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Electroacupuncture decreases inflammatory pain through a pro-resolving mechanism involving the peripheral annexin A1-formyl peptide receptor 2/ALX-opioid receptor pathway

  • Neuroscience
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Abstract

The pro-resolving mechanism is a recently described endogenous process that controls inflammation. The present study evaluated components of this mechanism, including annexin 1 (ANXA1) and the formyl peptide receptor 2/ALX (FPR2/ALX) receptor, in the antihyperalgesic effect induced by electroacupuncture (EA) in an animal model of persistent peripheral inflammation. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund’s adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2–10 Hz, ST36-SP6) or subcutaneous BML-111 injection (FPR2/ALX agonist) for 5 consecutive days. In a separate set of experiments, on the first and fifth days after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or naloxone (non-selective opioid receptor antagonist) before EA or BML-111 injection. Paw protein levels of FPR2/ALX and ANXA1 were evaluated on the second day after CFA injection by western blotting technique. EA and BML-111 reduced mechanical hyperalgesia. I.pl. naloxone or WRW4 prevented the antihyperalgesic effect induced by either EA or BML-111. EA increased ANXA1 but did not alter FPR2/ALX receptor levels in the paw. Furthermore, i.pl. pretreatment with WRW4 prevented the increase of ANXA1 levels induced by EA. This work demonstrates that the EA antihyperalgesic effect on inflammatory pain involves the ANXA1/FPR2/ALX pro-resolution pathway. This effect appears to be triggered by the activation of FPR2/ALX receptors and crosstalk communication with the opioid system.

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Funding

This work was supported by grants from the National Council for Scientific and Technological Development (CNPq; grant number 430556/2018-7) and Foundation of Support for Research and Innovation of the State of Santa Catarina (FAPESC; grant number 2019TR73) and by the Coordination for the Higher Education (CAPES) and Unisul Scientific Initiation Program (PUIC), Brazil. DFM is supported by research fellowships from CNPq (309407/2017-6).

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  1. Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil

    Cintia Vieira, Daiana C. Salm, Verônica V. Horewicz, Daniela D. Ludtke, Aline A. Emer, Júlia F. Koerich, Gustavo Mazzardo, Sayron Elias, Leidiane Mazzardo-Martins, Francisco J. Cidral-Filho, Anna Paula Piovezan & Daniel F. Martins

  2. Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil

    Cintia Vieira, Daiana C. Salm, Verônica V. Horewicz, Daniela D. Ludtke, Aline A. Emer, Júlia F. Koerich, Francisco J. Cidral-Filho, Anna Paula Piovezan & Daniel F. Martins

  3. Postgraduate Program in Neuroscience, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Leidiane Mazzardo-Martins

  4. Integrative Medicine and Acupuncture Division, University Hospital, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Ari O. O. Moré

  5. Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA

    William R. Reed

  6. Rehabilitation Science Program, University of Alabama at Birmingham, Birmingham, AL, USA

    William R. Reed

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Vieira, C., Salm, D.C., Horewicz, V.V. et al. Electroacupuncture decreases inflammatory pain through a pro-resolving mechanism involving the peripheral annexin A1-formyl peptide receptor 2/ALX-opioid receptor pathway. Pflugers Arch - Eur J Physiol 473, 683–695 (2021). https://doi.org/10.1007/s00424-020-02502-1

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