Toulouse M, Coelho A M, Fioramonti J, Lecci A, Maggi C, Buéno L
Department of Pharmacology, INRA, France. Menarini Ricerche SpA., Florence, Italy.
Br J Pharmacol. 2000 Jan;129(1):193-9. doi: 10.1038/sj.bjp.0703040.
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 microg 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 microg 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 microg 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 microg kg(-1), respectively. Tachykinin NK2 receptors are involved in rectal hypersensitivity associated with inflammation and stress. British Journal of Pharmacology (2000) 129, 193 - 199
肠易激综合征的特征是内脏痛觉过敏，通常与应激和炎症过程相关。我们使用选择性速激肽NK2受体拮抗剂（MEN 11420），研究了速激肽NK2受体在三硝基苯磺酸（TNBS）和应激增强大鼠直肠对扩张的敏感性中的作用。给大鼠腹部的横纹肌植入电极。用气球以0.4 ml的步长从0膨胀至1.6 ml进行直肠扩张（RD）。五组在直肠内注入TNBS前后3天进行RD。在RD前15分钟，给大鼠静脉注射生理盐水或MEN 11420（5 - 100 μg kg⁻¹）。另外两组，分别接受2小时的束缚或假应激处理，在20分钟后进行RD前，随机静脉注射生理盐水或MEN 11420（10 - 200 μg kg⁻¹）。对RD的基础反应表现为腹部收缩次数显著增加。这种反应在扩张体积为0.8 ml时出现，并且被MEN 11420（5 - 100 μg kg⁻¹静脉注射）剂量依赖性地降低。直肠炎症将引起腹部收缩的扩张体积降低至0.4 ml（痛觉过敏）。MEN 11420可减轻或抑制这种作用。应激处理后观察到类似的痛觉过敏，并且分别在MEN 11420剂量为200和100 μg kg⁻¹时，这种作用降低（49%）或被抑制。速激肽NK2受体参与了与炎症和应激相关的直肠超敏反应。《英国药理学杂志》（2000年）129卷，193 - 199页
