Role of tachykinin NK2 receptors in normal and altered rectal sensitivity in rats

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Abstract
Irritable bowel syndrome is characterized by visceral hyperalgesia commonly associated with stress and inflammatory processes. We investigated the role of tachykinin NK2 receptors in the ability of trinitrobenzenesulphonic acid (TNBS) and stress to enhance the sensitivity of the rat rectum to distension using a selective tachykinin NK2 receptor antagonist (MEN 11420). Rats were fitted with electrodes implanted in the striated muscles of the abdomen. Rectal distension (RD) was performed with a balloon inflated by steps of 0.4 ml from 0 to 1.6 ml. Five groups were submitted to RD performed 3 days before and after intrarectal instillation of TNBS. Fifteen minutes before RD, rats were treated with saline or MEN 11420 (5–100 μg kg−1 i.v.). Two other groups, submitted to 2 h restraint or sham stress sessions were randomly treated i.v. with saline or MEN 11420 (10–200 μg kg−1) prior to RD applied 20 min later. The basal response to RD was characterized by a significant increase in the number of abdominal contractions. This response occurred with a threshold volume of 0.8 ml and was dose‐dependently reduced by MEN 11420 (5–100 μg kg−1 i.v.). Rectal inflammation lowered the volume of distension producing abdominal contractions to 0.4 ml (allodynia). This effect was either reduced or suppressed by MEN 11420. A similar allodynia was observed after a stress session and this effect was reduced (49%) or suppressed by MEN 11420 at 200 and 100 μg kg−1, respectively. Tachykinin NK2 receptors are involved in rectal hypersensitivity associated with inflammation and stress. British Journal of Pharmacology (2000) 129, 193–199; doi:10.1038/sj.bjp.0703040