Effect of a second-generation Alpha2Delta ligand, Pregabalin on visceral sensation in hypersensitive patients with irritable bowel syndrome

Lesley A Houghton ^1*, Catherine Fell ¹, Peter J Whorwell ¹, ieuan Jones ², David P Sudworth ² and Jeremy D Gale ²

¹ Wythenshawe Hospital, United Kingdom
² Pfizer Global R and D, United Kingdom

^* To whom correspondence should be addressed. E-mail: lesley.houghton{at}manchester.ac.uk.

Accepted 11 April 2007

Abstract

Background: Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the alpha2delta 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 three weeks oral pregabalin (titrated: 50mg tid days 1-3, 100mg tid days 4-7, 150mg tid days 8-11; fixed 200mg 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 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 alpha2delta ligands are worthy of further investigation in the treatment of visceral pain disorders, including IBS.

Keywords: alpha2delta ligand, irritable bowel syndrome, pregabalin, visceral sensitivity

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