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Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome.

Houghton LA, Fell C, Whorwell PJ, Jones I, Sudworth DP, Gale JD

Neurogastroenterology Unit, Academic Division of Medicine and Surgery, University of Manchester, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK. Lesley.Houghton@manchester.ac.uk

BACKGROUND: 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. AIM: To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Published 16 August 2007 in Gut, 56(9): 1218-25.
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Irritable Bowel Syndrome Research Today Archive:

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Irritable Bowel Syndrome Books

Breaking the Bonds of Irritable Bowel Syndrome: A Psychological Approach to Regaining Control of Your Life

Breaking the Bonds of Irritable Bowel Syndrome: A Psychological Approach to Regaining Control of Your Life