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Regular physical activity prevents chronic pain by altering resident muscle macrophage phenotype and increasing interleukin-10 in mice
Journal article   Open access   Peer reviewed

Regular physical activity prevents chronic pain by altering resident muscle macrophage phenotype and increasing interleukin-10 in mice

Audrey Leung, Nicholas S Gregory, Lee-Ann H Allen and Kathleen A Sluka
Pain (Amsterdam), Vol.157(1), pp.70-79
01/2016
DOI: 10.1097/j.pain.0000000000000312
PMCID: PMC4685958
PMID: 26230740
url
http://doi.org/10.1097/j.pain.0000000000000312View
Open Access

Abstract

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 antiinflammatory cytokine that 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 antiinflammatory 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 with 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, which 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, ie, 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.
Hyperalgesia - chemically induced Chronic Pain - metabolism Motor Activity - physiology Macrophages - metabolism Animals Chronic Pain - prevention & control Hyperalgesia - metabolism Interleukin-10 - metabolism Muscle, Skeletal - metabolism Mice Chronic Pain - physiopathology Hyperalgesia - physiopathology

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