Gabapentin (1–[aminomethyl] cyclohexane-acetic acid) is an antiepileptic drug which was introduced in 1993 and was originally approved for the treatment of partial seizures with or without secondary generalisation. Recently, however, reports have documented its efficacy in the treatment of various neuropathic pain states, such as complex regional pain syndrome, deafferentation neuropathy of the face, post-herpetic neuralgia, sciatic-type pain and HIV-related neuropathy.
The adult dose for neuropathic pain is 300 mg on day 1, then 300 mg twice daily on day 2, then 300 mg 8 hourly on day 3, increasing according to response in steps of 300 mg daily (8 hourly) up to a maximum of 1.8 g daily [i]. Gabapentin is reportedly completely ineffective in altering threshold responses to acute nociceptive stimuli at doses up to 300 mg/kg. Presently, the mechanism of action as either an anticonvulsant or an analgesic is unknown. The antinociceptive effects are likely to be due to actions within the spinal cord, because 1000 times the IT dose is required to produce equianalgesic effects when given intraperitoneally. Gabapentin binds to the alpha- 2-delta calcium channel subunit. However, the relationship between binding at this site and the analgesic properties of gabapentin have not been determined. The NMDA receptor complex may be a potential spinal locus for neuropathic pain relief, but it has not been conclusively found that this is the major site of action. Gabapentin has a relatively benign side-effect profile and is well tolerated if dosing proceeds in a gradually escalating manner. It has few, if any, drug interactions and is primarily renally excreted. Although expensive, it does not require the routine monitoring of blood chemistry and liver functions tests, as is the case with carbamazepine and phenytoin.
Pregabalin is a more recently developed drug (similar to gabapentin) licensed for neuropathic pain. Its efficacy and side-effect profile is similar to gabapentin but it is easier to titrate.
[i] British National Formulary (BNF54); September 2007
[ii] Gabapentin for acute and chronic pain.
Wiffen P, McQuay H, Edwards J, Moore R.
Cochrane Database Syst Rev. 2005 Jul 20;(3)