Delvaux M, Louvel D, Mamet J P, Campos-Oriola R, Frexinos J
Laboratory of Digestive Motility, Gastroenterology Unit, Toulouse, France.
Aliment Pharmacol Ther. 1998 Sep;12(9):849-55. doi: 10.1046/j.1365-2036.1998.00375.x.
Visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3 receptors on afferent nerves may modulate visceral sensitivity and be the target of new treatments for irritable bowel syndrome.
To evaluate the effects of alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic distension by patients with irritable bowel syndrome, and on the colonic compliance to distension with a barostat.
Twenty-five irritable bowel syndrome patients were included in a randomized double-blind parallel group trial; data were available for 22 (Rome criteria; 48 +/- 11 years: 13 men and nine women). Patients were treated for 7 days with placebo (n = 6), alosetron 0.25 mg b.d. (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was placed in the left colon. On day 7, after an overnight fast, isobaric phasic distensions were performed (4 mmHg steps, 5 min) up to the step triggering a sensation of abdominal pain.
Groups were comparable at inclusion (age, sex, symptoms, bowel habits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pain. However, bag volumes were significantly increased. At the first sensation threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (P = 0.017). Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on alosetron 0.25 mg b.d. and to 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d.
Alosetron increases the compliance of the colon to distension, and could thereby contribute to changes in perception of colonic distension and improvement in the symptoms of irritable bowel syndrome.
如气囊扩张研究所示，内脏高敏感性在肠易激综合征的病理生理学中起主要作用。传入神经上的5-羟色胺3（5-HT3）受体可能调节内脏敏感性，并且是肠易激综合征新治疗方法的靶点。
评估强效选择性5-HT3拮抗剂阿洛司琼对肠易激综合征患者结肠扩张感知以及对通过恒压器测定的结肠扩张顺应性的影响。
25例肠易激综合征患者纳入一项随机双盲平行组试验；22例（罗马标准；48±11岁：13例男性和9例女性）数据可用。患者接受安慰剂（n = 6）、阿洛司琼0.25mg每日2次（n = 8）或阿洛司琼4mg每日2次（n = 8）治疗7天。在第6天，将一个恒压器气囊置于左结肠。在第7天，经过一夜禁食后，进行等压阶段性扩张（以4mmHg步长，5分钟），直至引发腹痛感觉的步长。
入组时各治疗组具有可比性（年龄、性别、症状、排便习惯）。在首次感觉到腹痛时，各治疗组在气囊内记录的压力无差异。然而，气囊容积显著增加。在首次感觉阈值时，阿洛司琼0.25mg每日2次和4mg每日2次分别记录到中位数容积差异为61mL和90mL（P = 0.028）。在腹痛阈值时，这些差异分别为71mL（P = 0.039）和84mL（P = 0.017）。结肠顺应性从安慰剂组的5.9mL/mmHg增加至阿洛司琼0.25mg每日2次组的7.6mL/mmHg以及阿洛司琼4mg每日2次组的9.8mL/mmHg（P = 0.034）。
阿洛司琼增加结肠对扩张的顺应性，从而可能有助于改变结肠扩张的感知并改善肠易激综合征的症状。
