ANALGESIC PROFILE OF CENTRALLY ADMINISTERED 2-METHYLSEROTONIN AGAINST ACUTE PAIN IN RATS

The present study examined patterns of analgesia produced by intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of the serotonin 5-HT3 receptor agonist, 2-methylserotonin (1-100-mu-g) against acute thermal, mechanical or formalin-induced chemo-inflammatory pain in male rats. Neither i.c.v. or i.t. 2-methylserotonin produced motoric, sedative or respiratory effects. I.c.v. 2-methylserotonin was not analgesic at any dose in the pain assays employed. I.t. 2-methylserotonin produced dose-related analgesia in the formalin test with significant effects at 20-100-mu-g doses. In contrast, only the 100-mu-g dose of 2-methylserotonin produced analgesia against thermal pain, and analgesia was not observed at any dose in the mechanical pain test. The effects of 2-methylserotonin (100-mu-g) in the formalin test were attenuated by pretreatment (10-mu-g i.t.) with the 5-HT3 receptor antagonist MDL-72222, opioid antagonist naloxone or GABA antagonist bicuculline; the 5-HT2-receptor antagonist ketanserin or 5-HT1 receptor antagonist mianserin did not affect 2-methylserotonin-induced analgesia. In the thermal test, i.t. pretreatment with MDL-72222, ketanserin, naloxone or bicuculline, but not mianserin, reduced analgesic effects of 2-methylserotonin (100-mu-g i.t.). These findings suggest that spinal 5-HT3, opioid and GABA receptor systems interact to mediate acute chemo-inflammatory pain, and implicate the interaction of these systems with 5-HT2 receptor substrates in analgesia against acute thermal nociception.