Analgesic profile of centrally administered 2-methylserotonin against acute pain in rats.
The present study examined patterns of analgesia by intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of the serotonin 5-HT3 receptor agonist, 2-methylserotonin (1-100 micrograms) 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 micrograms doses. In contrast, only the 100 micrograms 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 micrograms) in the formalin test were attenuated by pretreatment (10 micrograms 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 micrograms 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.
Giordano
J
J
Neuropharmacology Laboratory, College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311.
D000700:Analgesics; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000378:metabolism / Q000494:pharmacology
D000700:Analgesics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D008803:Mianserin; D012701:Serotonin; D009270:Naloxone; C045918:2-methyl-5-HT; D007650:Ketanserin; C042253:bemesetron; D001640:Bicuculline