PENTOBARBITAL, DIAZEPAM, AND ETHANOL ABOLISH THE INTERPHASE DIMINUTION OF PAIN IN THE FORMALIN TEST - EVIDENCE FOR PAIN MODULATION BY GABA(A) RECEPTORS

There are two phases to the behavioral response to injection of formal in. After an initial vigourous response, a period of reduced pain occu rs 10 to 15 n-tin after formalin, followed by reemergence of pain-rela ted behaviors. These phases are believed to represent acute chemical s timulation of afferent neurons followed by injury-related inflammatory pain. Pentobarbital (10, 15, or 25 mg/kg), diazepam (0.5, 1.5, or 5.0 mg/kg), or ethanol (0.5, 1.0, or 1.5 g/kg) attenuated the diminution of pain between the two phases, so that pain was continuous throughout 60 min of testing, but had no effect on pain scores during the peaks of either phase. The effects of pentobarbital and diazepam were blocke d by picrotoxin (2.5 mg/kg), which itself had no effect. Ro 15-1788 al so blocked the effect of diazepam. Picrotoxin did not effectively anta gonize the effect of ethanol. A high dose of picrotoxin (5.0 mg/kg) ca used seizures in some rats and also eliminated the interphase depressi on of pain. The results suggest that the biphasic time course of forma lin pain is produced by a central antinociceptive mechanism that is in hibited by GABA(A) receptors.