Institute of Motricity Sciences, Federal University of Alfenas, Minas Gerais, Av. Jovino Fernandes Sales, 2600, 37133-840, Alfenas, Brazil.
Faculty of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Neuroscience. 2019 Oct 15;418:177-188. doi: 10.1016/j.neuroscience.2019.08.041. Epub 2019 Aug 29.
Muscle pain affects approximately 11-24% of the global population. Several studies have shown that exercise is a non-pharmacological therapy to pain control. It has been suggested that the endocannabinoid system is involved in this antinociceptive effect. However, the participation of this pathway is unclear. The present study aimed to investigate whether spinal cannabinoid CB receptors participate in the exercise-induced antinociception. The inflammatory muscle pain model was induced by the intramuscular injection of carrageenan. Tactile allodynia and thermal hyperalgesia were determined with the von Frey filaments and hot-plate tests. C57BL/6J female mice underwent a swimming training protocol that lasted 3 weeks. This protocol of exercise reduced carrageenan-induced tactile allodynia and thermal hyperalgesia and this effect was prevented by the cannabinoid CB receptors inverse agonist AM630 and potentiated by MAFP (inhibitor of the enzyme that metabolizes endocannabinoids) and minocycline (microglia inhibitor). In addition, exercise increased the endocannabinoid anandamide levels and cannabinoid CB receptors expression whereas it reduced Iba1 (microglial marker) protein expression as well as pro-inflammatory cytokines (TNF-α and IL-1β) in the spinal cord of mice with inflammatory muscle pain. Swimming training also reduced muscle temperature of carrageen-treated animals. The present study suggests that activation of spinal cannabinoid CB receptors and reduction of activated microglia are involved in exercise-induced antinociception.
肌肉疼痛影响全球约 11-24%的人口。多项研究表明，运动是一种控制疼痛的非药物疗法。有研究表明，内源性大麻素系统参与了这种镇痛作用。然而，这种途径的参与尚不清楚。本研究旨在探讨脊髓大麻素 CB 受体是否参与运动引起的镇痛作用。通过肌肉内注射卡拉胶诱导炎症性肌肉疼痛模型。使用 von Frey 纤维和热板试验测定触觉过敏和热痛觉过敏。C57BL/6J 雌性小鼠接受了为期 3 周的游泳训练方案。这种运动方案减轻了卡拉胶诱导的触觉过敏和热痛觉过敏，而大麻素 CB 受体反向激动剂 AM630 可预防这种作用，MAFP（内源性大麻素代谢酶抑制剂）和米诺环素（小胶质细胞抑制剂）则增强了这种作用。此外，运动增加了内源性大麻素大麻素的水平和 CB 受体的表达，同时减少了脊髓中 Iba1（小胶质细胞标志物）蛋白的表达以及促炎细胞因子（TNF-α 和 IL-1β）的表达在有炎症性肌肉疼痛的小鼠中。游泳训练还降低了卡拉胶处理动物的肌肉温度。本研究表明，脊髓大麻素 CB 受体的激活和激活的小胶质细胞的减少参与了运动引起的镇痛作用。
