Treatment of Neuropathic Pain Flashcards
Nociceptive pain
def
Nociceptive pain- Nociception is the transmission of “noxious” stimuli from the sight of injury to the CNS. Nociceptive pain usually the result of damage to normal tissue
Pain is usually “aching” or “throbbing
Responds well to opioids, NSAIDS
Neuropathic pain
def
Neuropathic pain- Results from direct neuronal injury which causes a pathological change in the nerve to promote pain.
Pain is described as burning, “shooting” or “electric-like”
Positive vs. negative symptoms
Therapy often unsuccessful
Pain often effects quality of life (worsened sleep, energy, mood)
Diagnosis based heavily on clinical presentation, history, and exclusion of other causes
Pathophysiology of neuropathic pain
Is characterized as central or peripheral depending upon where the lesion occurs.
Many types of neuropathic pain have BOTH peripheral and central components
Neuropathic pain results from hyper-excitability of either peripheral or central neurons or BOTH
Neuropathic pain
Peripheral vs central
etiology
Peripheral: Diabetic neuropathy Post-herpetic neuralgia Trigeminal neuralgia Chemo-induced HIV induced sensory neuropathy Tumor infiltration neuropathy Phantom limb pain
Central: Post-Stroke Pain Multiple Sclerosis induced pain PD SC injury
Normal pain propagation (pain processing loop)
Painful stimuli carried by nociceptors in the periphery to a collection of cell bodies in the spinal cord known as the dorsal root ganglion
The impulse is carried to the spinalthalamic tract to the cortex for higher processing
The cortex then initiates a complex set of reactions that will ultimately inhibit excitatory impulses Release of NE, 5HT and GABA facilitates inhibition of excitatory impulses.
Overall, the pain processing loop is composed of ascending pain signals and then antinociceptive inhibitory signals
Peripheral sensitization
chars
Inflammatory “soup” causes damage or destruction of peripheral neurons
Neurons become sensitized (lowered threshold)
As regeneration of the nerve occurs, an excess of sodium channels and adrenergic receptors occurs
Peripheral neurons fire impulses spontaneously leading to pain
Sprouting of NEW sodium channels: ENHANCED EXCITATION
Central sensitization
chars
Direct injury to central or peripheral structures may permanently alter sensory processing and lead to pain
Damage can cause a LOSS of inhibition (GABA) producing exaggerated pain response
May be the result of an upregulation of excitatory pathways or a loss of inhibitory pathways leading to excitation
Enhanced transmission via NMDA (N-methyl-D-aspartate) receptor
Glutamate is major excitatory amino acid which activates NMDA receptor
Glutamate binds to the NMDA receptor which causes depolarization and calcium influx into cells
Peripheral Diabetic Neuropathy
Gen chars
5-50% of diabetics experience
Burning, tingling sensations in extremities (usually bilateral)
More than half of all lower extremity amputations due to DN
Loss of sensation
Loss of proprioception
May be due to accumulation of sorbitol into peripheral nerves
Drug induced Neuropathic pain
Anti-retrovirals
Didanosine
Zalcitabine
Stavudine
Up to 30%
Drug-induced neuropathic pain
Cancer chemo
Cisplatin
Vincristine
Paclitaxel
Thalidomide
Up to 80%
Drug-induced neuropathic pain
antibiotics
Metronidazole
INH
Post-herpetic neuralgia
chars
A complication of herpes zoster reactivation (shingles)
Shingles results from reactivation of chickenpox virus
Most commonly occurs in elderly persons
Early antivirals + steroids may decrease severity
Post-herpetic neuralgia is the most common chronic complication of herpes zoster
Defined as pain persisting longer than 1-3months after healing of shingles lesions
Usually pain is self-limiting
Post-herpetic neuralgia
prevention
Vaccine significantly reduced the incidence of shingles by 51%, PHN by 66.5%, and also reduced the severity of pain by 61%.
Most common AE was injection site rash
Contraindicated in patients immunocomprimised (AIDS/cancer chemotherapy) or in patients with allergy to neomycin or gelatin
Trigeminal Neuralgia
chars
Tic douloureux
Multiple sclerosis at increased risk
May be due to compression/demyelinization of 5th cranial nerve
95% of cases are unilateral
Episodes can last for months and then spontaneously go into remission
Trigeminal Neuralgia
Tx options
1st line: Carbamazepine
2nd line: gabapentin, pregabalin, tramadol, opioids (all +/- CBZ)
3rd line: antiepileptic alone or in combination
Approach to pharmacotherapy
Drug regimen is based upon available evidence and safety information
Choice is patient specific- consider co-morbidities, drug interactions
Adequate drug trail needed before considering treatment failure
Initiate at the lowest possible dose
Slowly titrate dose (usually every week)
Titrate one drug at a time
Try combinations for non-responders or partial responders
Re-evaluate therapy after several month
Gabapentin
MOA/adverse events/DDI
MOA:
Binds to alpha 2 delta subunit of Ca channels to decrease excitation
Adverse Events: Dizziness Drowsiness Peripheral Edema Cognitive dysfunction Weight gain
DDI:
Not metabolized thus no DDI
Antacids decrease absorption by 20%
Pregabalin
MOA/adverse events/DDI
MOA:
Binds to alpha 2 delta subunit of Ca channels to decrease excitation
Adverse Events: Dizziness Drowsiness Dry Mouth Cognitive dysfunction Weight gain
DDI:
