Neuropathic pain

pain caused by dysfunction or lesion of the nervous system. After tissue injury there is a decreased activation threshold of A delta and C fibers. There is also an increase in ion channels. This leads to increased excitability of sensory nerves and dorsal root ganglion cell bodies.

Neuropathic pain is associated with altered processing and changes in central modulation. This includes pathologic activity in injured nerves (resulting in hyperexcitability as well as spontaneous and evoked pain); loss of C fibers; sprouting of the large fibers in the outer laminae of the dorsal horn, where the nociceptive-specific neurons are located (resulting in allodynia); and increased activity in the sympathetic nervous system.

Anticonvulsants – think Na blockers

 Epilepsy is thought to be driven by hyperexcitability of neurons due to sodium and calcium channels.

Phenytoin (Dilantin)

–          Dosing: initial 100mg bid/tid.

–          High medication interaction (Cytochrome P450 activation) and side effect profile limits utility (gum hyperplasia)

–          Mechanism: blocks Na channels à decreases excitatory glutamate release à decreases ectopic discharges

Carbamazepine (Tegretol)

–          Dosing: initial 100-200mg bid. Effective dose 300mg-1200mg.

–          Structure similar to TCAs

–          Na channel blocker – effects active nerves. leaves normal Alpha delta and C fibers alone

–          Use for TRIGEMINAL NEURALGIA

–          Side effects: pancytopenia (lab work every 2-4months)/Steven Johnson Syn/toxic epidermal necrolysis

Oxcarbazepine (Trileptal)

–          Created as a cleaner version of Tegretol

–          Na channel blocker

–          Side effects: Hyponatremia – will need to monitor over first three months at lease

Valproic Acid

–          Na Channel blocker and increases GABA – poorly studied.

–          Has been beneficial in Migraines.

–          Side effects: GI upset, somnolence and dizziness

Lamotrigine (Lamictal)

–          Na channel blocker and prevent glutamate release

–          Use for patients with TRIGEMINAL NEURALGIA that do not respond to Tegretol

–          Side effects: rash

Topiramate (topomax)

–          Does it all! Na Channel blocker, Ca channel blocker, and enhances GABA

–          Dosing: initial 50mg nightly. Effective 200mg qD. Max 200mg tid

–          Side effects: Sedation, Weight loss

Levetiracetam (Keppra)

–          Mechanism of action unknown

–          Dosing: initial 500mg bid. Effective 3000mg/day. Max 5000mg/day

–          Not Cytochrome P450 metabolized – should not interfere with other meds

–          Side effects:  asthenia, dizziness, somnolence, HA

Local Anesthetics

Lidocaine

–          IV – 1-5mg/kg over 30-60minutes

–          Side effects: dizziness, seizures (typically at plasma level of 10mg/ml), bradycardia (antiarrhythmic)

–          Patches – good for postherpetic neuralgia, post-thoracotomy pain, intercostal neuralgia, and meralgia paresthetica

o   EMLA cream = prilocaine +lidocaine

–          Some indications IV lidocaine can be used for perioperative pain management

Mexiletine

–          Dosing: initial 75-150mg/day with target of 300-450mg/day

–          Oral analogue of lidocaine

–          Side effects: nausea, somnolence

Calcium Channel Blocker

–          Bind to alpha-2 delta subunit of L-type voltage gated calcium channels à decrease glutamate, norepi, and substance P

Gabapentin (Neurontin) – no GABA action

–          Dosing: initial 100-300mg/daily. Max dose 3600mg daily

–          Side effects: somnolence, dizziness, fluid retention

–          Combo of gabapentin and TCA reported to be effective for diabetic neuropathy

–          Now scheduled due to increased mortality risk with co-prescription of opioids

Pregabalin (Lyrica) – no GABA action

–          Dosing: 150mg/day with max of 600mg/day

–          Indicated for fibromyalgia – also useful in diabetic neuropathy

–          Side effects – less somnolence and dizziness than gabapentin

Zonisamide (Zonegran)

–          Blocks T-type calcium channels, blocks Na channles, increases GABA

–          Side Effects: ataxia, decreased appetite, and rash

–          Unclear how useful this med is

Ziconotide (Prialt)

–          Intrathecal only

–          Blocks N-type Ca channels in dorsal horns à prevents afferent conduction

–          Dosing: initial 2.4 picogram/day, slow titration. Max of 19.2 picograms/day

–          Side effects: hallucinations and elevated creatine kinase

–          Use for refractory pain (think pain pump patients that aren’t working)

Nimodipine (Nimotop)

–          Shown to decrease opioid dose in cancer patients

Magnesium

–          antagonist of NMDA