Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study

Pain Pract. 2018 Apr;18(4):418-430. doi: 10.1111/papr.12613. Epub 2017 Nov 15.

Abstract

Background: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.

Methods: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten chronic fatigue syndrome (CFS)/fibromyalgia (FM) patients, 11 rheumatoid arthritis (RA) patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/mL Naloxone) and placebo (2 mL Aqua) group. Pressure pain thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned pain modulation (CPM) efficacy and deep tissue pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.

Results: Deep tissue pain pressure was lower and temporal summation higher in CFS/FM (P = 0.002 respectively P = 0.010) and RA patients (P = 0.011 respectively P = 0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (P time = 0.034). Accordingly, PPTs increased after placebo (P time = 0.015), and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, deep tissue pain, temporal summation or CPM in the control group.

Conclusions: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

Keywords: central sensitization; chronic fatigue syndrome; fibromyalgia; opioids; pain assessment; rheumatoid arthritis.

Publication types

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

MeSH terms

  • Adult
  • Analgesics, Opioid / therapeutic use*
  • Arthritis, Rheumatoid / complications*
  • Central Nervous System Sensitization / drug effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Fatigue Syndrome, Chronic / complications*
  • Female
  • Fibromyalgia / complications*
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / etiology
  • Male
  • Middle Aged
  • Morphine / therapeutic use*
  • Naloxone / therapeutic use
  • Narcotic Antagonists / therapeutic use
  • Pain Measurement / methods
  • Pain Threshold / drug effects

Substances

  • Analgesics, Opioid
  • Narcotic Antagonists
  • Naloxone
  • Morphine