Abstract
As exercise intervention solely for pain reduction is relatively new, the available research still leaves an incomplete picture of responsible mechanisms and pathways. Nonetheless, evidence indicates that exercise-induced analgesia involves activation of the endocannabinoid (eCB) system. The present study investigated the role of the eCB system on the antihyperalgesic effect of high-intensity swimming exercise (HISE) in an animal model of peripheral persistent inflammation. Male Swiss mice were allocated to non-exercised and exercised groups and subjected to subcutaneous intraplantar injection (i.pl.) of a single dose of complete Freund's adjuvant (CFA) to induce inflammatory pain. Cumulative HISE was performed once a day, and mechanical hyperalgesia and edema were evaluated 0.5 hour after HISE for seven consecutive days. To investigate the role of the eCB system on the antihyperalgesic effect of HISE, non-exercised and exercised mice received intraperitoneal (ip), intrathecal (i.t.) or i.pl. injections of vehicle, AM281 (a CB1 cannabinoid receptor antagonist) or AM630 (a CB2 cannabinoid receptor antagonist) from the 3rd to 5th day after CFA injection. Mechanical hyperalgesia was evaluated 0.5 hour after HISE. In addition, the effect of the fatty acid amide hydrolase [FAAH] inhibitor or monoacylglycerol lipase [MAGL] inhibitor on the antihyperalgesic action of HISE was investigated. HISE reduced mechanical hyperalgesia with effects prevented by AM281 or AM630 pretreatment in all delivery routes tested. The inhibition of FAAH and MAGL prolonged the antihyperalgesic effect of HISE. These data demonstrate evidence for the role of the eCB system upon exercise-induced analgesia in a murine model of inflammatory pain.
Abstract
Physical activity is an important lifestyle factor for growth, development, and sustained health throughout life. In recent years, the benefits of physical activity have drawn more attention to its physiological effects on the body, including well-being. The endocannabinoid system (ECS) has emerged as a focal point to ascertain the mechanisms for how exercise benefits the body and how it reduces or controls pain. The ECS, its ligands [the endocannabinoids (eCB)], receptors (CB1 and CB2), enzymes for the synthesis and degradation of eCB, and the polyunsaturated fatty acids (PUFA) that serve as substrates, comprise a powerful biological organization of multiple controls that affects mood, inflammation, pain, and other neurological aspects of the central nervous system and peripheral nervous system. Recently, investigators have reported increases in circulating levels of eCB after exercise, with some eCB exerting analgesic effects from exercise. The focus of this review is to discuss evidence for the role of eCB and the complexities of the ECS in exercise and pain. Some aspects presented herein are production of eCB and activation of the cannabinoid receptors in the brain following exercise; eCB, pain, and physical activity; oxylipins; and joint pain. Future research on the ECS must include mechanistic approaches to endocannabinoid signaling and explain the role of dietary PUFA in altering signaling of the receptors that affects pain. Additionally, how other types of exercise, such as Tai Chi, which is reported to improve well-being, should be investigated to ascertain if changes in eCB mediate the mind and body benefits of Tai Chi. As we age, exercise in the form of play has evolved with the exploration of our body from walking to running, recreational, and competitive sports, to midlife physical activity focusing on maintaining fitness and a healthy body weight. Furthermore, exercise has been a target of investigation to explore various hypotheses to explain the mechanisms for cognitive benefits in the young and in older adults. The science of exercise has matured to a level of importance in the life cycle to reduce pain with aging and include new investigations on the ECS to explain its role in well-being and improved quality of life in later years.
Abstract
Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward. Recent work shows that exercise activates the eCB system in humans and other mammals, suggesting eCBs are partly responsible for the reported improvements in mood and affect following aerobic exercise in humans. However, exercise-induced psychological changes reported by runners are known to be dependent on exercise intensity, suggesting that any underlying molecular mechanism should also change with varying levels of exercise intensity. Here, we examine circulating levels of eCBs following aerobic exercise (treadmill running) in recreationally fit human runners at four different intensities. We show that eCB signaling is indeed intensity dependent, with significant changes in circulating eCBs observed following moderate intensities only (very high and very low intensity exercises do not significantly alter circulating eCB levels). Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise. Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account.
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