Houghton L A, Fell C, Whorwell P J, Jones I, Sudworth D P, Gale J D
Neurogastroenterology Unit, Academic Division of Medicine and Surgery, University of Manchester, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK.
Gut. 2007 Sep;56(9):1218-25. doi: 10.1136/gut.2006.110858. Epub 2007 Apr 19.
Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the alpha(2)delta ligand pregabalin reduces both visceral allodynia and hyperalgesia, but is inactive on basal sensitivity.
To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients.
Twenty-six patients with Rome-II-defined IBS (aged 18-46 years, 7 male) were included in a randomized, double-blind, placebo-controlled, parallel-group study in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1-3, 100 mg tid days 4-7, 150 mg tid days 8-11; fixed 200 mg tid days 12-21 +/-4) or placebo control. Rectal sensitivity was assessed using a barostat technique, in which sensory thresholds were determined using the ascending method of limits, followed by tracking both before and after treatment. Only patients with a pain threshold of <or=28 mmHg were included in the study.
Pregabalin significantly increased the sensory thresholds from baseline for first sensation (p = 0.045), desire to defecate (p = 0.008) and pain (p = 0.048) compared with placebo control. In addition, pregabalin significantly increased rectal compliance (p<0.0001), although this appeared to be unrelated to the changes in sensitivity. Despite the occurrence of mild dizziness and somnolence, pregabalin was generally well tolerated.
Pregabalin increased distension sensory thresholds to normal levels in IBS patients with rectal hypersensitivity. A concomitant increase in rectal compliance appeared to be unrelated to the reduction in sensitivity. These data suggest that alpha(2)delta ligands are worthy of further investigation in the treatment of visceral pain disorders, including IBS.
内脏高敏感性是肠易激综合征（IBS）的一个重要病理生理因素。临床前研究表明，α₂δ配体普瑞巴林可降低内脏痛觉过敏和痛觉超敏，但对基础敏感性无作用。
评估普瑞巴林对IBS高敏患者直肠扩张感知的影响。
26例符合罗马II标准的IBS患者（年龄18 - 46岁，男性7例）纳入一项随机、双盲、安慰剂对照、平行组研究，患者接受3周口服普瑞巴林（滴定剂量：第1 - 3天50 mg每日3次，第4 - 7天100 mg每日3次，第8 - 11天150 mg每日3次；第12 - 21天固定剂量200 mg每日3次±4）或安慰剂对照。采用气压测定技术评估直肠敏感性，使用极限递增法确定感觉阈值，然后在治疗前后进行跟踪。仅疼痛阈值≤28 mmHg的患者纳入研究。
与安慰剂对照相比，普瑞巴林显著提高了首次感觉（p = 0.045）、排便欲望（p = 0.008）和疼痛（p = 0.048）的基线感觉阈值。此外，普瑞巴林显著提高了直肠顺应性（p<0.0001），尽管这似乎与敏感性变化无关。尽管出现了轻度头晕和嗜睡，但普瑞巴林总体耐受性良好。
普瑞巴林可将直肠高敏IBS患者的扩张感觉阈值提高到正常水平。直肠顺应性的同时增加似乎与敏感性降低无关。这些数据表明，α₂δ配体在治疗包括IBS在内的内脏疼痛疾病方面值得进一步研究。
