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 gastrointestinal-related diagnoses. Although the precise etiologic basis of IBS is not known, a common presenting symptom is abdominal pain or discomfort that is thought to develop, at least in part, from a heightened awareness of visceral nociceptive input. Agents capable of reducing this heightened visceral nociception would, therefore, have utility in the treatment of IBS. In this study we evaluated the effects of intravenous and intracerebroventricular administration of a 5-HT3 receptor antagonist, alosetron, on blood pressure changes associated with rectal distension in anesthetized and awake dogs. This vasoactive reflex serves as a model for visceral nociception. For intracerebroventricular studies, the cerebroventricular guides were placed over the lateral ventricle. In anesthetized studies, blood pressure was measured by femoral artery cannulation. In awake studies, blood pressure was monitored by noninvasive measurement. A rectal balloon was placed in the rectum of each dog and maintained throughout the experiments. Each dose of alosetron was given to the dogs as an intravenous or intracerebroventricular bolus, and every 30 min the rectal balloon was inflated and blood pressure responses observed. In both anesthetized and awake dogs alosetron produced a significant inhibition of the vasoactive reflex. In particular, alosetron showed high potency when administered intracerebroventricularly. Alosetron, administered either centrally or peripherally, appears to modulate the visceral nociceptive effect of rectal distension in dogs.