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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    461—Descending Modulation: Anatomical and Physiological Studies

    Monday, November 11, 2013, 1:00 pm - 5:00 pm

    461.15: The endocannabinoid system mediates aerobic exercise-induced antinociception in rats

    Location: Halls B-H

    1Federal Univ. of Alfenas, Alfenas, Brazil; 2Federal Univ. of Minas Gerais, Belo Horizonte, Brazil; 3Endocannabinoid Res. Group, Napoli, Italy

    Abstract Body: Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB1 and CB2 cannabinoid receptors antagonists (AM251 and AM630) blocked antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Immunofluorescence and Western blot analysis revealed an increase and activation of CB1 cannabinoid receptors in rat brain, mainly in the periaqueductal gray matter (PAG), after exercise. In addition, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise may activate endocannabinoids system producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators, palmitoylethanolamide and oleoylethanolamide, were increased after AE. These results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels.

    Lay Language Summary: Our study indicates that physical exercise activates endocannabinoid system that consequently participates of analgesia induced by exercise.
    Worldwide, one in five people suffer from moderate to severe chronic pain, and one in three is unable or less able to conduct an independent lifestyle due to their pain. Thus, non-pharmacological strategies such as physical exercise have been well widely used as a potent therapeutic approach for pain treatment not only for providing relief from symptoms, but especially to reduce the financial burden and the side effects associated with chronic use of analgesic and anti-inflammatory medicine. Analgesia induced by exercise has been investigated since the early 80’s, but few substances have been shown to underlie this effect. In addition, substances produced in our body with effects similar to marijuana, called endocannabinoids, have received great attention, manly for producing analgesia. Our findings suggest that the endocannabinoids system is activated during exercise inducing analgesia. Recently, a study demonstrated that the endocannabinoid system may be activated by exercise, manly after found an increase in anandamide plasma (an endocannabinoid) levels in humans after running and cycling. In addition, these authors suggesting that this system could be involved in the exercise-induced analgesia. However, these authors did not assess the nociceptive threshold nor investigated the participation of cannabinoid receptors.
    To answer our hypothesis that endocannabinoids system is involved with analgesia induced by exercise, we used rats that were subjected to an exercise protocol in a rodent treadmill, until fatigue. The pain threshold was evaluated for mechanical and thermal stimulus and to investigate the involvement of endocannabinoid system, drugs that blocking and potentiating this system were administered before to exercise. Furthermore, was evaluated if the exercise produces increase of cannabinoid receptors in brain of rats and if the exercise alters the endocannabinoids levels in the plasma. The pain threshold was measured before and to exercise. The drugs were given before starting of exercise and the cannabinoids receptors in the brain of rats and the endocannabinoids plasma levels were evaluated after exercise.
    Aerobic exercise produced an increase of pain threshold, which lasted for 15 minutes. This effect was reversed for cannabinoids receptors blockers and prolonged (from 15 to 45 minutes) for enzymes degrading endocannabinoids blockers. Furthermore, after exercise, was also found an increase of number of cannabinoids receptors in brain of rats and of endocannabinoids in the plasma.
    Futures experiments will be conducted with cannabinoids receptors null-mutants mice and in humans to help clarify how these findings may be useful and applied to clinical practice. Additionally, this study may demonstrate that the activation of endocannabinoid system may useful to help not only in pain control, but also in several diseases.
    Thus, the present study indicates that a single session of aerobic exercise produces analgesia that is mediated for endocannabinoids releasing, which acts on cannabinoids receptors existing in different locations of our body. For example, brain and limbs. Furthermore, these results open the way to further investigations of the endocannabinoid system in exercise-induced therapies in individuals with different painful conditions, such as athletes or patients undergoing a rehabilitation program.