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IL-10 Cytokine Released from M2 Macrophages Is Crucial for Analgesic and Anti-inflammatory Effects of Acupuncture in a Model of Inflammatory Muscle Pain

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Abstract

Muscle pain is a common medical problem that is difficult to treat. One nonpharmacological treatment used is acupuncture, a procedure in which fine needles are inserted into body points with the intent of relieving pain and other symptoms. Here we investigated the effects of manual acupuncture (MA) on modulating macrophage phenotype and interleukin-10 (IL-10) concentrations in animals with muscle inflammation. Carrageenan, injected in the gastrocnemius muscle of mice, induces an inflammatory response characterized by mechanical hyperalgesia and edema. The inflammation is initially a neutrophilic infiltration that converts to a macrophage-dominated inflammation by 48 h. MA of the Sanyinjiao or Spleen 6 (SP6) acupoint reduces nociceptive behaviors, heat, and mechanical hyperalgesia and enhanced escape/avoidance and the accompanying edema. SP6 MA increased muscle IL-10 levels and was ineffective in reducing pain behaviors and edema in IL-10 knockout (IL-10−/−) mice. Repeated daily treatments with SP6 MA induced a phenotypic switch of muscle macrophages with reduced M1 macrophages (pro-inflammatory cells) and an increase of M2 macrophages (anti-inflammatory cells and important IL-10 source). These findings provide new evidence that MA produces a phenotypic switch in macrophages and increases IL-10 concentrations in muscle to reduce pain and inflammation.

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Acknowledgments

This study was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Brazil. M.D. Silva, F. Bobinski, and A.R.S. Santos thank the CAPES (regular and by PhD exterior program—CsF) and CNPq, respectively, for their fellowship support. This study was funded in part by the National Institutes of Health grants AR061371 and AR053509 to K.A. Sluka.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil

    Morgana D. da Silva, Franciane Bobinski & Adair R. S. Santos

  2. Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil

    Morgana D. da Silva, Franciane Bobinski & Adair R. S. Santos

  3. Departamento de Fisioterapia, Universidade Federal do Pampa, Campus Universitário, BR 472, Km 92, Uruguaiana, RS, 97500-970, Brazil

    Morgana D. da Silva

  4. Department of Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, #1-252 MEB, Iowa, IA, 52241, USA

    Karina L. Sato, Sandra J. Kolker & Kathleen A. Sluka

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  1. Morgana D. da Silva
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  2. Franciane Bobinski
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  3. Karina L. Sato
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  6. Adair R. S. Santos
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Correspondence to Adair R. S. Santos.

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da Silva, M.D., Bobinski, F., Sato, K.L. et al. IL-10 Cytokine Released from M2 Macrophages Is Crucial for Analgesic and Anti-inflammatory Effects of Acupuncture in a Model of Inflammatory Muscle Pain. Mol Neurobiol 51, 19–31 (2015). https://doi.org/10.1007/s12035-014-8790-x

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