Effect of zaldaride maleate, an antidiarrheal compound, on visceral pain reflex induced by small intestinal distention in anesthetized rats

Using distention of the small intestine as a visceral pain model, we invest igated the effect of zaldaride maleate (ZAL), a selective inhibitor of calm odulin, on the depressor response. In pentobarbital-anesthetized rats, smal l intestine distention was induced by rapid application of intraluminal pre ssures of 40 cmH(2)O causing a reflex fall in arterial blood pressure. The depressor response to intestinal distention was abolished by intraperitonea l administration of capsaicin (5 mg/rat), which depletes neuropeptides such as substance P from the sensory neurons, on the mesenteric stalk and by ne onatal pretreatment with capsaicin (50 mg/kg, s.c.). Morphine (20 mg/kg, s. c.) reduced the depressor response following intestinal distention. At dose s of 3 mg/kg (i.v.) and higher, ZAL significantly reduced depressor respons e. The effect of morphine was reversed by naloxone (5 mg/kg, i.v.); the eff ect of ZAL was not affected. These results suggest that ZAL helps reduce th e visceral pain induced by noxious stimulus and that the antinociceptive ef fect of ZAL is not mediated by opioid receptors.