peripheral injury, but it does not have any documented efficacy for
fibromyalgia.
D Incorrect. Modafinil is a wake-promoting agent that seems to affect the histaminergic and
dopaminergic neurotransmitter systems. It may be a useful adjunct for fatigue in fibromyalgia but
does not have documented efficacy for pain.
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
A 28-year-old patient with a long history of painful somatic symptoms has been diagnosed with major
depressive disorder but has not responded to multiple successive trials of selective serotonin reuptake
inhibitors (SSRIs). Her clinician is now considering prescribing a monoamine oxidase inhibitor (MAOI).
Due to her history of chronic pain, she is currently taking an opioid. Which of the following opioids
would be of greatest concern for this patient?
A. Codeine
B. Morphine
C. Hydrocodone
D. Meperidine
There is no interaction of MAOIs with opioid mechanisms; however, some opioids have serotonergic
properties that could increase risk of serotonin syndrome if they were administered together.
A Incorrect. Codeine does not have serotonergic properties and is safe to prescribe with SSRIs.
B Incorrect. Morphine does not have serotonergic properties and is safe to prescribe with SSRIs.
C Incorrect. Hydrocodone does not have serotonergic properties and is safe to prescribe with
SSRIs.
D Correct. Meperidine is a potent serotonin reuptake inhibitor and should not be prescribed with
MAOIs.
