Patterns of serotonin- and 2-methylserotonin-induced pain may reflect 5-HT3 receptor sensitization.
Intraperitoneal injection of serotonin (5-HT; 0.5-4.0 mg/kg) produced dose-dependent nociceptive writhing responses, attenuated at all doses by pre-administration of tropisetron (1.0 mg/kg, i.p.). Administration of 2-methylserotonin (2-methyl-5-HT) alone was ineffective in inducing writhing. The effects of 5-HT (0.5 mg/kg, i.p.) were increased by subsequent injection of 2-methyl-5-HT (0.5-4.0 mg/kg, i.p.). The enhanced nociceptive responses produced by low dose of 5-HT and subsequently administered 2-methyl-5-HT were attenuated by pretreatment with tropisetron. These results suggest that the inflammatory cascade produced by peripheral administration of 5-HT evokes nociception by stimulating visceral 5-HT(3) receptors and that 5-HT-induced mechanisms appear to sensitize the 5-HT(3) receptor to subsequent pharmacologic activation.
Giordano
James
J
Department of Pathology, Research Institute, Moody Health Sciences Center/TCC, Pasadena, TX 77505, USA. Gsynapse22@aol.com
Gerstmann
Hannah
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077526:Tropisetron
D007211:Indoles; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012701:Serotonin; D000077526:Tropisetron; C045918:2-methyl-5-HT