title: Randomised clinical trial: pregabalin attenuates experimental visceral pain through sub-cortical mechanisms in patients with painful chronic pancreatitis.
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Denmark. sso@mech-sense.com
authors.forename: S S
authors.initials: SS
authors.lastname: Olesen
authors.forename: C
authors.initials: C
authors.lastname: Graversen
authors.forename: A E
authors.initials: AE
authors.lastname: Olesen
authors.forename: J B
authors.initials: JB
authors.lastname: Frøkjaer
authors.forename: O
authors.initials: O
authors.lastname: Wilder-Smith
authors.forename: H
authors.initials: H
authors.lastname: van Goor
authors.forename: M
authors.initials: M
authors.lastname: Valeriani
authors.forename: A M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D050500:Pancreatitis, Chronic / Q000150:complications / Q000188:drug therapy*; D000069583:Pregabalin; D016896:Treatment Outcome; D059265:Visceral Pain / Q000139:chemically induced / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid