Effect of a second-generation α2δ ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome
- 1Neurogastroenterology Unit, Academic Division of Medicine and Surgery, University of Manchester, Wythenshawe Hospital, Manchester, UK
- 2Pfizer Global R&D, Sandwich, Kent, UK
- Correspondence to:
Dr L A Houghton
Neurogastroenterology Unit, Academic Division of Medicine and Surgery, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK;
- Received 11 September 2006
- Accepted 11 April 2007
- Revised 3 April 2007
- Published Online First 19 April 2007
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.
- BOP, basal operating pressure
- CGRP, calcitonin gene-related peptide
- CNS, central nervous system
- GABA, γ-aminobutyric acid
- IBS, irritable bowel syndrome
- LPS, lipopolysaccharide
Published Online First 19 April 2007