Pregabalin inhibits accelerated defecation and decreased colonic nociceptive threshold in sensitized rats
| Autor: | Yoichi Kurebayashi, Katsuyo Ohashi-Doi, Jeremy D. Gale |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Pain Threshold Restraint Physical medicine.medical_specialty Analgesic Pregabalin Distension Irritable Bowel Syndrome Rats Sprague-Dawley Internal medicine Animals Medicine Defecation gamma-Aminobutyric Acid Irritable bowel syndrome Pharmacology Analgesics Dose-Response Relationship Drug Voltage-dependent calcium channel business.industry medicine.disease digestive system diseases Abdominal Pain Rats Dose–response relationship Nociception Endocrinology Trinitrobenzenesulfonic Acid Anesthesia business Stress Psychological medicine.drug |
| Zdroj: | European Journal of Pharmacology. 643:107-112 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2010.06.014 |
| Popis: | Pregabalin, a ligand of alpha(2)delta subunits of voltage-gated calcium channels, reduces visceral hypersensitivity associated with irritable bowel syndrome. However, effects of pregabalin on bowel function are not well described. We investigated the effects of pregabalin on bowel dysfunction and colonic nociceptive threshold in sensitized rats. Increased fecal pellet output was evoked by non-ulcerogenic stress. Decreased colonic nociceptive threshold was induced in separate rats by administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the lumen of the proximal colon. Fecal pellet output was significantly increased during 2h restraint stress. Oral pregabalin (10-100mg/kg, p.o.) inhibited this increased fecal output dose-dependently, but did not change fecal output in naïve rats. The response threshold to distension of the non-inflamed distal colon was significantly decreased seven days after TNBS administration. An anti-hyperalgesic effect of pregabalin (30-100mg/kg, p.o.) that opposed the decreased colonic nociceptive threshold in TNBS-sensitized rats was observed, but nociceptive thresholds were not changed in naïve rats. Moreover, pregabalin was more potent in reducing disturbed defecation compared with reduction in nociceptive threshold to distension in TNBS-sensitized rats. This is the first report that pregabalin modulates stress-induced defecation in rats. These data indicate that pregabalin can ameliorate both altered defecation and decreases in colonic nociceptive threshold, suggesting that pregabalin might warrant investigation for the treatment of irritable bowel syndrome. |
| Databáze: | OpenAIRE |
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