Pain Management
Chronic pain syndromes, CRPS, neuraxial opioids, multimodal analgesia, neuropathic pain, interventional pain. ← All topics
Q1. CRPS classification
The defining difference between CRPS type I and type II is:
A. Type I involves severe burning pain while Type II involves moderate aching pain
B. Type I occurs without identifiable nerve injury while Type II occurs after major nerve trunk injury
C. Type I presents in acute phase while Type II presents in chronic phase only
D. Type I affects upper extremity distribution while Type II affects lower extremity distribution
E. Type I has organic etiology while Type II has primarily psychogenic etiology
Show answer
Answer: B. The defining difference between CRPS type I and type II is the presence or absence of an identifiable nerve injury. CRPS I (formerly called reflex sympathetic dystrophy or RSD) occurs after trivial injury without a specific nerve being identified. CRPS II (formerly called causalgia) occurs after a known major nerve trunk injury such as from gunshot wound or surgical trauma. Both types share the same clinical features including burning pain, allodynia, autonomic dysfunction (manifesting as temperature changes, abnormal sweating, and skin color changes), and trophic changes. Treatment modalities are similar for both types and include physical therapy, sympathetic blocks (stellate ganglion block for upper extremity, lumbar sympathetic block for lower extremity), gabapentinoids, tricyclic antidepressants, ketamine infusion, and spinal cord stimulator for refractory cases.
Q2. Neuraxial morphine respiratory depression
Respiratory depression risk after intrathecal morphine peaks at:
A. 30 minutes after injection due to rapid systemic absorption
B. 6–12 hours after injection due to slow cephalad spread
C. 24 hours after injection due to delayed brainstem uptake
D. 48 hours after injection due to prolonged CSF circulation
E. Immediately after injection due to direct medullary exposure
Show answer
Answer: B. Intrathecal morphine is hydrophilic, which causes slow cephalad spread in CSF to reach the brainstem respiratory centers. This results in delayed respiratory depression with peak incidence at 6–12 hours after injection. Patients require monitoring for at least 24 hours postoperatively. In contrast, lipophilic opioids like fentanyl undergo rapid local uptake with peak respiratory depression occurring at the time of injection. ASRA guidelines recommend monitoring for at least 20 minutes continuously then hourly for 2 hours after lipophilic opioids, and hourly for 12 hours then every 2 hours for an additional 12 hours after hydrophilic opioids.
Q3. Multimodal analgesia rationale
The advantage of multimodal analgesia is:
A. Increases total opioid dose and enhances single-pathway analgesia
B. Synergistic effect at multiple pathways reduces total opioid requirement
C. Provides analgesia equivalent to single high-dose opioid administration
D. Increases postoperative nausea and vomiting compared to opioid monotherapy
E. Reduces cost without affecting pain control or opioid consumption
Show answer
Answer: B. Multimodal analgesia targets multiple pain pathways synergistically, reducing total opioid requirements by 30–50%. This approach decreases opioid-related side effects including PONV, constipation, and sedation, and may reduce transition to chronic pain. Common agents include acetaminophen, NSAIDs, gabapentinoids, regional anesthesia, low-dose ketamine, and dexmedetomidine. Multimodal analgesia is a cornerstone of Enhanced Recovery After Surgery (ERAS) protocols and consistently demonstrates better patient outcomes compared to opioid-based monotherapy.
Q4. Methadone for chronic pain
Methadone is useful for chronic neuropathic pain because of:
A. Strong α-adrenergic blockade with peripheral vasodilation and sympathetic modulation
B. NMDA receptor antagonism with μ-opioid agonism and serotonin-norepinephrine reuptake inhibition
C. Cyclooxygenase inhibition with prostaglandin suppression and direct anti-inflammatory activity
D. Neurotrophic factor stimulation with axonal regeneration and myelin sheath repair
E. GABA-A receptor agonism with chloride channel modulation and neuronal hyperpolarization
Show answer
Answer: B. Methadone has a unique combination of three mechanisms that make it particularly effective for chronic neuropathic pain: NMDA receptor antagonism (which addresses neuropathic pain pathways), μ-opioid receptor agonism (providing traditional opioid analgesia), and serotonin-norepinephrine reuptake inhibition (SNRI properties that enhance descending pain modulation). This multimodal profile makes it especially useful in patients with opioid tolerance and neuropathic pain conditions. Important side effects include QT interval prolongation and a long, unpredictable half-life ranging from 13 to 58 hours, necessitating careful titration to avoid accumulation and toxicity.
