ICL 7.4: Neuropathic Pain

Question 1

what is neuropathic pain?

Answer 1

pain arising from a lesion or disease of the somatosensory nervous system – mechanism is poorly understood

the somatosensory system is the part of the sensory system concerned with the conscious perception of touch, pressure, pain, temperature, position, movement, and vibration, which arise from the muscles, joints, skin, and fascia

it’s due to damage to the nervous system!

it feels like burning and lancinating pain that may be spontaneous or evoked with light touch

so it’s different than nociceptive pain that’s from injuries

Question 2

what are the characteristics of neuropathic pain?

Answer 2

1. pain may be in the distribution of a nerve or dermatome
2. abnormal spontaneous non-painful sensations (paresthesias) like your arm “going to sleep”, tingling, pins and needles
3. abnormal spontaneous painful sensations (dysesthesias) like a sunburn; burning, lancinating pain
4. painful mechanical hypersensitivity so even light touch causes pain and painful stimuli are even more painful
5. variabel numbness = hypoesthesia

NP has unusual characteristics, such as painful numbness, and spontaneous burning and lancinating pain

Question 3

what is allodynia?

Answer 3

when light touch causes pain

Question 4

what is hyperalgesia?

Answer 4

when a painful stimulus is more painful

Question 5

how does the somatosensory nervous system generate pain?

Answer 5

1. nervous system injury causes hypersensitivity
2. injured nerves may form neuromas that cause painful discharges (ectopic discharges)
3. injured dorsal root ganglia in spinal cord may cause painful discharges
4. descending pain control pathways enhance pain

Question 6

what is the pathophysiology of how peripheral changes in primary afferent nerves cause neuropathic pain?

Answer 6

1. alterations in sodium channels and calcium channels on sensory nerves
2. increased Nerve Growth Factor may promote enhanced pain state
3. increased α-adrenergic receptors on nerve terminals (Complex Regional Pain Syndrome)

Question 7

what is the pathophysiology of how changes in the spinal cord and brain cause neuropathic pain?

Answer 7

1. postsynaptic changes in dorsal horn transmitters - NMDA receptor phosphorylation
2. alterations in interneurons - decreased GABA
3. neurogenic inflammation involving glial cells

Question 8

how does neuroinflammation cause neuropathic pain?

Answer 8

activation of glial immune cells expressing Toll Like Receptors can cause neuroinflammation

however, toll Like Receptor (TLR4) antagonists may reduce allodynia after nerve injury by inhibiting glial cells!

Question 9

which drug can be used to reduce neuroinflammation and reduce neuropathic pain?

Answer 9

naltrexone

(+)-Naltrexone appears to inhibit TLR4 and may provide pain relief at low doses by inhibiting glial cells

naltrexone can be used clinically up to 5 mg per day to reduce pain

Question 10

what are some clinical examples of neuropathic pain?

Answer 10

1. painful peripheral neuropathies
   ex. diabetic neuropathy, acute herpes zoster neuralgia, peripheral nerve injury, HIV neuropathy
2. mixed pain syndromes
   ex. spinal radiculopathies, complex regional pain syndrome, cancer
3. central pain syndromes
   ex. post stroke pain, spinal cord injury

Question 11

what is complex regional pain syndrome?

Answer 11

a chronic pain condition that most often affects one limb (arm, leg, hand, or foot) usually after an injury

CRPS is believed to be caused by damage to, or malfunction of, the peripheral and central nervous systems

Question 12

how do anticonvulsants help with neuropathic pain?

Answer 12

“Gabapentinoids” relieve pain by modifying Ca++ channels on nerve fibers and spinal tracts –> they are anticonvulsants that suppress pain fiber activity by binding to Ca+2 channels on nerves and slowing abnormal firing of nerves

so these are NOT helpful for nociceptive pain

other anticonvulsants block Na+ channels

Question 13

which drugs are anticonvulsants that can be used to treat neuropathic pain?

Answer 13

1. Pregabalin (Lyrica)
2. Gabapentin (Neurontin)
3. Carbamazepine (Tegretol); Na+ channel blocker

Question 14

how can antidepressants be used to treat neuropathic pain?

Answer 14

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) increase serotonin and NE at synapses

this reduces central sensitization and enhances descending inhibition

Serotonin Selective Reuptake inhibitors (SSRIs) are NOT helpful

Question 15

which antidepressant drugs are used to treat neuropathic pain?

