Background: Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the α₂δ 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 ⩽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 α₂δ ligands are worthy of further investigation in the treatment of visceral pain disorders, including IBS.