Q5. Buprenorphine in chronic pain
A patient on buprenorphine for opioid use disorder presents for major surgery. The most current recommendation is:
A. Stop buprenorphine 1 week preoperatively to allow full opioid receptor availability for postoperative pain control
B. Continue buprenorphine perioperatively with multimodal analgesia and add full-agonist opioids at higher than usual doses
C. Switch to methadone preoperatively to provide better postoperative analgesia with a longer-acting opioid agonist
D. Use naloxone postoperatively to reverse buprenorphine and allow full-agonist opioids to provide adequate pain control
E. Avoid all opioids perioperatively and rely exclusively on regional anesthesia and non-opioid multimodal analgesia
Show answer
Answer: B. Current ASAM and ASRA recommendations (2021) favor continuing buprenorphine perioperatively. The approach includes multimodal analgesia with regional techniques when possible. If additional opioid analgesia is needed, full-agonist opioids should be added at higher-than-usual doses because buprenorphine's high mu-receptor affinity and partial agonist properties cause it to displace other opioids, requiring increased dosing to achieve adequate analgesia. Hydromorphone and fentanyl tend to work better than morphine in this setting. Stopping buprenorphine preoperatively should be avoided as it increases the risk of relapse to substance use and worsens postoperative pain control. Switching to methadone or using naloxone are not recommended strategies, and avoiding all opioids is not realistic for major surgery when buprenorphine alone may be insufficient.
Q6. Opioid-induced hyperalgesia
Opioid-induced hyperalgesia is characterized by:
A. Development of tolerance requiring higher opioid doses to achieve the same analgesic effect over time
B. Paradoxical increased sensitivity to pain that worsens with escalating opioid doses and spreads diffusely
C. Acute withdrawal syndrome with autonomic hyperactivity occurring after abrupt cessation of chronic opioid therapy
D. Immune-mediated hypersensitivity reaction with histamine release occurring shortly after opioid administration
E. Dose-dependent central respiratory depression with decreased minute ventilation and hypercapnia during opioid therapy
Show answer
Answer: B. Opioid-induced hyperalgesia (OIH) is a paradoxical state of increased pain sensitivity that occurs with opioid administration and worsens with escalating doses. The pain is often diffuse and extends beyond the original pain area. The mechanism involves NMDA receptor upregulation, dynorphin release, and descending facilitation pathways. Treatment strategies include opioid rotation (especially to methadone, which has NMDA antagonist properties), dose reduction, addition of ketamine, and multimodal analgesia with regional techniques. This differs from tolerance, which requires higher doses for the same effect but does not cause worsening pain, and from withdrawal, which occurs with dose reduction or cessation.
Q7. Ketamine for chronic pain
Low-dose ketamine for chronic neuropathic pain works via:
A. μ-opioid receptor agonism leading to descending inhibition of pain pathways
B. NMDA receptor antagonism leading to modulation of central sensitization and wind-up
C. α₂-adrenergic receptor agonism leading to inhibition of sympathetic pain transmission
D. GABA-A receptor potentiation leading to enhanced inhibitory neurotransmission in dorsal horn
E. Cyclooxygenase inhibition leading to reduced prostaglandin synthesis and peripheral sensitization
Show answer
Answer: B. Low-dose ketamine works via NMDA receptor antagonism, which reverses central sensitization and reduces wind-up phenomena in chronic neuropathic pain. Typical infusion doses range from 0.1 to 0.5 mg/kg/hr and have been shown to reduce opioid consumption in opioid-tolerant patients, treat complex regional pain syndrome (CRPS), and manage various chronic neuropathic pain conditions. Side effects include dissociation, hypertension, and hallucinations, though these are less common at sub-dissociative doses. Ketamine does not work primarily through opioid, adrenergic, GABAergic, or cyclooxygenase mechanisms for its chronic pain effects.
Q8. Tricyclic antidepressants for neuropathic pain
TCAs (amitriptyline, nortriptyline) treat neuropathic pain via:
A. Direct sodium channel blockade in peripheral nerves reducing ectopic discharge
B. Inhibition of serotonin and norepinephrine reuptake enhancing descending pain inhibition
C. NMDA receptor antagonism in the dorsal horn reducing central sensitization
D. μ-opioid receptor agonism in the periaqueductal gray modulating pain transmission
E. GABA-A receptor agonism in the spinal cord increasing inhibitory tone
Show answer
Answer: B. TCAs treat neuropathic pain primarily by inhibiting reuptake of serotonin and norepinephrine, which enhances descending inhibitory pathways that modulate pain transmission in the spinal cord. TCAs are first-line agents for many neuropathic pain conditions including diabetic neuropathy, post-herpetic neuralgia, and fibromyalgia. Common side effects include anticholinergic effects (dry mouth, constipation, urinary retention), sedation, QT prolongation, and orthostatic hypotension. Nortriptyline is generally better tolerated than amitriptyline due to fewer anticholinergic effects. While TCAs do have some sodium channel blocking properties, this is not their primary mechanism for neuropathic pain relief.
Q9. Fibromyalgia treatment
First-line pharmacologic treatment for fibromyalgia includes:
A. Opioid analgesics such as oxycodone or tramadol for chronic pain management
B. Duloxetine, milnacipran, pregabalin, and tricyclic antidepressants like amitriptyline
C. Nonsteroidal anti-inflammatory drugs as monotherapy without adjunctive agents
D. Systemic corticosteroids such as prednisone or methylprednisolone for inflammation
E. Benzodiazepines such as diazepam or clonazepam for muscle relaxation
Show answer
Answer: B. First-line pharmacologic treatment for fibromyalgia includes three FDA-approved medications: duloxetine and milnacipran (both SNRIs) and pregabalin (an alpha-2-delta ligand). Tricyclic antidepressants such as amitriptyline are also effective despite lacking FDA approval for this indication. Pharmacologic therapy should be combined with non-pharmacologic approaches including aerobic exercise, cognitive behavioral therapy, and sleep hygiene. Opioids are generally avoided due to limited efficacy and abuse potential. NSAIDs alone, corticosteroids, and benzodiazepines are not considered first-line treatments for fibromyalgia.
Q10. Lumbar sympathectomy CRPS
Lumbar sympathectomy is appropriate for CRPS of the:
A. Upper extremity, targeting the cervical sympathetic chain
B. Lower extremity, targeting the lumbar sympathetic chain
C. Face, targeting the stellate ganglion and cervical chain
D. Trunk, targeting the thoracic sympathetic chain bilaterally
E. Both upper and lower extremities using combined approaches
Show answer
Answer: B. Lumbar sympathectomy targets the lumbar sympathetic chain (L2–L4) and is appropriate for lower extremity CRPS, as well as peripheral vascular disease, ischemic ulcers, and phantom limb pain. The procedure is typically performed with the patient in prone or lateral position, with the needle advanced to the lateral aspect of the L3 vertebral body, walked off the edge, and advanced approximately 0.5 inch before injecting 12–15 mL of local anesthetic. Upper extremity CRPS would require stellate ganglion block or upper thoracic sympathetic block, not lumbar sympathectomy. Complications of lumbar sympathectomy include genitofemoral neuralgia, intravascular injection, and epidural or intrathecal spread of local anesthetic.
