Hwang J H, Yaksh T L
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
Reg Anesth. 1997 May-Jun;22(3):249-56. doi: 10.1016/s1098-7339(06)80010-6.
Spinal gamma-aminobutyric acid (GABA) receptors have been shown to modulate post-nerve injury-induced allodynia. This study sought to examine the antiallodynic effects of a GABA analog gabapentin [1-(aminomethyl)cyclohexaneacetic acid], given by subarachnoid injection in a rat neuropathic pain model.
The rats were prepared with lumbar subarachnoid catheters, and allodynia was induced in rats by ligation of the L5-6 nerve roots (Chung model).
Spinal injection of gabapentin resulted in a dose-dependent (10-1,000 microg) antagonism of the allodynia at doses that had no detectable effect on motor function. Subarachnoid injection of either the GABA A antagonist bicuculline (0.3 microg), or the GABA B antagonist CGP 35348 (30 microg) 5 minutes before or 60 minutes after injection of GABA receptor agonist did not reverse the antiallodynic effects produced by gabapentin.
Gabapentin shows antiallodynic effect, but its mechanism is not known. The failure to reverse this effect by GABA A or B antagonists at doses that reverse the effects of the respective agonists suggests that gabapentin is involved in the modulation of spinal systems by mechanisms that do not involve either a GABA A or a GABA B site.
脊髓γ-氨基丁酸(GABA)受体已被证实可调节神经损伤后诱导的痛觉过敏。本研究旨在通过蛛网膜下腔注射给予GABA类似物加巴喷丁[1-(氨甲基)环己烷乙酸],在大鼠神经性疼痛模型中检测其抗痛觉过敏作用。
给大鼠植入腰段蛛网膜下腔导管,通过结扎L5-6神经根(Chung模型)诱导大鼠产生痛觉过敏。
脊髓注射加巴喷丁对痛觉过敏产生剂量依赖性(10-1000微克)拮抗作用,且这些剂量对运动功能无明显影响。在注射GABA受体激动剂前5分钟或后60分钟蛛网膜下腔注射GABA A拮抗剂荷包牡丹碱(0.3微克)或GABA B拮抗剂CGP 35348(30微克),均不能逆转加巴喷丁产生的抗痛觉过敏作用。
加巴喷丁具有抗痛觉过敏作用,但其机制尚不清楚。在能逆转各自激动剂作用的剂量下,GABA A或B拮抗剂未能逆转加巴喷丁的这一作用,提示加巴喷丁通过不涉及GABA A或GABA B位点的机制参与脊髓系统的调节。