NEUROGASTROENTEROLOGY

Effect of a second-generation ₂ ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome

L A Houghton¹, C Fell¹, P J Whorwell¹, I Jones², D P Sudworth², J D Gale²

¹ Neurogastroenterology Unit, Academic Division of Medicine and Surgery, University of Manchester, Wythenshawe Hospital, Manchester, UK
² Pfizer 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; Lesley.Houghton{at}manchester.ac.uk

Background: Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the ₂ 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 ₂ ligands are worthy of further investigation in the treatment of visceral pain disorders, including IBS.

Abbreviations: BOP, basal operating pressure; CGRP, calcitonin gene-related peptide; CNS, central nervous system; GABA, -aminobutyric acid; IBS, irritable bowel syndrome; LPS, lipopolysaccharide

Keywords: pregabalin; 2 ligands; visceral sensitivity; irritable bowel syndrome

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

2 ligand: a new, smart pill for visceral pain in patients with hypersensitive irritable bowel syndrome?

Michael Camilleri
Gut 2007 56: 1337-1338. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Lacy, B. E., Weiser, K., De Lee, R. (2009). Review: The treatment of irritable bowel syndrome. Therapeutic Advances in Gastroenterology 2: 221-238 [Abstract]  
• Lindstrom, E., Ravnefjord, A., Brusberg, M., Hjorth, S., Larsson, H., Martinez, V. (2009). The Selective 5-Hydroxytryptamine 1A Antagonist, AZD7371 [3(R)-(N,N-Dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate Monohydrate] (Robalzotan Tartrate Monohydrate), Inhibits Visceral Pain-Related Visceromotor, but Not Autonomic Cardiovascular, Responses to Colorectal Distension in Rats. J. Pharmacol. Exp. Ther. 329: 1048-1055 [Abstract] [Full Text]  
• Camilleri, M. (2007). {alpha}2{delta} ligand: a new, smart pill for visceral pain in patients with hypersensitive irritable bowel syndrome?. Gut 56: 1337-1338 [Full Text]