Chronic Pain

Question 1

Protopathic pain fibers

Answer 1

A-delta fibers: myelinated, fast/well-localized pain

C fibers: slow secondary pain

Question 2

Pain transduction pathway

Answer 2

• First order neurons in the periphery with cell bodies in spinal ganglion off posterior (most) nerve root (some enter ventral nerve root)
• Synapse with 2nd order neurons with cell bodies in dorsal horn of SC
• Synapse w/3rd order neurons w/cell bodies in thalamus

Question 3

What is a rhizotomy?

Answer 3

Transection of dorsal nerve root off the spinal cord

Question 4

Major lamina of dorsal horn

Answer 4

Lamina 1: somatic pain
Lamina 2: substantia gelatinosa (interneurons, important for modulating pain, especially somatic pain, densest opioid receptors)
Lamina 5: viceral pain

Question 5

Opioid receptor activation

Answer 5

Hyperpolarizes (inhibits) both pre-synaptic 1st order neurons and post-synaptic 2nd order neurons
*Classic: endogenous opioids act pre-synaptically, exogenous opioids act post-synaptically

Question 6

Nociceptor sensitization v inhibition

Answer 6

Nociceptor sensitization: decreasing threshold for activation; various mediators like PGs, histamine, bradykinin, substance P etc.
-prevent w/NSAIDs, ASA, APAP

Nociceptor activation: blockage of transmission w/LAs

Question 7

Peripheral v central sensitization

Answer 7

Peripheral sensitization: occurs through chemically mediated (BK, PGs, sub P), heat, frequency of stimuli, etc
-leads to decreased threshold for nociceptor stimulation, decreased response latency, and after-discharge phenomenon (spontaneous firing after stimulus is gone)

Central sensitization: due to wind-up and sensitization of 2nd order neurons and WDRs through neurochemical mediators (CGRP, sP, etc), NMDA mechanisms, expansion of receptive field, and others

Question 8

Wind-up

Answer 8

Small response from 1st order neurons leads to a larger response from 2nd order neurons
-NMDA agonism–>increased IC Ca2+–>neurochemical mediators that sensitize 2nd order neurons and increase aspartate and glutamate (which stimulate NMDA receptor)–>positive feedback loop

Question 9

Neurogenic inflammation

Answer 9

“Triple Response”- flushing, edema, and sensitization of nociceptors

Question 10

Mechanisms of neuropathic pain

Answer 10

• Reorganization and expansion of the receptor field for dorsal horn nociceptive (2nd order) fibers
• Spontaneous electrical conduction of a 1st order afferent neuron
• Short-circuits between nociceptive 1st order neurons and other types of neurons
• Decreased activity of supraspinal inhibitory pathways

Question 11

Gabapentin:
MOA
Indications

Answer 11

MOA: alpha-2-delta calcium channel and NMDA receptor

Indications: diabetic neuropathy, post-herpetic neuropathy, fibromyalgia; and off label for phantom limb pain and spinal cord injury
*not effective for CRPS

Question 12

Tramadol MOA

Answer 12

Agonist (weak, but specific) at mu opioid receptor
Increases serotonin release
Decreases norepinephrine uptake
Antagonizes NMDA
Agonist at VR1 (capsaicin) receptor

Question 13

Which intervention during an episode of herpes zoster would most likely prevent post-herpetic neuralgia?

What are other treatments?

Answer 13

Epidural anesthesia- large sympathetic component

Tx: gabapentin, TCA, lidocaine patches, capsaicin, NSAIDs, opioids

Question 14

CRPS pathophysiology progression

Answer 14

Acute pain with increased blood flow (edema, warm, red)–>vasospasm (cold, cyanotic)–>atrophy (osteoporosis, muscle wasting, ankylosing joints, contractors, glossy skin)

Question 15

Early treatment of CRPS

Mainstay

Answer 15

Early: Sympathetic blocks (eg. stellate ganglion)- usually weekly, 3-12 injections
-gabapentin and TCAs often added but don’t prevent progression w/o sympathectomy

Mainstay: PT

Last resorts: ketamine gtt, spinal cord stim

Question 16

Phantom limb pain (PLP) treatment

Answer 16

Pregabalin (FDA approved), clonidine, NMDA antagonists, nerve blocks (avoid spinal anesthesia)

Question 17

Definitions:

• hypoalgesia
• dysaesthesia
• hyperalgesia
• hypoaesthesia
• paresthesia
• anesthesia dolorosa
• allodynia
• hyperpathia

Answer 17

• Hypoalgesia: diminished response to a noxious stimulus
• Dysaesthesia: unpleasant sensation w or w/o stimulus
• Hyperalgesia: increased response to a noxious stimulus
• Hypoaesthesia: reduced epicritic sensation
• Paresthesia: abnl sensation w/o an apparent stimulus
• Anesthesia dolorosa: pain in an area that lacks sensation
• Allodynia: perception of non-noxious (epicritic) sensation as pain
• Hyperpathia: hyperesthesia, hyperalgesia, and allodynia w/overreaction and persistence of pain after the stimulus is gone

Question 18

TENS MOA

Answer 18

Stimulates large afferent epicritic fibers
OR
Conduction blockage of small afferent pain fibers

Gate theory of pain: sending additional noxious or epicritic stimuli to the CNS, the original pain will no longer be as well perceived (rubbing a painful injury, “distracting pain”

Question 19

Stellate Ganglion block

• anatomy
• complications

Answer 19

Anatomy-transverse process of C6 (Chassiaignac’s tubercle)

Complications: Horner’s syndrome (ptosis, miosis, anhidrosis, and nasal stuffiness), and hyperaemia and increased temp of ipsilateral arm

Question 20

Celiac plexus

• vertebral level
• MOA

Answer 20

Vertebral level: L1

MOA: upper abdominal sympathectomy (no motor fibers)

Question 21

Trigeminal nerve block locations

Answer 21

• Gasserian nerve block- found in Meckel’s cave
• Ophthalmic n: at supraoptic notch
• Maxillary n: between zygomatic arch and notch of mandible

Question 22

Geniculate ganglion?

Answer 22

Cell bodies of afferent neurons of facial nerve

• blockade leads to Bell’s palsy
• used to treat herpes zoster of facial nerve

Question 23

Diabetic neuropathy EMG findings

-demyelination or axonal neuropathy

Answer 23

Diabetic neuropathy

• EMG: decreased amplitude, decreased conduction velocities, and prolonged latencies
• both demyelination and axonal neuropathy (mixed)

Demyelination: prolonged latencies and decreased conduction velocities

Axonal neuropathy: decreased amplitude