Cheng J K, Pan H L, Eisenach J C
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Anesthesiology. 2000 Apr;92(4):1126-31. doi: 10.1097/00000542-200004000-00031.
Systemic administration of gabapentin was shown previously to attenuate mechanical allodynia in a rat model of postoperative pain. Because intrathecal administration of gabapentin is effective in other hypersensitivity states, the authors tested its effect in the postoperative model, its interaction with another antiallodynic agent (clonidine), and a possible mechanism of gabapentin action (entry into sites of action via an L-amino acid transporter).
Male Sprague-Dawley rats were anesthetized with halothane, and an incision of the plantaris muscle of right hind paw induced punctate mechanical allodynia. Withdrawal threshold to von Frey filament application near the incision site was determined before and 2 h after surgery. Then, an intrathecal injection was performed and thresholds were determined every 30 min for 3 h thereafter.
Paw incision induced a mechanical hypersensitivity (mechanical threshold > 25 g before incision and < 5 g after). Intrathecal gabapentin dose-dependently (10-100 microg) reduced mechanical allodynia. Intrathecal injection of an inhibitor of L-amino acid transporters or a competitor for this transporter, L-leucine, did not reverse the intrathecal effect of gabapentin. The ED50 of intrathecal gabapentin, clonidine, and their combination were 51, 31, and 9 microg, respectively, and isobolographic analysis showed synergy between gabapentin and clonidine.
Intrathecal gabapentin is effective against tactile allodynia that occurs after paw incision, and interacts synergistically with clonidine. Unlike results in vitro, gabapentin does not obligatorily need to enter cells via the L-amino acid transporter mechanism to achieve its effects in vivo.
先前的研究表明，在大鼠术后疼痛模型中，全身性给予加巴喷丁可减轻机械性异常性疼痛。由于鞘内注射加巴喷丁在其他超敏反应状态下有效，因此作者测试了其在术后模型中的作用、与另一种抗异常性疼痛药物（可乐定）的相互作用以及加巴喷丁作用的可能机制（通过L-氨基酸转运体进入作用位点）。
雄性Sprague-Dawley大鼠用氟烷麻醉，右后爪跖肌切开诱导点状机械性异常性疼痛。在手术前和手术后2小时测定切口部位附近对von Frey细丝施加的撤针阈值。然后进行鞘内注射，此后每30分钟测定一次阈值，共3小时。
爪部切开诱导了机械性超敏反应（切开前机械阈值>25 g，切开后<5 g）。鞘内注射加巴喷丁（10 - 100微克）剂量依赖性地减轻了机械性异常性疼痛。鞘内注射L-氨基酸转运体抑制剂或该转运体的竞争性抑制剂L-亮氨酸，并未逆转加巴喷丁的鞘内作用。鞘内注射加巴喷丁、可乐定及其组合的半数有效剂量（ED50）分别为51、31和9微克，等效应线图分析显示加巴喷丁和可乐定之间存在协同作用。
鞘内注射加巴喷丁对爪部切开后出现的触觉异常性疼痛有效，并与可乐定协同作用。与体外结果不同，加巴喷丁在体内发挥作用不一定需要通过L-氨基酸转运体机制进入细胞。
