Pain inhibitory mechanisms and response to weak analgesics in patients with knee osteoarthritis

Eur J Pain. 2019 Nov;23(10):1904-1912. doi: 10.1002/ejp.1465. Epub 2019 Aug 19.

Abstract

Background: Conditioned pain modulation (CPM) and offset analgesia are different features of descending pain inhibition. This study investigated CPM, offset analgesia and clinical pain measures in patients with knee osteoarthritis (KOA) before and after treatment with the combination of a non-steroidal anti-inflammatory drug (NSAIDs) plus acetaminophen.

Methods: Forty-two patients with KOA received Ibuprofen 1.2 g/daily and acetaminophen 3.0 g/daily for three weeks. Before administration, CPM magnitude was assessed as the difference between cuff pain detection (cPDT) with and without a conditioning stimulus (evoked by tourniquet pain). Offset analgesia was assessed as the pain intensities evoked by a constant 46°C for 30-s stimulus compared to an offset analgesia paradigm of 46°C for 5-s, 47°C for 5-s and 46°C for 20-s. The worst pain within the last 24-hr and pain during activity were assessed before and after treatment.

Results: Clinical pain significantly decreased after treatment (p < 0.001) and less efficient CPM before treatment was associated with weaker analgesic effect (R = 0.354, p = 0.043). No significant modulation of CPM or offset analgesia was found for the treatment.

Conclusion: This study found that less efficient CPM is associated with reduced analgesic effect of NSAIDs plus acetaminophen in patients with KOA whereas the treatment did not modulate CPM nor offset analgesia magnitude.

Significance: This study demonstrated that conditioned pain modulation is correlated with the response to a standard pharmaceutical interventions treating osteoarthritis pain. Furthermore, we demonstrated that a decrease in clinical pain intensity is not associated with a normalization of conditioned pain modulation or offset analgesia, which questions if restoring these descending pain inhibitory mechanisms are pain intensity driven.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / therapeutic use*
  • Aged
  • Analgesia
  • Analgesics, Non-Narcotic / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arthralgia / drug therapy*
  • Arthralgia / physiopathology
  • Conditioning, Psychological
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ibuprofen / therapeutic use*
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Pain Management
  • Pain Measurement
  • Pain Threshold

Substances

  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen
  • Ibuprofen