Answer 15

1. duloxetine (cymbalta)

2. amitriptyline (slavic) –> also has Na+ blocking activity

Question 16

are opioids used for neuropathic pain?

Answer 16

opioids block nociceptive transmission in the spinal cord and brain

research and clinical studies indicate that opioids are NOT very effective for neuropathic pain at normal doses

also damage to the nervous system makes opioids less effective

sometimes, opioids may be effective for some mixed pain states but not first line drugs for NP

Question 17

what are the risk factors for developing diabetic neuropathy?

Answer 17

1. age
2. duration
3. poor glycemic control

50% of diabetics develop peripheral neuropathy over time

Question 18

what kind of pain do patients with diabetic neuropathy experience?

Answer 18

1. symmetric, sensory predominant small fiber neuropathy most common (“stocking and glove” distribution)
2. numbness and paresthesias (burning and stabbing pain)
3. aching in feet and hands

there is preservation of position sense and reflexes

patients without pain more likely to have large fiber neuropathy and they will experience a loss of proprioception

Question 19

how can hyperglycemia with diabetics worsen pain?

Answer 19

1. polyol pathway causes sorbitol and fructose accumulation which then causes nerve injury
2. reduced nitric oxide leads to impaired nerve blood flow
3. reactive oxygen species damage endothelium
4. decreased nerve growth factor
5. glycation of tissue proteins

intensive glycemic control may reduce neuropathy

Question 20

which medications are strongly recommended for diabetic neuropathy?

Answer 20

1. pregabalin
2. duloxetine
3. gabapentin
4. tricyclic antidepressants

DON’T use opioids on diabetic neuropathy because it’s a neuropathic pain, not a nociceptive pain

Question 21

which medications are weakly recommended for diabetic neuropathy?

Answer 21

1. opioids
2. capsaicin
3. lidocaine patches
4. SSRI antidepressants (fluoxetine)

Question 22

what is shingles?

Answer 22

Reactivation of latent varicella-zoster virus (VZV) from the DRG

pain before the rash is tingling and itching = allodynia, burning, lancinting and aching

Question 23

where do people get shingles rash?

Answer 23

1. facial
2. thoracic
3. lumbar

eye involvement indicates referral to ophthalmologist

Question 24

how do you treat herpes zoster?

Answer 24

1. Antivirals
   Valacyclovir; Famciclovir; Acyclovir
2. Analgesics: NSAIDS; Opioids
3. Steroids: Prednisone (with antiviral)
4. Gabapentin
5. Pregabalin
6. Duloxetine

Question 25

what is postherpetic neuralgia?

Answer 25

pain that persists beyond acute phase of shingles (3 months)

allodynia, hyperalgesia; burning pain, lancinating pain

Question 26

which medications can be used to treat postherapetic neuralgia?

Answer 26

1. gabapentin
2. pregabalin
3. duloxetine
4. lidocaine patch
5. tricyclic antidepressants

Question 27

what is a radiculopathy?

Answer 27

a disease of the root of a nerve, such as from a pinched nerve or a tumor

Question 28

is a radiculopathy neuropathic or nociceptive pain?

Answer 28

neuropathic pain

inflamed dorsal root ganglion demonstrate upregulation of opioid receptors, sodium channels and NK1 receptors (similar with Herpes Zoster)

inflamed dorsal root ganglion demonstrates upregulation of opioid receptors, sodium channels and NK1 receptors (similar with Herpes Zoster)

Question 29

how do you conservatively treat a radiculopathy?

Answer 29

1. NSAIDs
2. Gabapentin/Pregabalin
3. Physical therapy
4. Epidural injections
5. Opioid analgesics short term for moderate to severe pain (ex. low dose hydrocodone, oxycodone or tramadol)

Question 30

when would you need to do surgery for a radiculopathy?

Answer 30

persistent pain +/- neurological deficit

1. Usually a neurologic deficit (e.g. weakness or reflex change)
2. Adequate time for healing has passed
3. Risk factors for surgery are appropriate
4. Back pain alone may not be indication for surgery

you could possibly do spinal cord stimulation if surgery doesn’t help or pain gets worse

Question 31

what’s the most common cause of neuropathic pain?

Answer 31

peripheral neuropathies