Peripheral Opioid Receptors Contribute to Exercise‐Induced Analgesia in Rats with Chronic Widespread Pain

Abstract

Fibromyalgia is characterized by chronic widespread musculoskeletal pain. Exercise has been shown to cause both analgesia and hyperalgesia in patients with fibromyalgia. Evidence suggests endorphins acting on central opioid receptors produce exercise‐induced analgesia, but the role of peripheral opioid receptors has not been investigated. We tested the hypothesis that peripheral opioid receptors contribute to exercise‐induced analgesia in a rat model of fibromyalgia. Chronic widespread pain was induced by acidic saline (pH 4) injections into the right gastrocnemius muscle of female Sprague Dawley rats. Control rats (n=10) then underwent four weeks (5 days/week; 30 min/day) of moderate‐intensity treadmill running. Treated rats (n=5) received injections of naloxone (120 μg), a nonspecific opioid receptor antagonist, in both gastrocnemius muscles prior to running. Mechanical hyperalgesia was quantified by measuring mechanical withdrawal threshold with von Frey filaments before and after each exercise bout. Changes in mechanical withdrawal threshold before and after running for control rats (week 1: 9 ± 5 mN; week 2: 10 ± 5 mN; week 3: 20 ± 5 mN) were significantly different from decreases in mechanical withdrawal threshold in the naloxone‐treated group (week 1: −13 ± 9 mN; week 2: −18 ± 8 mN; week 3: −13 ± 8 mN; all p<0.05). Values for week 4 were not significantly different between control (11 ± 5 mN) and treated (5 ± 6 mN; p>0.05). Findings suggest peripheral opioid receptors contribute to both exercise‐induced analgesia and exercise‐induced hyperalgesia in chronic pain conditions.