ENDOGENOUS OPIOID TONE IN PATIENTS WITH RHEUMATOID ARTHRITIS

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 purposeof the project was to investigate whether the defective HPAresponse in RA patients is the result of increased endogenousopioid tone secondary to chronic pain which can suppress corticotrophin-releasinghormone (CRH) production. We conducted a double-blind placebo-controlledcross-over trial to study the effect of the opiate antagonist,naloxonc, on psychometric function together with plasma adrenocorticotrophichormone (ACTH), cortisol and prolactin. Seven RA patients withactive and established disease and eight healthy controls werestudied. Each received either a bolus i.v. infusion of 20 mgnaloxone or normal saline. After at least 72 h, they receivednaloxone if they had previously received normal saline or viceversa. The pain score was statistically significantly higherat baseline in the RA group compared with controls (5.7 ±3.25 vs 0.35 ± 0.21, P < 0.001). No difference wasfound in the other psychometric assessments throughout the study.Patients receiving normal saline did not show any significantchange in cortisol or ACTH. Cortisol and ACTH showed a sharpand significant rise after naloxone treatment in both RA andnormal subjects (P < 0.001 and P < 0.01), but no differencewas observed between the two groups. The mean prolactin levelshowed no significant change in both groups after any treatment.We conclude that endogenous opioid tone does not appear to bea major contributor to the HPA defect in RA. However, the numberof patients studied was small and this result will require confirmationfrom larger trials. KEY WORDS: Rheumatoid arthritis, Endogenous opioid, Opiate, Hypothalamus-pituitary-adrenal axis, Cortisol, Naloxone, ACTH, Prolactin