Q11. Intrathecal drug delivery
The most common intrathecal medications delivered via implanted pump include:
A. Morphine, hydromorphone, fentanyl, bupivacaine, clonidine, and ziconotide
B. Baclofen, diazepam, midazolam, dantrolene, tizanidine, and cyclobenzaprine
C. Ketamine, methadone, sufentanil, ropivacaine, dexmedetomidine, and gabapentin
D. Lidocaine, mepivacaine, prilocaine, etidocaine, chloroprocaine, and tetracaine
E. Methotrexate, cytarabine, hydrocortisone, thiotepa, rituximab, and trastuzumab
Show answer
Answer: A. Intrathecal drug delivery (ITDD) via implanted pump is used for refractory chronic pain or severe spasticity (baclofen). The most commonly delivered intrathecal analgesic medications include morphine, hydromorphone, fentanyl, bupivacaine, clonidine, and ziconotide. According to Polyanalgesic Consensus Conference guidelines, morphine and ziconotide are recommended as first-line agents for nociceptive and neuropathic pain respectively. Ziconotide is an N-type calcium channel blocker derived from cone snail toxin that provides analgesia without respiratory depression, though it carries risks of psychiatric and CNS side effects. Baclofen is the primary agent for spasticity but is not typically combined with analgesics in the same pump. The other options represent medications used via different routes or for different indications (chemotherapy agents, oral muscle relaxants, systemic local anesthetics).
Q12. Phantom limb pain treatment
Phantom limb pain prevention may be reduced by:
A. Perioperative regional anesthesia continued postoperatively, gabapentinoid therapy, and mirror visual feedback therapy
B. Intraoperative opioid analgesia alone without adjunctive regional or multimodal preventive interventions
C. Avoidance of neuraxial and peripheral nerve blockade with reliance on systemic analgesics only
D. Nonsteroidal anti-inflammatory drug monotherapy without opioid or neuropathic pain medication adjuncts
E. Selective serotonin reuptake inhibitor monotherapy initiated in the immediate perioperative period
Show answer
Answer: A. Perioperative regional analgesia (epidural or peripheral nerve block) continued into the postoperative period may reduce chronic phantom limb pain, though evidence remains mixed. Gabapentinoids (gabapentin or pregabalin) target neuropathic pain mechanisms. Mirror visual feedback therapy provides cortical remapping through visual input. Additional evidence-based treatments include tricyclic antidepressants, transcutaneous electrical nerve stimulation, and NMDA receptor antagonists such as memantine and ketamine. Spinal cord stimulation is reserved for refractory cases. Opioids alone, NSAIDs alone, and SSRIs lack evidence for phantom limb pain prevention. Avoidance of regional anesthesia is contraindicated as regional techniques may provide protective effects.
Q13. Cancer pain — WHO ladder
Step 3 of the WHO cancer pain ladder includes:
A. Acetaminophen or NSAIDs alone without opioids for mild pain
B. Strong opioid with optional non-opioid and adjuvant for severe pain
C. Tramadol or codeine with optional non-opioid for moderate pain
D. Weak opioid alone without non-opioid or adjuvant therapy
E. Adjuvant medications alone without opioid or non-opioid analgesics
Show answer
Answer: B. The WHO analgesic ladder for cancer pain has three steps. Step 1 (mild pain) uses non-opioid analgesics such as acetaminophen or NSAIDs, with optional adjuvants. Step 2 (moderate pain) uses weak opioids such as tramadol, codeine, or hydrocodone, with optional non-opioid and adjuvant medications. Step 3 (severe pain) uses strong opioids such as morphine, oxycodone, hydromorphone, methadone, or fentanyl, with optional non-opioid and adjuvant medications. Adjuvants include tricyclic antidepressants, gabapentinoids, bisphosphonates for bone metastases, and corticosteroids for edema or mass effect.
Q14. Lidocaine infusion for chronic pain
IV lidocaine infusion for chronic neuropathic pain works via:
A. Selective sodium channel blockade of ectopic neuronal discharge from injured nerves
B. Non-competitive NMDA receptor antagonism at the phencyclidine binding site in dorsal horn
C. GABA-A receptor agonism with enhancement of inhibitory chloride conductance in spinal cord
D. Mu-opioid receptor agonism with activation of descending inhibitory pain pathways centrally
E. Histamine H1 and H2 receptor blockade with reduction of peripheral inflammatory mediators
Show answer
Answer: A. IV lidocaine infusion (typically 1–3 mg/min) works primarily through selective sodium channel blockade of ectopic neuronal discharge from injured nerves, which modulates central sensitization and wind-up phenomena. This mechanism makes it particularly effective for chronic regional pain syndrome (CRPS), neuropathic pain, and refractory cancer pain. Lidocaine does not work via NMDA antagonism, GABA agonism, opioid receptor activation, or histamine blockade. When administering IV lidocaine infusions, toxicity monitoring is essential, with serum levels ideally maintained below 5 mcg/mL to avoid central nervous system and cardiac toxicity.
