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 intestinal motility. Here we examined their involvement in responses of spinal 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 (bypassing sensory receptors) and to somatic stimulation were characterized. The effect of cumulative doses of an NK2 receptor antagonist, MEN 11420 (10-1000 microg kg(-1) IV), on responses to these stimuli was tested in control conditions (n=6), or 45 min after intracolonic instillation of acetic acid (n=6). After colonic inflammation, neuronal responses to colorectal distension and pelvic nerve stimulation were significantly greater. MEN 11420 dose-dependently inhibited the enhanced responses to colorectal distension after inflammation (ID50=402+/-14 microg kg(-1)), but had no significant effect on responses to pelvic nerve stimulation or distension of the normal colon, suggesting a peripheral action selective for the inflamed colon. We conclude that MEN 11420 possesses peripheral anti-hyperalgesic effects on neuronal responses to colorectal distension. These results provide a neurophysiological basis for a possible use of tachykinin NK2 receptor antagonists in treating abdominal pain in irritable bowel syndrome patients.
Laird
J M
JM
Department of Physiology, University of Alcalá, Alcalá de Henares, E-28871, Madrid, Spain. jennifer.laird@uah.es
Olivar
T
T
Lopez-Garcia
J A
JA
Maggi
C A
CA
Cervero
F
F
D000818:Animals; D003092:Colitis / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D009474:Neurons / Q000473:pathology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
C107754:MEN 11420; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2