Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist

Irritable bowel syndrome (IBS) represents one of the most common gastrointe stinal-related diagnoses. Although the precise etiologic basis of IBS is no t known, a common presenting symptom is abdominal pain or discomfort that i s thought to develop, at least in part, from a heightened awareness of visc eral nociceptive input. Agents capable of reducing this heightened visceral nociception would, therefore, have utility in the treatment of IBS. In thi s study we evaluated the effects of intravenous and intracerebroventricular administration of a 5-HT3 receptor antagonist, alosetron, on blood pressur e changes associated with rectal distension in anesthetized and awake dogs. This vasoactive reflex serves as a model for visceral nociception. For int racerebroventricular studies, the cerebroventricular guides were placed ove r the lateral ventricle. In anesthetized studies, blood pressure was measur ed by femoral artery cannulation. In awake studies, blood pressure was moni tored by noninvasive measurement. A rectal balloon was placed in the rectum of each dog and maintained throughout the experiments. Each dose of aloset ron was given to the dogs as an intravenous or intracerebroventricular bolu s, and every 30 min the rectal balloon was inflated and blood pressure resp onses observed. In both anesthetized and awake dogs alosetron produced a si gnificant inhibition of the vasoactive reflex. In particular, alosetron sho wed high potency when administered intracerebroventricularly. Alosetron, ad ministered either centrally or peripherally, appears to modulate the viscer al nociceptive effect of rectal distension in dogs.