Effects of the 5-HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia

• Published in: Pain (Amsterdam) Vol. 126; no. 1; pp. 54 - 63
• Main Authors: Miranda, Adrian, Peles, Shachar, McLean, Peter G., Sengupta, Jyoti N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.12.2006; Elsevier
• Subjects: 5-HT3 Receptor; Absorption; Alosetron; Animals; Biological and medical sciences; Carbolines - administration & dosage; Carbolines - pharmacokinetics; Carbolines - pharmacology; Colon - physiopathology; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Dilatation, Pathologic; Electromyography; Gastrointestinal Motility - drug effects; Hyperalgesia - physiopathology; Injections, Intramuscular; Injections, Spinal; Male; Medical sciences; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Pain Measurement; Rats; Rats, Sprague-Dawley; Rectum - physiopathology; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - pharmacokinetics; Serotonin Antagonists - pharmacology; Somatic pain; Viscera; Visceral hyperalgesia; 5-HT3 Receptor; Somatic pain; Serotonin; Alosetron; Visceral hyperalgesia; Animal model; Rat; Hypersensitivity; Rodentia; Hyperalgesia; Vertebrata; Mammalia; Pain; Neurotransmitter; pH; Gastrocnemius muscle; Biological receptor
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2006.06.014

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 μl) 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 μg/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.