naloxone and Arthritis--Rheumatoid

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.. 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.. 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.. 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.

Topics: Adult; Analgesics, Opioid; Arthritis, Rheumatoid; Central Nervous System Sensitization; Cross-Over Studies; Double-Blind Method; Fatigue Syndrome, Chronic; Female; Fibromyalgia; Humans; Hyperalgesia; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain Threshold

We have previously shown that there is deficient hypothalamic-pituitary-adrenal (HPA) responsiveness in rheumatoid arthritis (RA) patients. The basis for this deficient response is not known. The purpose of the project was to investigate whether the defective HPA response in RA patients is the result of increased endogenous opioid tone secondary to chronic pain which can suppress corticotrophin-releasing hormone (CRH) production. We conducted a double-blind placebo-controlled cross-over trial to study the effect of the opiate antagonist, naloxone, on psychometric function together with plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin. Seven RA patients with active and established disease and eight healthy controls were studied. Each received either a bolus i.v. infusion of 20 mg naloxone or normal saline. After at least 72 h, they received naloxone if they had previously received normal saline or vice versa. The pain score was statistically significantly higher at baseline in the RA group compared with controls (5.7 +/- 3.25 vs 0.35 +/- 0.21, P < 0.001). No difference was found in the other psychometric assessments throughout the study. Patients receiving normal saline did not show any significant change in cortisol or ACTH. Cortisol and ACTH showed a sharp and significant rise after naloxone treatment in both RA and normal subjects (P < 0.001 and P < 0.01), but no difference was observed between the two groups. The mean prolactin level showed no significant change in both groups after any treatment. We conclude that endogenous opioid tone does not appear to be a major contributor to the HPA defect in RA. However, the number of patients studied was small and this result will require confirmation from larger trials.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Arthritis, Rheumatoid; Cross-Over Studies; Double-Blind Method; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid Peptides; Pituitary-Adrenal System; Prolactin; Psychometrics

This study was designed to examine the effects of aspirin, naloxone and placebo treatment on serum beta-endorphin concentration and joint pain in patients with rheumatoid arthritis (RA). Ten patients with definite or classical RA were studied. All treatments were administered in a randomized sequence. On each study day, the following measurements were carried out at specified time intervals: serum beta-endorphin concentration, serum salicylate concentration and joint pain score on a visual analogue horizontal scale. We conclude that in patients with rheumatoid arthritis suffering from chronic joint pain, serum beta-endorphin does not appear to play a role in pain relief.

Topics: Arthritis, Rheumatoid; Aspirin; beta-Endorphin; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Humans; Naloxone; Pain; Pain Measurement; Placebos; Random Allocation