Faculty Collaboration Database

Effects of the 5-HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia. Pain 2006 Dec 15;126(1-3):54-63

Date

07/18/2006

Pubmed ID

16844296

DOI

10.1016/j.pain.2006.06.014

Scopus ID

2-s2.0-33751009935 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

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.

Author List

Miranda A, Peles S, McLean PG, Sengupta JN

Authors

Adrian Miranda MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Absorption
Animals
Carbolines
Colon
Dilatation, Pathologic
Electromyography
Gastrointestinal Motility
Hyperalgesia
Injections, Intramuscular
Injections, Spinal
Male
Pain Measurement
Rats
Rats, Sprague-Dawley
Rectum
Serotonin 5-HT3 Receptor Antagonists
Serotonin Antagonists
Viscera