Endocannabinoid and Opioid System Interactions in Exercise-Induced Hypoalgesia

Abstract

Objective: The purpose of this study was to examine the interaction between the endogenous opioid and endocannabinoid (eCB) systems in a pain modulatory process known as exercise-induced hypoalgesia (EIH).

Design: Randomized controlled trial.

Setting: Clinical research unit in a hospital.

Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study.

Methods: Participants were administered (randomized, double-blind, counterbalanced procedure) an opioid antagonist (i.e., naltrexone) and a placebo prior to performing pain testing and isometric exercise.

Results: Results indicated that 2-arachidonoylglycerol (2-AG) and 2-oleoylglycerol (2-OG) increased significantly (P < 0.05) following exercise in both placebo and naltrexone conditions. In comparison, N-arachidonylethanolamine (AEA) and oleoylethanolamine (OEA) increased significantly (P < 0.05) following exercise in the placebo condition but not the naltrexone condition. There were no significant (P > 0.05) differences in palmitolethanolamine (PEA) between the placebo and naltrexone conditions.

Conclusions: As reductions in pain (i.e., EIH) were observed following both conditions, these results suggest that the opioid system may not be the primary system involved in exercise-induced hypoalgesia and that 2-AG and 2-OG could contribute to nonopioid exercise-induced hypoalgesia. Moreover, as exercise-induced increases in AEA and OEA were blocked by naltrexone pretreatment, this suggests that the opioid system may be involved in the increase of AEA and OEA following exercise.

Keywords: 2-AG; AEA; EIH Mechanisms; Isometric Exercise; Pain Modulation.

Figure 1

Schematic of experimental procedures. NAL = naltrexone; PLA = placebo.

Figure 2

Percent change in circulating concentrations of eCB and related lipids before and after pain testing and exercise in placebo and naltrexone conditions. Postpain % change values refer to the eCB response to pain testing as a percentage change from baseline plasma concentrations. Postexercise % change values refer to the eCB response to exercise as a percentage change from postpain testing plasma concentrations. A) Significant condition × time interaction effect (P < 0.05; denoted +) for AEA. B) Significant condition × time interaction effect (P < 0.05; denoted +) for OEA. C) No significant main effect for time or condition or significant condition × time interaction found for PEA. D) Significant main effect for time (P < 0.05, denoted *) found for 2-AG. E) Significant main effect for time (P < 0.05; denoted *) found for 2-OG. Error bars are ± SEM. 2AG = 2-arachidonoylglycerol; 2OG = 2-oleoylglycerol; AEA = N-arachidonylethanolamine; OEA = oleoylethanolamine; PEA = palmitoylethanolamine.