Responses of rat spinal neurons to distension of inflamed colon: role of tachykinin NK2 receptors

Tachykinin NK2 receptors are implicated in nociception and the control of i ntestinal motility. Here we examined their involvement in responses of spin al lumbosacral neurons with colon input to distension of normal or inflamed colon in anesthetized rats. The responses of single neurons to colorectal distension (5-80 mmHg), to electrical stimulation of the pelvic nerve (bypa ssing sensory receptors) and to somatic stimulation were characterized. The effect of cumulative doses of an NK2 receptor antagonist, MEN 11420 (10-10 00 mug kg(-1) IV), on responses to these stimuli was tested in control cond itions (n = 6), or 45 min after intracolonic instillation of acetic acid (n = 6). After colonic inflammation, neuronal responses to colorectal distens ion and pelvic nerve stimulation were significantly greater. MEN 11420 dose -dependently inhibited the enhanced responses to colorectal distension afte r inflammation (ID50 = 402 +/- 14 mug kg(-1)), but had no significant effec t on responses to pelvic nerve stimulation or distension of the normal colo n, suggesting a peripheral action selective for the inflamed colon. We conc lude that MEN 11420 possesses peripheral anti-hyperalgesic effects on neuro nal responses to colorectal distension. These results provide a neurophysio logical basis for a possible use of tachykinin NK2 receptor antagonists in treating abdominal pain in irritable bowel syndrome patients. (C) 2001 Else vier Science Ltd. All rights reserved.