Randomised clinical trial: Pregabalin attenuates experimental visceral pain through sub-cortical mechanisms in patients with painful chronic pancreatitis

S. S. Olesen, C. Graversen, A. E. Olesen, J. B. Frøkjær, O. Wilder-Smith, H. Van Goor, M. Valeriani, A. M. Drewes

Research output: Contribution to journalArticle

Abstract

Background Pregabalin has a broad spectrum of analgesic and antihyperalgesic activity in both basic and clinical studies. However, its mechanisms and sites of action have yet to be determined in humans. Aims To assess the antinociceptive effect of pregabalin on experimental gut pain in patients with visceral hyperalgesia due to chronic pancreatitis and to reveal putative changes in corresponding central pain processing as assessed by evoked brain potentials. Methods Thirty-one patients were randomly assigned to receive increasing doses of pregabalin or placebo for three consecutive weeks. Perceptual thresholds to electrical stimulation of the sigmoid with recording of corresponding evoked brain potentials were obtained at baseline and study end. The brain source localisations reflecting direct neuronal activity were fitted by a five-dipole model projected to magnetic resonance imaging of the individuals' brains. Results As compared to placebo, pregabalin significantly increased the pain threshold to electrical gut stimulation from baseline (P = 0.02). No differences in evoked brain potential characteristics were seen, neither after pregabalin nor placebo treatment (all P > 0.05). In agreement with this, brain source locations remained stable during study treatment (all P > 0.05). Conclusion Pregabalin was superior to placebo for attenuation of experimental visceral pain in chronic pancreatitis patients. We suggest its antinociceptive effects to be mediated primarily through sub-cortical mechanisms.

Original languageEnglish
Pages (from-to)878-887
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume34
Issue number8
DOIs
Publication statusPublished - Oct 2011

ASJC Scopus subject areas

  • Pharmacology (medical)

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