Effects of the 5-HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia.
Conflicting results exist regarding the role of 5-HT3 receptors in somatic and visceral nociceptive processing. We aimed to investigate the effects of the 5-HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia. Two injections (100 microl) of either pH 4.0 or 7.2 saline were given unilaterally in the gastrocnemius (GN) muscle. In all groups, the paw withdrawal thresholds (PWT) to von Frey filaments and the visceromotor responses (VMR) to colorectal distension (CRD) were recorded before the saline injections and 72 h, and 1 week after the second injection. Intrathecal (i.t.) (25 nmol) or intravenous (i.v.) (100 microg/kg/day) alosetron was given daily following the second injection and compared to either i.v. or i.t. saline (vehicle). There was a significant decrease in the mean PWT bilaterally in all groups following pH 4.0 injections (p<0.05). Intravenous alosetron resulted in a significant increase in the PWT bilaterally on days 2 and 3. Intrathecal alosetron resulted in significant increase in the PWT starting at day 3 and was significantly higher than baseline on days 4-7 (p<0.05). At CRD pressures 30 mmHg, the VMR of pH 4.0 injected rats was significantly increased at 72 h and 1 week (p<0.05). Both i.v. and i.t. alosetron treated rats failed to demonstrate any alteration in the VMR. Control rats (pH 7.2) failed to show any alteration in the VMR and were unaffected by alosetron. Both, systemically and centrally administered alosetron, reversed the mechanical somatic hypersensitivity and prevented the development of visceral hyperalgesia, suggesting a centrally mediated effect.
Miranda
Adrian
A
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. amiranda@mail.mcw.edu
Peles
Shachar
S
McLean
Peter G
PG
Sengupta
Jyoti N
JN
D000042:Absorption; D000818:Animals; D002243:Carbolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003106:Colon / Q000503:physiopathology; D004108:Dilatation, Pathologic; D004576:Electromyography; D005769:Gastrointestinal Motility / Q000187:drug effects; D006930:Hyperalgesia / Q000503:physiopathology*; D007273:Injections, Intramuscular; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000503:physiopathology; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014781:Viscera
D002243:Carbolines; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; C090840:alosetron