Neuropathic Pain: Pharmacology

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Neuropathic Pain

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any pain syndrome in which the predominating mechanism is aberrant somatosensory processing in the peripheral nervous system,or CNS.

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Etiologies of Neuropathic pain

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diabetic neuropathy
shingles (herpes zoster ), AIDs
Multiple sclerosis, Cancer
Trigeminal Neuralgia
Sciatica (Back, leg and hip problems)

Alcoholism
Anticancer chemotherapy, radiation therapy
Antiretroviral therapy

Amputation
Spinal Surgery

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Types of Neuropathic Pain

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deafferentation pain

sympathetically maintained pain

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Deafferenation pain and examples

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due to partial or complete interruption of peripheral or central afferent neural activity: pain pathway is interrupted

postherpetic neuralgia
central pain (pain after CNS injury)
phantom pain (missing body part)

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Neuropathic Pain

Back 5

any pain syndrome in which the predominating mechanism is aberrant somatosensory processing in the peripheral nervous system,or CNS.

Front 6

Etiologies of Neuropathic pain

Back 6

diabetic neuropathy
shingles (herpes zoster ), AIDs
Multiple sclerosis, Cancer
Trigeminal Neuralgia
Sciatica (Back, leg and hip problems)

Alcoholism
Anticancer chemotherapy, radiation therapy
Antiretroviral therapy

Amputation
Spinal Surgery

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Types of Neuropathic Pain

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deafferentation pain

sympathetically maintained pain

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Deafferenation pain and examples

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due to partial or complete interruption of peripheral or central afferent neural activity

postherpetic neuralgia
central pain (pain after CNS injury)
phantom pain (missing body part)

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Sympathetically Maintained Pain

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autonomic system maintains

CRPS: complex regional pain syndrome

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A-delta fiber

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1st pain felt, fast

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C fiber

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slow second pain

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CRPS

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chronic pain syndrome, most likely associated with sympathetically maintained pain

associated with autonomic changes (sweating)

can detect temp differ. on skin

May be associated with trophic changes(skin or bone atrophy, hair loss, joints)

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CRPS type I

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soft tissue damage or bone injury

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CRPS type II

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nerve injury (causalgia)

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Note:

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neuropathic pain often exists with conventional (nociceptive) pain

any subtype or neuropathic pain occurs with HIV infection and AIDs: additional pain

with infection and/or antivirals

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Peripheral Neuropathy Induced by Antiretrovirals

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Mainly:
Didanosine
Stavudine
Zalcitabine

Incidence increases with prolonged exposure

Risk Factors
-pre-existing peripheral neuropathy
-combined use of above NRTIs or concomitant use of other drugs
-advanced HIV disease (more pain risk)

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Peripheral Neuropathy Induced by Antiretrovirals: Onset and Symptoms

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weeks to months

initially numbness and paraesthesia of toes and feet BILATERAL annd SYMMETRIC

may progress to painful neuropathy of feet and calf
may be irreversible after discontinuation

(periph neuropathy also seen with Vinca Alkaloids (cancer treatment))

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Peripheral Neuropathy Induce by Antiretrovirals : Prevention and Management

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Prevention/Monitoring:
avoid using in patients with risks (if possible)
Avoid any combination use of ddl, DT4 and DDC
patient query at each encounter

Management:
consider discontinuing offending agent before pain becomes disabling
pharmalogical management

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Pain Assessment

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quality of pain
localization
duration, time-course
Triggers, circumstances
Accessory symptoms (sweating, nausea, etc.)

VAS : visual analog scale 1-10

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Go over Cases in this packet

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pg. 5 and 6

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Gabapentin

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amino acid analogue of GABA

antiepileptic drug

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Gabapentin MOA

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unknown (does NOT bind to GABA receptors)

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Gabapentin PK

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100% oral bioavailability

no metabolism

renal elimination t1/2=5-8hrs

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Gabapentin AE

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somnolence

dizziness

ataxia

tremor

GI

imbalance in blood glucose levels

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Gabapentin USE

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adjunct treatment against partial seizures and generalized clonic tonic seizures

neuropathic paine

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Gabapentin in Neuropathic Pain

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30-40% responders

may prove effective after NSAIDS, opiods, amitryptiline, carbamexepine have failed

start at doses used in antiepileptic therapy
evaluate first response after 5-10 days
if any benefit is seen, escalate dose to limit
full efficacy often seen after weeks to months

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Peripheral Neuropathy Induced by Antiretrovirals: Drug Treatment (NIH guidelines)

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gabapentin (best validated)

tricyclic antidepressants ( in addition)

iamtrigine, oxycarbamaxepine (CYP interaction)

topiramate, tramadol

opioids

capsaicin cream-counter stimulant

topical lidocaine

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Clinically used Analgesic Agents:

Anticonvulsants

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decrease neural excitability

used for neurpathic pain

gabapentin
lamotrigene
phenytoin

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Clinically used Analgeis Agents:

Antiarrhythmics

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decrease neural excitability

used for neuropathic pain

Lidocaine
Mexilitene

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Gate control Circuitry in Spinal Cord

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pg. 8 in packet...look at diagram and I.D. everything

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Clinically used Analgesic Agents:

Antidepressants

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inhibit reuptake of noradrenaline or serotonin used for neuropathic pain

Amitriptyline
Nortriptyline
Fluoxetine
Paroxetine

precautions: serotonin syndrome with SSRIs (class effect)
ritonavir c. fluoxetine
tramadol c. fluoxetine
suicidal risk

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What antideppressant is approved by FDA to use for diabetic neuropathy?

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Duloxetine

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Goals of antidrepessants

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improve ativitity level

improve mood

when activity level has increased but not mood (window for suicide)

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Clinically used Analgesic Agents:

Opioids

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act at the spinal and supraspinal opioid receptor

used for both nociceptive and neuropathic pain

morphine
hydromorphone
fentanyl
codeine

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Clinically Used Analgesic Agents:
Glucocorticoids

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primarily for neuritis, edematous nerve compression syndrome, edema

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Clinically Used Analgesic Agents:

NSAID

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primarily for nociceptive pain

inhibit peripheral and central cyclo-oxygenase

Aspirin
Ibuprofen
Celecoxib

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What sensitizes nociceptors?

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prostaglandins from damaged cells

leukotrienes from damaged cells

substance P from primary afferents

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Nondrug Analgesic Approaches

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Anesthesiology
Neurosurgical
Neurostimulatory
Psychiatric, Psychologic

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Anesthesiolgy

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Intraspinal infusion
neural blockade
treatment of myofascial trigger (lidocaine, saline)

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Neurosurgical

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Neurolysis, plexus ablation (chordotomy)

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Neurostimulatory

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Acupuncture, transcutaneous electrical nerve stimulation (TENS)
counterirritation
capsaicin ro coining