Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal relea

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J Neurochem. 2005 Aug;94(4):1131-9. (NOTE: I can't remember if I

posted this before or not at all. Sorry if this is a repost.~ G)

Evidence that gabapentin reduces neuropathic pain by inhibiting the

spinal release of glutamate.

Coderre TJ, Kumar N, Lefebvre CD, Yu JS.

Departments of Anesthesia, Neurology and Neurosurgery and Psychology,

McGill University, Montreal, Canada.

Gabapentin is an anticonvulsant that successfully treats many

neuropathic pain syndromes, although the mechanism of its

antihyperalgesic action remains elusive. This study aims to help

delineate gabapentin's antihyperalgesic mechanisms. We assessed the

effectiveness of gabapentin at decreasing mechanical and cold

hypersensitivity induced in a rat model of neuropathic pain. Thus, we

compared the effectiveness of pre- or post-treatment with systemic or

intrathecal (i.t.) gabapentin at reducing the development and

maintenance of the neuropathic pain symptoms. Gabapentin successfully

decreased mechanical and cold hypersensitivity, both as a

pretreatment and post-treatment. Furthermore, both i.t. and systemic

administration of gabapentin were effective in reducing the

behavioral hypersensitivity; however, the i.t. administration was

superior to the systemic. We also examined gabapentin's effects at

inhibiting hindpaw formalin-induced release of excitatory amino acids

(EAAs) in the spinal cord dorsal horn (SCDH) both in naive rats and

in rats with neuropathic pain. We present the first evidence that

gabapentin reduces the formalin-induced release of both glutamate and

aspartate in SCDH. Furthermore, i.t. gabapentin reduces the enhanced

noxious stimulus-induced spinal release of glutamate seen in

neuropathic rats. These data suggest that gabapentin reduces

neuropathic pain symptoms by inhibiting the release of glutamate in

the SCDH.