Pregabalin inhibits accelerated defecation and decreased colonic nociceptive threshold in sensitized rats

• Published in: European journal of pharmacology Vol. 643; no. 1; pp. 107 - 112
• Main Authors: Ohashi-Doi, Katsuyo, Gale, Jeremy D., Kurebayashi, Yoichi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.09.2010; Elsevier
• Subjects: Abdominal Pain - etiology; Abdominal Pain - physiopathology; Abdominal Pain - prevention & control; Analgesics - pharmacokinetics; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Defecation; Defecation - drug effects; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - pharmacokinetics; gamma-Aminobutyric Acid - pharmacology; gamma-Aminobutyric Acid - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Irritable bowel syndrome; Irritable Bowel Syndrome - complications; Irritable Bowel Syndrome - physiopathology; Male; Medical sciences; Neuropharmacology; Other diseases. Semiology; Pain Threshold - drug effects; Pharmacology. Drug treatments; Pregabalin; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Stress, Psychological - physiopathology; Trinitrobenzenesulfonic Acid; Visceral hypersensitivity; α 2δ calcium channel ligand; α 2δ calcium channel ligand; Pregabalin; Visceral hypersensitivity; Defecation; Irritable bowel syndrome; Nociception; Calcium; Rat; Ligand; Hypersensitivity; Rodentia; Anticonvulsant; Ionic channel; Inorganic element; α; δ calcium channel ligand; Vertebrata; Mammalia; Analgesic; Animal; Digestive diseases; Intestinal disease
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.06.014

Pregabalin, a ligand of α 2δ 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 2 h restraint stress. Oral pregabalin (10–100 mg/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 (30–100 mg/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.