Endocannabinoid and Opioid System Interactions in Exercise-Induced Hypoalgesia

Abstract

Anatomical, biochemical, and pharmacological evidence indicates bidirectional interactions between endocannabinoid (eCB) and opioid systems, but there are conflicting results concerning whether opioid antagonists block cannabinoid analgesia. Moreover, the interaction between these two systems in specific pain modulatory processes such as exercise-induced hypoalgesia (EIH) has not been examined. PURPOSE: To examine whether an opioid antagonist influenced pain and eCB responses following exercise in healthy young adults. METHODS: Fifty-eight men and women (m = 21 yrs; sd = 3) were administered an opioid antagonist {50 mg naltrexone (NAL)} and a placebo (PLA) via a randomized, double-blind counterbalanced procedure. Pain testing (i.e., noxious heat and pressure) and blood draws were completed before and following 3-min of isometric exercise at 25% maximal voluntary contraction. Data were analyzed with repeated measures ANOVAs. RESULTS: The results indicated that EIH (i.e., reduction in pain following exercise) occurred in both PLA and NAL conditions. Serum concentrations of eCBs and related lipids were all increased after exercise; these increases were not significantly different (p > 0.05) between PLA and NAL conditions for the eCBs N-arachidonylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG); or for non-eCB analogs palmitoylethanolamide (PEA) and 2-oleoylglycerol (2-OG). There was, however, a significant condition x time interaction (p <0.05) for oleoylethanolamine (OEA), a lipid known to be involved in satiety, indicating a significant increase in OEA following exercise in the PLA condition but not in the NAL condition. CONCLUSIONS: These results confirm earlier findings that exercise rapidly increases circulating concentrations of the eCBs but do not support a role for mu opiate receptor signaling in this effect. Intriguingly, however, exercise-induced increases in OEA were reduced by NAL, suggesting a role for opiate signaling in its regulation. Supported by NIH grant R21AR057159 and 1UL1RR025011 and the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin