title: Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients.
abstract: BACKGROUND
  Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders) to placebo or pregabalin treatment.
  
  
  METHODS
  This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15) or placebo (n=12; n=17) treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT) in dermatomes C5 (generalized effects) and Ventral T10 (segmental effects). Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM) paradigm.
  
  
  RESULTS
  Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA) vs placebo responders (-0.1 mA; P=0.015). This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9%) vs placebo responders (-17%; P<0.001). CPM changed significantly vs baseline only for pregabalin responders (P=0.006).
  
  
  CONCLUSIONS
  This hypothesis-generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study.
authors.affiliation: Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Stefan Aw
authors.initials: SA
authors.lastname: Bouwense
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Søren S
authors.initials: SS
authors.lastname: Olesen
authors.affiliation: Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Pain and Nociception Neuroscience Research Group, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Oliver Hg
authors.initials: OH
authors.lastname: Wilder-Smith
keywords: central sensitization; chronic pain treatment; chronic pancreatitis; placebo; pregabalin; quantitative sensory testing