Acute Resistance Exercise Induces Antinociception by Activation of the Endocannabinoid System in Rats

Abstract

Background Resistance exercise (RE) is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength and metabolism. RE has been increasingly prescribed for pain relief. However, the endogenous mechanisms underlying this antinociceptive effect are still largely unexplored. Thus, we investigated the involvement of the endocannabinoid system in RE-induced antinociception. Methods Male Wistar rats were submitted to acute RE in a weight-lifting model. The nociceptive threshold was measured by a mechanical nociceptive test (paw pressure) before and after exercise. To investigate the involvement of cannabinoid receptors and endocannabinoids in RE-induced antinociception, cannabinoid receptor inverse agonists, endocannabinoid metabolizing enzyme inhibitors and an anandamide reuptake inhibitor were injected before RE. After RE, CB1 cannabinoid receptors were quantified in rat brain tissue by Western blot and immunofluorescence. In addition, endocannabinoid plasma levels were measured by isotope dilution-liquid chromatography mass spectrometry. Results RE-induced antinociception was prevented by preinjection with CB1 and CB2 cannabinoid receptor inverse agonists. By contrast, preadministration of metabolizing enzyme inhibitors and the anandamide reuptake inhibitor prolonged and enhanced this effect. RE also produced an increase in the expression and activation of CB1 cannabinoid receptors in rat brain tissue and in the dorsolateral and ventrolateral periaqueductal regions and an increase of endocannabinoid plasma levels. Conclusion The present study suggests that a single session of RE activates the endocannabinoid system to induce antinociception.

Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena

“…This effect is prevented by systemic and central blockade with cannabinoid receptor antagonists (AM251 and AM630) (Galdino et al . , b). Since endocannabinoids have synergistic interactions with opioids to produce antinociception (Navarro et al .…”

Animal models of resistance exercise and their application to neuroscience research

“…Similar results are observed in animal models, with several recent studies demonstrating the antinociceptive effects of resistance exercise (Table 2). These studies have shown that resistance exercise as modeled by squat-based methods increases nociceptive thresholds in tail-flick and paw-withdrawal procedures relative to sedentary controls (de Souza et al, 2013; Galdino et al, 2010, 2014a, 2014b). These antinociceptive effects are apparent immediately following an acute bout of exercise, but tend to diminish with repeated training (i.e., longer than 45 days; Galdino et al, 2010).…”

“…Electric shock is known to induce antinociception in laboratory animals through the activation and involvement of the endogenous opioid system (Nabeshima et al, 1985). As a result, the findings relating exercise-induced antinociception to opioid signaling may be affected by the use of electric shock during resistance exercise; however, a recent study demonstrated antinociception in resistance trained subjects relative to sedentary controls that received electrical stimulation “yoked” to their resistance partners (Galdino et al, 2014b). Future studies that maintain behavior through the use of non-noxious stimuli will be needed to fully elucidate the mechanisms mediating exercise-induced antinociception.…”

Nonpharmacological Interventions in Targeting Pain-Related Brain Plasticity

“…Similarly, both aerobic exercise and resistance training in rats were shown to be associated with increased nociceptive thresholds as well as increased CB1R levels in the PAG [110, 111]. …”