Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate
Article first published online: 5 JUL 2005
Journal of Neurochemistry
Volume 94, Issue 4, pages 1131–1139, August 2005
How to Cite
Coderre, T. J., Kumar, N., Lefebvre, C. D. and Yu, J. S. C. (2005), Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 94: 1131–1139. doi: 10.1111/j.1471-4159.2005.03263.x
- Issue published online: 5 JUL 2005
- Article first published online: 5 JUL 2005
- Received February 15, 2005; revised manuscript received April 13 2005; accepted April 20, 2005.
- chronic constriction injury;
- in vivo microdialysis;
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 naïve 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.