Regular physical activity prevents chronic pain by altering resident muscle macrophage phenotype and increasing interleukin-10 in mice.
Regular physical activity prevents chronic pain by altering resident muscle macrophage phenotype and increasing interleukin-10 in mice.
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DOI：
10.1097/j.pain.0000000000000312
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发表时间：
2016-01
期刊：
影响因子：
7.4
通讯作者：
Sluka KA
中科院分区：
文献类型：
--
作者：
Leung A;Gregory NS;Allen LH;Sluka KA
健康人有规律的体力活动可以预防慢性肌肉骨骼疼痛的发展；然而，这种运动诱导的止痛机制还不是很清楚。白介素10(IL-10)是一种抗炎细胞因子，可以减少伤害性感受器的敏感化，在正常的体力活动中会增加。由于巨噬细胞在细胞因子的产生中起主要作用，并且存在于肌肉组织中，我们认为身体活动可以改变巨噬细胞的表型，从而增加IL-10并预防慢性疼痛。通过允许C57BL/6J小鼠自由使用跑轮8周来诱导体力活动，并与没有跑轮的久坐小鼠进行比较。用免疫组织化学染色标记调节性巨噬细胞(M2，分泌抗炎细胞因子)和经典巨噬细胞(M1，分泌促炎细胞因子)，发现运动组小鼠的M2-巨噬细胞百分比(68.5±4.6%)显著高于久坐组(45.8±7.1%)。在久坐不动的动物的肌肉和爪子中反复注射酸性物质会增强肌肉和爪子的机械敏感性，这在经常运动的小鼠中是不会发生的；无论是久坐不动的小鼠还是运动的小鼠，都没有性别差异。阻断IL-10可全身或局部阻断运动小鼠的镇痛作用，即小鼠出现痛觉过敏。相反，系统地或局部地用IL-10对久坐不动的小鼠进行治疗，可以减少反复注射酸后的痛觉过敏。因此，这些结果表明，有规律的体力活动增加了肌肉中调节性巨噬细胞的百分比，IL-10是由有规律的体力活动产生的止痛的重要中介。
Regular physical activity in healthy individuals prevents development of chronic musculoskeletal pain; however, the mechanisms underlying this exercise-induced analgesia are not well understood. Interleukin-10(IL-10), an anti-inflammatory cytokine which can reduce nociceptor sensitization, increases during regular physical activity. Since macrophages play a major role in cytokine production and are present in muscle tissue, we propose that physical activity alters macrophage phenotype to increase IL-10 and prevent chronic pain. Physical activity was induced by allowing C57BL/6J mice free access to running wheels for 8 weeks and compared to sedentary mice with no running wheels. Using immunohistochemical staining of the gastrocnemius muscle to label regulatory (M2, secretes anti-inflammatory cytokines) and classical (M1, secretes proinflammatory cytokines) macrophages, the percentage of M2-macrophages increased significantly in physically active mice (68.5±4.6% of total) compared to sedentary mice (45.8±7.1% of total). Repeated acid injections into the muscle enhanced mechanical sensitivity of the muscle and paw in sedentary animals that does not occur in physically active mice; no sex differences occur in either sedentary or physically active mice. Blockade of IL-10 systemically or locally prevented the analgesia in physically active mice, i.e. mice developed hyperalgesia. Conversely, sedentary mice pretreated systemically or locally with IL-10 had reduced hyperalgesia after repeated acid injections. Thus, these results suggest that regular physical activity increases the percentage of regulatory macrophages in muscle and that IL-10 is an essential mediator in the analgesia produced by regular physical activity.