Effects of Selective Blockade of 5-HT3 Receptors on Physiological Markers of Abdominal Pain in Conscious Dogs

摘要

Experiments on conscious dogs addressed the effects of blockade of type 3 serotonin receptors on visceromotor reactions and changes in heart rate (HR) initiated by nociceptive distension of the rectum. Distension of the rectal walls with pressures of 20-60 mmHg were found not to produce significant changes in the electromyographic activity of the abdominal muscles or HR. Distension of the intestine with a pressure of 80 mmHg and greater produced marked visceromotor reactions (contractions of the abdominal muscles) and increases in HR (tachycardia), which are regarded as markers for the occurrence of pain sensations. Use of these indicators allowed the first demonstration in conscious dogs of the dose-dependent antinociceptive effect of blockade of 5-HT3 receptors with granisetron. Administration of granisetron at doses of 0.25, 0.5, and 1.0 mg/kg was accompanied by prolonged (at least 90 min) decreases in visceromotor reactions to nociceptive rectal distension by 33.6 ± 9.2%, 58.0 ± 8.6%, and 76.7 ± 5.5% of baseline, respectively. In turn, the inhibitory effect of granisetron on tachycardia induced by painful rectal stimulation was seen only immediately after administration. Thus, studies on conscious dogs demonstrated the antinociceptive effect of granisetron in relation to abdominal pain, which may be relevant in the development of pharmacological agents to treat pain in patients with irritable bowel syndrome.