Study of preventive and therapeutic effects of physical exercise on hyperalgesia induced by social defeat stress in mice and associated neuroplastic mechanisms.

Abstract

Despite the pain is not one of the symptoms of depression, epidemiological studies indicate a close association and comorbidity between depressive disorder and chronic pain. Accordingly, several clinical and biological characteristics are shared between pain and depression; and several neuroanatomical structures, neural circuits and neurotransmitter systems have similar changes in these two conditions. In chronic diseases it is commonly observed an interaction between genetic predisposition and environmental events or circumstances determining its development. Among the environmental events, chronic stress appears to be a crucial factor for the development of depression; being also associated with chronic pain conditions. Studies have shown that both for depressive-like behaviors as for those associated with chronic pain, neuroplastic changes must occur in several Nervous System structures. One of the structures that has received increasing attention is the mesolimbic dopamine system, whose physiology may be affected by chronic stress conditions resulting in maladaptive neuroplastic changes that contribute to the establishment of disorders associated with depression and chronic pain. In view of the diverse and complex relationships between stress, depression and pain in general, there is great scientific interest in further study on this issue, as these are scarce. Another interesting aspect that suggest the occurrence of common neurophysiological mechanisms of chronic pain and depression is the fact that the most effective drugs for the treatment of various chronic pain conditions are antidepressants. Also, another approach with obvious effects both anti-hyperalgesic as antidepressants is physical exercise. In fact, the exercise has been increasingly indicated as non-pharmacological clinical intervention for the relief of symptoms in chronic pain conditions; similarly extensive research supports that physical exercise can reduce the incidence and severity of depression. Although the physiological mechanisms by which exercise produces its antidepressant effects are not yet fully understood, several animal studies show that physical activity promotes physiological effects similar to those promoted by antidepressant drugs mainly involving neuroplasticity phenomena in the hippocampal formation. On the other hand, are indeed rare the studies on the physiological mechanisms underlying the anti-hyperalgesic effect of physical exercise. In this context, it is noteworthy that there are no reports in the literature about the effects of physical exercise on neuroplasticity phenomena in the mesolimbic dopamine system in the context of depression and chronic pain either. Therefore, this project proposes to investigate the interrelationships between social chronic stress and the modulation of the mechanisms involved in nociceptive sensitivity as well as in pain chronification processes in an animal model. In addition, we intend to investigate the modulatory effect of exercise on this topic because, although modern pharmacological resources offer some relief in symptoms of chronic pain and depression, drugs used have limited effectiveness and significant side effects, making it imperative to conduct studies that will support the development of innovative non-pharmacological treatment strategies. The proposed study will also address neuroplasticity mechanisms in the mesolimbic dopamine system mediated mainly by the action of Brain Derived Neurotrophic Factor (BDNF) that may underlie the behavioral phenomena investigated (AU)