ATTENUATION OF FORMALIN-INDUCED NOCICEPTIVE BEHAVIORS FOLLOWING LOCALPERIPHERAL INJECTION OF GABAPENTIN

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-mu l injectio ns of 6, 60 or 600 mu g GP + 2% formalin, 300 or 630 mu g S-(+)-3-isob utylgaba + 2% formalin, 600 mu g R-(-)-3-isobutylgaba + 2% formalin or formalin alone. The two lower doses of GP significantly reduced flinc hing and lifting/licking behavior during phase 2; however, phase 1 beh aviors were unaffected, 600 mu g GP significantly reduced these nocice ptive behaviors during both phases. 600 mu g S-(+)-3-isobutylgaba also reduced formalin-induced nociceptive behaviors; however, 600 mu g of the isomer R-(-)-3-isobutylgaba had no effect. The antihyperalgesic ef fect of GP (1) was not due to a systemic effect since animals injected with 600 mu g GP in one hindpaw and 2% formalin into the contralatera l hindpaw developed nociceptive behaviors which were no different than those seen in animals injected with formalin alone; (2) was not due t o a local anesthetic effect since needle sticks within the drug-inject ed region evoked paw withdrawal behavior which was not different from pre-drug levels; (3) was blocked by 20 mu l D-serine but not by L-seri ne. Although the mechanism of action of GP has yet to be elucidated, t hese 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. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.