Engaging in regular aerobic exercise may provide limited, direct effects on morphine analgesic responses, and this training can provide analgesia similar to that observed with a low dose of intravenous morphine, according to research results published in Pain.

Researchers conducted a randomized controlled trial (ClinicalTrials.gov identified NCT02469077) to evaluate the effects of structured aerobic exercise training on chronic low back pain, the role of endogenous opioid mechanisms, and the effect of this intervention on responsiveness to opioid analgesics.

Morphine, naloxone, and a placebo were administered to patients in a double-blinded crossover design in a randomized, counterbalanced order over the course of 3 separate but identical laboratory sessions conducted over a 10-day period. Participants (N=83) had chronic low back pain and were not currently using opioid analgesics on a daily basis. As-needed opioid use was discontinued 3 days before each lab session, while nonsteroidal anti-inflammatory drug or over-the-counter analgesic use was discontinued for 12 hours prior.

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Participants were then randomly assigned 1:1 to either the exercise intervention (n=38) or a usual activity control group (n=45).

Between-group baseline characteristics were similar; most participants were non-Hispanic White women. Chronic pain was moderate in intensity and had a long duration. Over 90% of participants in the exercise group (94.7%) completed the full 18 sessions, with a mean time spent in the prespecified target heart rate of 21.1 (±4.65) minutes.

At baseline, morphine effect values for evoked and chronic back pain measures did not differ in either group. After the intervention, a significant Group X Sex interaction was observed (F(1,68)=4.15; P =.046). For evoked pain measures, there was a “marginally significant” Group X Sex interaction observed for heat pain threshold (F(1,72)=2.90; P =.093).

Investigators also compared the difference between pre- and post-intervention pain ratings across groups. Results of this analysis indicated that evoked pain measures in the exercise group following the intervention were significantly closer to—and lower than, in some cases—pre-intervention pain responses achieved with 7 mg intravenous morphine. These pain ratings included ratings of pain threshold, sensory and visual analog scale (VAS) intensity, back pain intensity, and placebo condition pain responses.

Collected data also allowed researchers to examine whether increases in endogenous opioid function over time was associated with a decrease in opioid analgesic response over the same period. Investigators conducted a series of hierarchical multiple regressions, the results of which confirmed that larger endogenous opioid function increases between pre- and post-intervention were associated in greater pre-post intervention reductions in morphine analgesic responses; this was independent of the influence of intervention assignment and sex, age, and body mass index confounders.

Study limitations include a lack of generalizability to patients outside of the participant profile and limited statistical power due to the challenges of recruiting for the study.

“The current findings showed limited direct effects of aerobic exercise training on morphine analgesic responses,” the researchers concluded. “These results imply that the degree of chronic back pain relief achievable with a systematic aerobic exercise training program alone may not be dissimilar to the relief attained with moderate dose opioid analgesic medications in the absence of an exercise program.”

“Given the better risk/benefit ratio of exercise training relative to chronic administration of opioid analgesics,” they continued, “these findings could represent a practical clinical implication of the present results.”

Future research should assess the potential applications of these findings in the context of precision pain medicine protocols.


Bruehl S, Burns JW, Koltyn K, et al. Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? a randomized controlled trial. Published online December 15, 2020. Pain. doi:10.1097/j.pain.0000000000002165

This article originally appeared on Clinical Pain Advisor