EVALUATION OF GABAPENTIN AND S-(-3-ISOBUTYLGABA IN A RAT MODEL OF POSTOPERATIVE PAIN())

Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant agents that sel ectively interact with the alpha(2) delta subunit of voltage-dependent calcium channels. This report describes the activities of these two c ompounds in a rat model of postoperative pain. An incision of the plan taris muscle of a hind paw induced thermal hyperalgesia and tactile al lodynia lasting at least 3 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia and von Frey hairs fo r tactile allodynia. A single s.c. dose of gabapentin, 1 h before surg ery, dose-dependently (3-30 mg/kg) blocked the development of allodyni a and hyperalgesia with a minimum effective dose (MED) of 10 and 30 mg /kg, respectively. The highest dose of gabapentin prevented developmen t of hyperalgesia and allodynia for 24 and 49 h, respectively. Similar administration of S-(+)-3-isobutylgaba also dose-dependently (3-30 mg /kg, s.c.) prevented development of hyperalgesia and allodynia with ME D of 3 and 10 mg/kg, respectively. The highest dose of S-(+)-3-isobuty lgaba completely blocked development of both nociceptive responses for 3 days. The administration of S-(+)3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery also completely blocked the maintenance of hyperalgesia and allodynia, but its duration of action was much shorter (3 h). The administration of morphine (1-6 mg/kg s.c.) 0.5 h before surgery prev ented the development of thermal hyperalgesia with a MED of 1 mg/kg. H owever, unlike gabapentin and S-(+)-3-isobutylgaba, it had little effe ct on the development of tactile allodynia. It is suggested that gabap entin and S-(+)-3-isobutylgaba may be effective in the treatment of po stoperative pain.