Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial

PLoS One. 2012;7(8):e42096. doi: 10.1371/journal.pone.0042096. Epub 2012 Aug 6.

Abstract

Background: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST).

Methods: This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups.

Results: 64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation.

Conclusion: Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain.

Trial registration: ClinicalTrials.gov NCT00755573.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use*
  • Case-Control Studies
  • Central Nervous System Sensitization / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain Threshold / drug effects
  • Pancreatitis, Chronic / drug therapy*
  • Pancreatitis, Chronic / physiopathology*
  • Placebos
  • Pregabalin
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Analgesics
  • Placebos
  • Pregabalin
  • gamma-Aminobutyric Acid

Associated data

  • ClinicalTrials.gov/NCT00755573

Grants and funding

Supported by a free grant from Pfizer Research and Development, Hertha Christensen’s Foundation, and Christenson-Ceson’s Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.