Central Modulation of Rectal Distension-Induced Blood Pressure Changes by Alosetron, A 5-HT3 Receptor Antagonist

Abstract

Irritable bowel syndrome (IBS) represents one ofthe most common gastrointestinal-related diagnoses.Although the precise etiologic basis of IBS is notknown, a common presenting symptom is abdominal pain or discomfort that is thought to develop, atleast in part, from a heightened awareness of visceralnociceptive input. Agents capable of reducing thisheightened visceral nociception would, therefore, have utility in the treatment of IBS. In this studywe evaluated the effects of intravenous andintracerebroventricular administration of a5-HT₃ receptor antagonist, alosetron, onblood pressure changes associated with rectal distension in anesthetized andawake dogs. This vasoactive reflex serves as a model forvisceral nociception. For intracerebroventricularstudies, the cerebroventricular guides were placed over the lateral ventricle. In anesthetized studies,blood pressure was measured by femoral arterycannulation. In awake studies, blood pressure wasmonitored by noninvasive measurement. A rectal balloonwas placed in the rectum of each dog and maintainedthroughout the experiments. Each dose of alosetron wasgiven to the dogs as an intravenous orintracerebroventricular bolus, and every 30 min therectal balloon was inflated and blood pressure responsesobserved. In both anesthetized and awake dogs alosetronproduced a significant inhibition of the vasoactivereflex. In particular, alosetron showed high potency when administered intracerebroventricularly.Alosetron, administered either centrally orperipherally, appears to modulate the visceralnociceptive effect of rectal distension indogs.