Seltzer Ze'ev, Cohn Sergiu, Ginzburg Ruth, Beilin BenZion
Department of Physiology, Faculty of Dental Medicine, Hebrew University of Jerusalem, JerusalemIsrael Department of Anesthesiology, Hadassah University Hospital, JerusalemIsrael Department of Anesthesiology, Hasharon Hospital, Petah-TiqvaIsrael.
Pain. 1991 Apr;45(1):69-75. doi: 10.1016/0304-3959(91)90166-U.
When a peripheral nerve is severed, damaged sensory fibers emit a barrage of impulses that lasts for many seconds, or even several minutes ('injury discharge'). We have shown in rats that local anesthetic blockade of this discharge suppresses autotomy (a behavioral model of neuropathic pain). Correspondingly, mimicking prolonged injury discharge with electrical stimulation, especially of C-fibers, increased autotomy. These data support the hypothesis that injury discharge plays a role in the triggering of neuropathic pain. The mechanism of triggering autotomy was investigated using intrathecal injection of agents affecting glutamatergic transmission. A single intrathecal injection at the lumbar enlargement of the NMDA receptor blockers MK-801 and 5-APV, just prior to neurectomy, significantly suppressed autotomy. Blocking glycinergic inhibition just prior to neurectomy with a single strychnine injection strikingly enhanced autotomy. Strychnine enhancement of autotomy was prevented by prior injection of MK-801 or 5-APV. These results suggest that the expression of autotomy in rats, and by inference neuropathic pain in humans, is affected by injury discharge, possibly mediated by long-lasting, NMDA receptor-related, spinal disinhibition.
当外周神经被切断时，受损的感觉纤维会发出一连串持续数秒甚至数分钟的冲动（“损伤放电”）。我们在大鼠身上已经表明，对这种放电进行局部麻醉阻滞可抑制自残行为（一种神经性疼痛的行为模型）。相应地，用电刺激模拟长时间的损伤放电，尤其是对C纤维的刺激，会增加自残行为。这些数据支持了损伤放电在引发神经性疼痛中起作用的假说。使用鞘内注射影响谷氨酸能传递的药物来研究引发自残行为的机制。在神经切断术前，在腰椎膨大处单次鞘内注射NMDA受体阻滞剂MK-801和5-APV，可显著抑制自残行为。在神经切断术前单次注射士的宁阻断甘氨酸能抑制，会显著增强自残行为。预先注射MK-801或5-APV可防止士的宁增强自残行为。这些结果表明，大鼠自残行为的表现，以及由此推断的人类神经性疼痛，受损伤放电的影响，可能是由持久的、与NMDA受体相关的脊髓去抑制介导的。
