Yoon Myung Ha, Choi Jeong Il, Jeong Seong Wook
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea.
J Korean Med Sci. 2003 Apr;18(2):255-61. doi: 10.3346/jkms.2003.18.2.255.
Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.
已知脊髓注射加巴喷丁具有抗伤害感受作用。尽管已经提出了几种假设，但加巴喷丁的作用机制尚未明确确立。本研究旨在探讨加巴喷丁在脊髓水平的作用机制。选用雄性SD大鼠进行鞘内导管植入。在福尔马林试验中评估加巴喷丁的效果。在用多种类别的药物预处理后，检测加巴喷丁效果的变化。同时也观察一般行为。鞘内注射加巴喷丁可抑制福尔马林试验中的第2期退缩反应，但对第1期无效。鞘内注射NMDA、AMPA、D-丝氨酸、CGS 15943、阿托品和纳洛酮可逆转鞘内注射加巴喷丁的抗伤害感受作用。给予荷包牡丹碱、氯苯氨丁酸、哌唑嗪、育亨宾、美加明、L-亮氨酸、双氢麦角隐亭或毒胡萝卜素后未见拮抗作用。综上所述，鞘内注射加巴喷丁仅减弱了易化状态。在脊髓水平，NMDA受体、AMPA受体、NMDA受体的非士的宁位点、腺苷受体、毒蕈碱受体和阿片受体可能参与加巴喷丁的抗伤害感受作用，而GABA受体、L-氨基酸转运体、肾上腺素能受体、烟碱受体、5-羟色胺受体或钙可能不参与。
