Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat.
In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(+)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 +/- 1.27 versus 43.4 +/- 1.98 mm Hg). Pregabalin (30-200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.
Department of Pharmacology, Pfizer Global Research, Fresnes Laboratories 3-9, rue de la Loge, BP-100 Fresnes Cedex, France. laurent.diop@pfizer.com
Laurent
L
Diop
Frederic
F
Raymond
Helene
H
Fargeau
Francine
F
Petoux
Maria
M
Chovet
Annette M
AM
Doherty
D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D002908:Chronic Disease; D003106:Colon / Q000473:pathology; D003108:Colonic Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D006940:Hyperemia / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D009195:Peroxidase / Q000378:metabolism; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000701:Analgesics, Opioid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase