期刊
NEUROPHARMACOLOGY
卷 46, 期 5, 页码 743-749出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2003.11.010
关键词
gabapentin; synaptic transmission; spinal cord; dorsal horn; calcium channel; pain
Gabapentin is a lipophilic analog of gamma-amino butyric acid (GABA) with therapeutic activity against certain forms of epilepsy and neuropathic pain. Despite its structural similarity to GABA, it does not bind GABA(A) or GABA(B) receptors and the mechanism, especially of its analgesic action, has remained elusive. Here. we have Studied its effects on synaptic transmission mediated by the major spinal fast excitatory and inhibitory neurotransmitters, L-glutamate and glycine, in the superficial layers of the spinal cord dorsal horn, a CNS area, which is critically involved in nociception. Gabapentin reversibly reduced evoked excitatory postsynaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxizolepropionate (AMPA-EPSCs) and inhibitory postsynaptic currents mediated by glycine (gly-IPSCs). Inhibition of AMPA-EPSCs and gly-IPSCs occurred with similar potencies (similar to10-50, currents mediated by glycine (gly-IPSCs). Gabapentin did not affect membrane Currents elicited by exogenously nM) and by about the same degree applied glutamate or glycine arguing against a postsynaptic site of action. Selective blockade of N-type Ca2+ channels with omega-conotoxin GVIA dramatically increased and blockade of P/Q-type channels with omega-agatoxin IVA strongly attenuated inhibition of evoked synaptic transmission by gabapentin. These results show that gabapentin affects both excitatory and inhibitory spinal neurotransmission via a presynaptic mechanism which preferentially involves P/Q-type Ca2+ channels. (C) 2004 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据