Department of Anesthesiology and Intensive Care, University Hospital Münster, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany.
Pain. 2012 Jan;153(1):129-141. doi: 10.1016/j.pain.2011.09.028. Epub 2011 Nov 3.
Impairment of spinal GABAergic inhibition is demonstrated to contribute to pathologic chronic pain states. We investigated spinal and peripheral GABAergic regulation of incisional pain in rats. We found that intrathecal but not peripheral administration of muscimol (GABA-A receptor agonist) and baclofen (GABA-B receptor agonist) reduced mechanical and thermal hyperalgesia after plantar incision in rats. Nonevoked pain behavior after incision was unaffected by these agonists. Similarly, nociception in unincised rats was not reduced by the same dose of agonists. Thus, GABA-A and GABA-B receptors are involved in mediating incision-induced hyperalgesia (but not nonevoked pain). Intrathecal and systemic application of L-838,417, a subtype-selective benzodiazepine site agonist (α2, α3, α5), reduced mechanical and heat hyperalgesia after incision, indicating a role of these subunits in mediating incision-induced hyperalgesia. Interestingly, the effects of all agonists were more intense and prolonged on the day after surgery than on the day of incision. Similarly, spinally administered GABA-A and GABA-B antagonists increased pain behavior, again with a greater effect 1 day after incision. One possible explanation for this finding might be that an incision modulates GABA-mediated inhibition 1 day after incision. However, expression of GABA-A receptor subunits α2 and α3 and GABA-B receptor subunits within the dorsal horn of the spinal cord were unchanged after incision, indicating that receptor expression cannot explain a possible modulation of GABAergic inhibition after incision. Thus, other mechanisms need to be considered. In conclusion, GABA-A and GABA-B receptors are promising targets for postoperative, incisional pain in humans.
脊髓 GABA 能抑制的损伤被证明有助于病理性慢性疼痛状态。我们研究了脊髓和外周 GABA 对大鼠切口疼痛的调节。我们发现，鞘内而不是外周给予 muscimol（GABA-A 受体激动剂）和 baclofen（GABA-B 受体激动剂）可减轻大鼠足底切口后的机械性和热痛觉过敏。这些激动剂对切口后无诱发的疼痛行为没有影响。同样，相同剂量的激动剂也不会减轻未切口大鼠的痛觉。因此，GABA-A 和 GABA-B 受体参与介导切口引起的痛觉过敏（而不是无诱发的疼痛）。鞘内和全身应用 L-838,417，一种亚型选择性苯二氮䓬位点激动剂（α2、α3、α5），可减轻切口后的机械性和热痛觉过敏，表明这些亚基在介导切口引起的痛觉过敏中起作用。有趣的是，与手术当天相比，所有激动剂在手术后的第一天的效果更强且持续时间更长。同样，鞘内给予 GABA-A 和 GABA-B 拮抗剂增加了疼痛行为，在切口后 1 天的效果更大。这一发现的一个可能解释是切口在切口后 1 天调节 GABA 介导的抑制。然而，GABA-A 受体亚基 α2 和 α3 和 GABA-B 受体亚基在脊髓背角中的表达在切口后没有改变，表明受体表达不能解释切口后 GABA 能抑制的可能调节。因此，需要考虑其他机制。总之，GABA-A 和 GABA-B 受体是人类术后切口疼痛的有希望的靶点。
