Acute physical exercise promotes peripheral analgesia by activation of the opioidergic system in mice with diabetic peripheral neuropathy (DPN)

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Universidade Federal de Minas Gerais

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Background: Diabetes induced hyperalgesia is a complication of diabetes that is prevalent in the population and that directly reduces the life quality of patients. The management of pain symptoms is difficult to control, leading researchers to investigate new interventions and alternative strategies of treatment. Few studies have investigated the peripheral endogenous pain modulation role of the opioid system in progressive-maximal physical exercise as a candidate therapeutic control agent of diabetes induced hyperalgesia. Methods: sixteen Swiss mice were divided into the following 4 groups: Group A, Control Saline (SC) n=4; Group B, control naloxone (CN) n=4; Group C, HFD saline (HFDS) n=4; and Group D, HFD naloxone (HFDN) n=4. All mice exercised on a treadmill for 30 minutes at a speed of 5 meters per minute (m/min) to become familiarized with the protocol. The animals were then submitted to a progressive-maximal exercise protocol until fatigue, with speed increases of 1 m/min every 3 minutes until they reached fatigue. To evaluate peripheral hyperalgesia, paw withdrawal under pressure method was used as adapted to mice. An evaluation of opioid system activation was assessed by intraplantar injections of naloxone, a non-selective antagonist of opioid receptors, at a dose of 100 μg/paw. Results: the high-fat diet was able to induce increases in body weight (p = 0,0166) and adiposity (p <0,0001) and was effective in the induction of insulin resistance (*p=0,0018) and glucose tolerance (p=0,0065) in obese mice. After the 12th week, the mice showed reductions in the basal nociceptive threshold in a mechanical sensibility test (p=0,0322) and progressive-maximal physical exercise induced antihyperalgesia, which was reverted by an intraplantar injection of 100 µg naloxone in a mechanical sensitivity test (p=0,0003), demonstrating activation of the endogenous opioid system induced acutely by physical exercise in the exercise protocol used in this work (p<0,0001). Conclusion: a progressive-maximal exercise protocol until fatigue induces analgesia and modulates, via the opioid system, diabetes induced hyperalgesia in Swiss mice treated with a high-fat diet.

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Educação Física, Exercícios aeróbicos, Opióides, Neuropatia, Nervos periféricos, Diabetes, Analgesia, Hiperalgesia

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Neuropatia diabética, Diabetes Mellitus, Analgesia endógena, Exercício Físico

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