Q15. Postherpetic neuralgia
First-line therapy for postherpetic neuralgia includes:
A. Topical lidocaine patches, gabapentinoids, and tricyclic antidepressants
B. Antiviral agents such as acyclovir or valacyclovir monotherapy
C. Opioid analgesics as monotherapy without adjuvant medications
D. Systemic corticosteroids alone without other pharmacologic agents
E. Nonsteroidal anti-inflammatory drugs as primary treatment modality
Show answer
Answer: A. First-line therapy for postherpetic neuralgia includes 5% lidocaine patches, gabapentinoids (gabapentin or pregabalin), and tricyclic antidepressants, with nortriptyline preferred over amitriptyline due to better tolerability and fewer anticholinergic side effects. Second-line options include opioids and capsaicin. Antiviral therapy (acyclovir, valacyclovir, famciclovir) is appropriate for acute herpes zoster and can reduce but does not eliminate the risk of developing postherpetic neuralgia. Prevention strategies include zoster vaccination in older adults. NSAIDs and corticosteroids are not considered first-line treatments for established postherpetic neuralgia, though steroids may have a role in acute zoster management.
Q16. Migraine headache treatment
Status migrainosus first-line treatment includes:
A. Opioid analgesics as primary therapy to abort the acute migraine attack and prevent recurrence
B. IV ketorolac, prochlorperazine or metoclopramide, IV fluids, magnesium, and dexamethasone; triptans if not contraindicated
C. Benzodiazepines as monotherapy to provide sedation and reduce anxiety associated with the migraine episode
D. Corticosteroids alone without additional antiemetic, analgesic, or fluid therapy for the acute migraine attack
E. β-blockers administered acutely to abort the migraine attack and provide immediate symptom relief
Show answer
Answer: B. Status migrainosus is a debilitating migraine lasting more than 72 hours and requires aggressive multimodal therapy. First-line treatment includes IV fluids for hydration, NSAIDs (such as ketorolac), antiemetics with D2 antagonist properties (prochlorperazine or metoclopramide, which also have direct anti-migraine effects), magnesium, and dexamethasone to prevent recurrence. Triptans may be used if not contraindicated by coronary artery disease, basilar migraine, or hemiplegic migraine. Opioids should be avoided due to risk of rebound headache and medication overuse. β-blockers are used for prophylaxis, not acute treatment. Benzodiazepines are not first-line therapy. Steroids alone are insufficient without the other components of multimodal therapy. For refractory cases, sphenopalatine ganglion block may be considered.
Q17. Epidural steroid injection for radiculopathy
The best evidence for epidural steroid injection is for:
A. Mechanical low back pain without radicular symptoms (short-term improvement)
B. Lumbar radiculopathy from disc herniation (short-term improvement)
C. Lumbar spinal stenosis with neurogenic claudication (short-term improvement)
D. Facet joint-mediated axial low back pain (short-term improvement)
E. Sacroiliac joint dysfunction with referred pain (short-term improvement)
Show answer
Answer: B. The best evidence for epidural steroid injection is for lumbar radiculopathy from disc herniation, providing short-term pain reduction (typically 1–3 months) with minimal long-term benefit. Evidence for spinal stenosis is more controversial and shows limited benefit. Mechanical low back pain alone, facet joint pain, and sacroiliac dysfunction do not have good evidence supporting epidural steroid injection. Three approaches exist: interlaminar, transforaminal (better target specificity but higher risk of vascular complications), and caudal. Common steroids include triamcinolone or dexamethasone. Major risks include epidural hematoma (especially in anticoagulated patients), infection, and intravascular injection with transforaminal approach (paraplegia risk if particulate steroid enters the radicular artery).
