THE NMDA ANTAGONIST MEMANTINE BLOCKS PAIN BEHAVIOR IN A RAT MODEL OF FORMALIN-INDUCED FACIAL-PAIN

Recent studies have provided evidence that excitatory amino acid antag onists can exert analgesic effects in animals. These studies, however, have focused primarily on phasic pain or hyperalgesia rather than ton ic pain. The present study evaluates the effects of systemic administr ation of Memantine (1-amino-3,5-dimethyl-adamantane), a clinically use d N-methyl-D-aspartate (NMDA) receptor antagonist, on formalin-induced phasic and tonic pain behavior in the rat. Memantine (2.5, 5.0, 10.0 and 20.0 mg/kg) or normal saline was injected i.p. 1 h prior to a s.c. injection of formalin (5%, 50 mul) into the vibrissal pad of adult ra ts (n = 5/group). Pain behavior was measured by the number of seconds of formalin-induced face grooming during a 42-min post-injection obser vation period. Saline-injected animals displayed a biphasic face-groom ing response, consisting of an early, phasic phase (0-6 min) and a del ayed, prolonged tonic phase (12-42 min). Memantine at doses of 2.5-10 mg/kg produced a significant dose-related inhibition of the second pha se (65-93%) and a much smaller inhibition of the first phase (up to 52 %). A higher dose (20 mg/kg) further inhibited both phases but also pr oduced other motor effects (increased exploratory and decreased freezi ng behavior, hind-paw weakness and gait ataxia) which were not observe d at the lower doses. These results suggest that the NMDA receptor ant agonist Memantine can block formalin-induced tonic and, to a lesser ex tent, phasic pain, at doses that do not alter other observed motor beh aviors.