Sensitization of enteric reflexes in the rat colon in vitro

We have investigated sensitization of reflexes in the isolated rat colon in order to develop a model that might prove useful for investigating how the sensitivity of enteric reflexes can be altered by prior stimulation. Records were taken of circular muscle tension, 7–10 mm oral and anal to radial distension exerted by a hook passed through the wall of the colon. A test stimulus of 1.5 g produced consistent contractions both oral and anal to the distension. A conditioning protocol, consisting of repeated application of 3 g for 30 s with 30 s between the stimuli for 30 min, doubled the amplitudes of reflex contractions that were evoked by the test stimuli but did not change the sensitivity of the muscle to the direct action of carbachol. The enhanced responses persisted for at least 40 min. The enhancement of reflexes was not reduced by antagonists of tachykinin NK3 receptors or of 5-HT3 receptors, but the reflex oral to stimulation was reduced by NK1 and NK3 antagonists added together. Sensitization was abolished by the cyclo-oxygenase and thromboxane synthase inhibitor, indomethacin. We conclude that sensitization can be reliably induced in vitro and that the model described in the present work can be used to investigate drugs that interfere with the sensitization process.