Hasler W L, Soudah H C, Owyang C
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
J Pharmacol Exp Ther. 1994 Mar;268(3):1206-11.
Irritable bowel syndrome (IBS) patients exhibit enhanced sensitivity to rectal distention. The somatostatin analog reduces perception of rectal distention in healthy volunteers without modifying rectal resistance. We evaluated whether octreotide has similar effects on rectal perception and resistance in diarrhea-prone IBS patients. Octreotide (100 micrograms s.c.) and placebo were injected in double-blind fashion in eight IBS patients. Rectal balloons measured volumes that evoked increasing levels of perception and intrarectal pressures. After placebo, threshold perception, pressure, urgency and maximal tolerated volume were reported at 18 +/- 5, 46 +/- 8, 72 +/- 7 and 102 +/- 10 ml by the IBS patients, values less than we have observed in healthy volunteers. With octreotide, these sensations were perceived at higher volumes (40 +/- 10, 89 +/- 16, 167 +/- 20 and 202 +/- 25 ml, P < .05) that approximated responses in healthy volunteers. IBS patients exhibited higher rectal pressures at each volume and showed a trend to higher rectal resistance (0.13 +/- 0.02 mmHg/ml) than we have observed in healthy volunteers. These abnormalities were normalized by octreotide. Octreotide did not block the rectoanal inhibitory reflex confirming a lack of effect on local rectal reflex arcs. As with healthy volunteers, IBS patients with diarrhea experience reduced perception of rectal distention after octreotide. Octreotide also reduces elevated rectal pressures in IBS patients, in contrast to healthy volunteers. Thus, octreotide shows potential therapeutic benefit in IBS via dual effects on visceral afferent pathways and rectal wall stiffness.
肠易激综合征(IBS)患者对直肠扩张表现出增强的敏感性。生长抑素类似物可降低健康志愿者对直肠扩张的感知,而不改变直肠阻力。我们评估了奥曲肽对腹泻型IBS患者的直肠感知和阻力是否有类似作用。对8例IBS患者以双盲方式注射奥曲肽(100微克皮下注射)和安慰剂。直肠气囊测量引起不同感知水平和直肠内压力的容积。注射安慰剂后,IBS患者报告的阈感知、压力、急迫感和最大耐受容积分别为18±5、46±8、72±7和102±10毫升,这些值低于我们在健康志愿者中观察到的值。使用奥曲肽后,这些感觉在更高的容积(40±10、89±16、167±20和202±25毫升,P<.05)时被感知,接近健康志愿者的反应。IBS患者在每个容积下均表现出较高的直肠压力,并且与我们在健康志愿者中观察到的相比,显示出直肠阻力升高的趋势(0.13±0.02毫米汞柱/毫升)。这些异常通过奥曲肽得以正常化。奥曲肽未阻断直肠肛门抑制反射,证实其对局部直肠反射弧无作用。与健康志愿者一样,腹泻型IBS患者在使用奥曲肽后对直肠扩张的感知降低。与健康志愿者相反,奥曲肽还降低了IBS患者升高的直肠压力。因此,奥曲肽通过对内脏传入通路和直肠壁硬度的双重作用,在IBS中显示出潜在的治疗益处。