Gabapentin use in neuropathic pain syndromes

The development of neuropathic pain involves a series of changes including primary and secondary hyperalgesia, peripheral and central sensitization, and wind-up phenomena. Neurotransmitters play a critical role in this process. For example, glutaminergic subtypes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and neurokinin prime the N-methyl-D-aspartate (NMDA) receptor by triggering the release of intracellular calcium ions, thus unblocking the magnesium ion plug on the NMDA receptor and allowing Ca2+ influx into the cell. Ca2+ ions acting as secondary messengers initiate protein kinase C activation, phospholipase C and nitric oxide synthetase production, and proto-oncogene expression. The activation of the NMDA receptor thereby increases the responsiveness of the nociceptive system. Anticonvulsant drugs--including carbamazepine, phenytoin, and felbamate--have been used to treat neuropathic pain. Gabapentin is a novel anticonvulsant that may have a unique effect on voltage-dependent Ca2+ channel currents at postsynaptic dorsal horn neurons. Thus, gabapentin may interrupt an entire series of events, not just a single process, that lead to the development of neuropathic pain. Preclinical models of anti-inflammatory and neuropathic pain indicate that gabapentin effectively antagonizes the maintenance of this pain. Additionally, in preemptive surgical models, gabapentin has been shown to prevent the induction of pain. Gabapentin has been shown to be efficacious in numerous smaller clinical studies, case reports, and chart reviews in a variety of neuropathic pain syndromes. Two large multicenter studies, one in postherpetic neuralgia (PHN) and one in diabetic peripheral neuropathy (DPN), support preclinical findings. In the PHN study, patients treated with gabapentin demonstrated a significant difference (P<0.001) in their average daily pain score at endpoint compared to placebo patients. In the DPN trial, mean weekly pain was significantly (P<0.001) different for gabapentin-treated patients compared to placebo-treated patients at endpoint. Consistent with the known side-effect profile of gabapentin, the most common adverse events noted in both studies were dizziness and somnolence. Gabapentin should be considered an important addition to the management of neuropathic pain syndromes.