Q18. Trigeminal neuralgia
First-line pharmacotherapy for trigeminal neuralgia is:
A. Opioid analgesics
B. Carbamazepine or oxcarbazepine
C. Acetaminophen
D. Nonsteroidal anti-inflammatory drugs
E. Tricyclic antidepressants
Show answer
Answer: B. Carbamazepine is the first-line pharmacotherapy for trigeminal neuralgia with a number needed to treat of approximately 2, making it highly effective for this neuropathic pain condition. Oxcarbazepine is an acceptable alternative with fewer drug interactions. Important side effects of carbamazepine include hyponatremia, neutropenia, and significant cytochrome P450 drug interactions. For refractory cases that do not respond to medical management, surgical options include microvascular decompression (Janetta procedure), gamma knife radiosurgery, and radiofrequency rhizotomy. Opioids, acetaminophen, and NSAIDs are generally ineffective for neuropathic pain. While tricyclic antidepressants can be used for some neuropathic pain conditions, they are not first-line for trigeminal neuralgia.
Q19. Acetaminophen mechanism
Acetaminophen is now thought to provide analgesia primarily via:
A. Peripheral COX inhibition with significant anti-inflammatory effect
B. Central COX-2 inhibition with serotonergic and cannabinoid modulation
C. NMDA receptor antagonism with secondary glutamate pathway modulation
D. μ-opioid receptor agonism with descending inhibitory pathway activation
E. GABA potentiation with enhanced chloride channel conductance
Show answer
Answer: B. Acetaminophen acts centrally via COX-2 inhibition, with possible activation of descending serotonergic pathways and indirect cannabinoid effects. It has limited peripheral COX inhibition, which explains its lack of anti-inflammatory effect and fewer GI, renal, and platelet side effects compared to NSAIDs. Hepatic toxicity occurs via CYP2E1 metabolism producing NAPQI, which depletes glutathione. Maximum dosing is 4 g/day in adults (3 g/day in chronic alcohol use or hepatic disease).
Q20. Liposomal bupivacaine
Liposomal bupivacaine (Exparel) is intended to provide:
A. 24-hour pain relief through conventional local anesthetic diffusion
B. 72-hour analgesia through slow release from liposomal vesicles
C. 48-hour pain relief through extended tissue binding mechanisms
D. 96-hour analgesia through depot formation at injection site
E. 12-hour pain relief with faster onset than standard bupivacaine
Show answer
Answer: B. Liposomal bupivacaine (Exparel) is formulated to provide 72-hour analgesia through slow release of bupivacaine from multivesicular liposomal carriers. The liposomal encapsulation allows gradual drug release over an extended period. Clinical evidence is mixed, with recent meta-analyses suggesting modest benefit over standard local anesthetics. Cost-effectiveness remains questionable. Important clinical considerations include avoiding combination with other local anesthetics due to potential lipid disruption that can cause premature drug release. FDA-approved indications include surgical site infiltration and interscalene brachial plexus block. The onset time is not faster than standard bupivacaine.
Q21. Myofascial pain syndrome
Diagnostic criteria for myofascial pain syndrome include:
A. Palpable taut band, exquisite tender nodule, reproduction of patient's pain with pressure, and painful limitation of passive range of motion
B. Elevated erythrocyte sedimentation rate, positive antinuclear antibody, elevated C-reactive protein, and abnormal complete blood count with differential
C. Magnetic resonance imaging showing muscle edema, ultrasound demonstrating fascial thickening, and computed tomography revealing soft tissue abnormalities
D. Electromyography demonstrating spontaneous electrical activity, fibrillation potentials, positive sharp waves, and abnormal motor unit action potential recruitment patterns
E. Polymerase chain reaction analysis for collagen mutations, genetic sequencing for sodium channel variants, and chromosomal microarray for structural abnormalities
Show answer
Answer: A. Myofascial pain syndrome is diagnosed clinically based on the presence of trigger points within taut bands of skeletal muscle. The diagnostic criteria include a palpable taut band, an exquisitely tender nodule (trigger point), reproduction of the patient's characteristic pain pattern with pressure on the trigger point, and painful limitation of passive range of motion. No laboratory tests, imaging studies, electromyography, or genetic testing is required or diagnostic for this condition. Treatment options include trigger point injection with local anesthetic, dry needling, botulinum toxin for refractory cases, stretching exercises, physical therapy, and postural correction. Myofascial pain syndrome should be differentiated from fibromyalgia, which presents with widespread tender points without taut bands and represents a more centralized pain processing disorder.