[The effects of selective 5HT3 receptor blockade on physiological markers of abdominal pain in awake dogs].

In awake dogs, the visceromotor and cardioautonomic responses to the rectal balloon distension were studied before and after intravenous administration of a selective 5HT3 receptor antagonist granisetron. It was shown that balloon distension level up to 60 mmHg caused neither noticeable muscle responses nor substantial changes in heart rate. In turn, distending pressures of 80 mmHg and higher induced vigorous abdominal muscle contractions and tachycardia that were graded with increasing intensities of stimulation. Thus, the rectal stimulation with pressures 80 mmHg and more produced the changes in visceromotor and cardiovascular indices which could be considered as suitable indicators of visceral nociception in conscious animals. Based on monitoring of these physiological markers in a model of abdominal pain the dose-dependent antinociceptive effect of granisetron in awake dogs has been demonstrated for the first time. It was determined that granisetron in doses of 0.25, 0.5 or 1.0 mg/kg induced correspondingly 33.6 +/- 9.2, 58.0+/- 8.6 [see text] 76.7 +/- 5.5 % decrease in visceromotor response of dogs to nociceptive visceral stimulation. The effect occurred immediately after the drug administration and was lasting more than 90 min. In turn, the dose-dependent suppression of the rectal distension-induced tachycardia was less prominent and only observed during the initial period of granisetron action. The described model of abdominal pain in awake dogs might be useful for preclinical screening of new pharmacological substances, whereas the obtained data could contribute to the development of more efficient analgesics aimed in patients with irritable bowel syndrome.