Carlton S M, Zhou S
Department of Anatomy and Neuroscience, Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-1069, USA.
Pain. 1998 May;76(1-2):201-7. doi: 10.1016/s0304-3959(98)00043-8.
Gabapentin (GP) has been shown to have antihyperalgesic properties and the site of drug action is reported to be the central nervous system. The goal of the present study was to determine whether GP also has a peripheral site of action. Rats received intraplantar 20-microl injections of 6, 60 or 600 microg GP + 2% formalin, 300 or 600 microg S-(+)-3-isobutylgaba + 2% formalin, 600 microg R-(-)-3-isobutylgaba + 2% formalin or formalin alone. The two lower doses of GP significantly reduced flinching and lifting/licking behavior during phase 2; however, phase 1 behaviors were unaffected, 600 microg GP significantly reduced these nociceptive behaviors during both phases. 600 microg S-(+)-3-isobutylgaba also reduced formalin-induced nociceptive behaviors; however, 600 microg of the isomer R-(-)-3-isobutylgaba had no effect. The antihyperalgesic effect of GP (1) was not due to a systemic effect since animals injected with 600 microg GP in one hindpaw and 2% formalin into the contralateral hindpaw developed nociceptive behaviors which were no different than those seen in animals injected with formalin alone; (2) was not due to a local anesthetic effect since needle sticks within the drug-injected region evoked paw withdrawal behavior which was not different from pre-drug levels; (3) was blocked by 20 microl D-serine but not by L-serine. Although the mechanism of action of GP has yet to be elucidated, these results indicate that GP has a peripheral site of action and thus may offer a novel therapeutic agent for topical or local treatment of pain of peripheral origin.
加巴喷丁（GP）已被证明具有抗痛觉过敏特性，据报道其药物作用部位是中枢神经系统。本研究的目的是确定GP是否也具有外周作用部位。给大鼠足底注射20微升6、60或600微克的GP + 2%福尔马林、300或600微克的S-(+)-3-异丁基氨基丁酸 + 2%福尔马林、600微克的R-(-)-3-异丁基氨基丁酸 + 2%福尔马林或仅注射福尔马林。较低剂量的两种GP在第2阶段显著减少了退缩和抬起/舔舐行为；然而，第1阶段的行为未受影响，600微克的GP在两个阶段均显著减少了这些伤害性感受行为。600微克的S-(+)-3-异丁基氨基丁酸也减少了福尔马林诱导的伤害性感受行为；然而，600微克的异构体R-(-)-3-异丁基氨基丁酸没有效果。GP（(1)）的抗痛觉过敏作用不是由于全身作用，因为在一只后爪注射600微克GP而在对侧后爪注射2%福尔马林的动物出现的伤害性感受行为与仅注射福尔马林的动物没有差异；(2)）不是由于局部麻醉作用，因为在注射药物区域内的针刺引起的爪退缩行为与给药前水平没有差异；(3)）被20微升的D-丝氨酸阻断，但未被L-丝氨酸阻断。尽管GP的作用机制尚未阐明，但这些结果表明GP具有外周作用部位，因此可能为外周源性疼痛的局部或局部治疗提供一种新型治疗药物。
