Coderre Terence J, Kumar Naresh, Lefebvre Celeste D, Yu Jonathan S C
Departments of Anesthesia, Neurology and Neurosurgery and Psychology, McGill University, Montreal, Canada.
J Neurochem. 2005 Aug;94(4):1131-9. doi: 10.1111/j.1471-4159.2005.03263.x.
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.
加巴喷丁是一种抗惊厥药，可成功治疗多种神经性疼痛综合征，但其抗痛觉过敏作用的机制仍不清楚。本研究旨在帮助阐明加巴喷丁的抗痛觉过敏机制。我们评估了加巴喷丁在减轻神经性疼痛大鼠模型中诱导的机械性和冷超敏反应方面的有效性。因此，我们比较了全身或鞘内注射（i.t.）加巴喷丁预处理或后处理在减轻神经性疼痛症状的发展和维持方面的有效性。加巴喷丁作为预处理和后处理均成功降低了机械性和冷超敏反应。此外，鞘内注射和全身给药加巴喷丁均能有效降低行为超敏反应；然而，鞘内注射优于全身给药。我们还研究了加巴喷丁在未处理大鼠和神经性疼痛大鼠中抑制后爪福尔马林诱导的脊髓背角（SCDH）兴奋性氨基酸（EAA）释放的作用。我们首次证明加巴喷丁可减少SCDH中福尔马林诱导的谷氨酸和天冬氨酸的释放。此外，鞘内注射加巴喷丁可减少神经性大鼠中有害刺激诱导的脊髓谷氨酸释放增强。这些数据表明，加巴喷丁通过抑制SCDH中谷氨酸的释放来减轻神经性疼痛症状。
