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

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 electroacupunc...

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Published in:	Pflügers Archiv Vol. 473; no. 4; pp. 683 - 695
Main Authors:	Vieira, Cintia, Salm, Daiana C., Horewicz, Verônica V., Ludtke, Daniela D., Emer, Aline A., Koerich, Júlia F., Mazzardo, Gustavo, Elias, Sayron, Moré, Ari O. O., Mazzardo-Martins, Leidiane, Cidral-Filho, Francisco J., Reed, William R., Piovezan, Anna Paula, Martins, Daniel F.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2021 Springer Nature B.V
Subjects:	Acupuncture Animal models Animals Annexin A1 - metabolism Biomedical and Life Sciences Biomedicine Cell Biology Electroacupuncture Electroacupuncture - methods Freund's Adjuvant - toxicity Heptanoic Acids - pharmacology Human Physiology Hyperalgesia Hyperalgesia - etiology Hyperalgesia - metabolism Hyperalgesia - therapy Inflammation Injection Male Mice Molecular Medicine Naloxone Naloxone - pharmacology Narcotic Antagonists - pharmacology Narcotics Neuroscience Neurosciences Nociception - drug effects Nociceptive Pain - etiology Nociceptive Pain - metabolism Nociceptive Pain - therapy Opioid receptors Pain perception Peptides Receptors Receptors, Formyl Peptide - antagonists & inhibitors Receptors, Formyl Peptide - metabolism Receptors, Opioid - metabolism Receptors, Opioid - therapeutic use Western blotting FPR2/ALX Mice Pain Annexin A1 Electroacupuncture
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0031-6768 1432-2013
DOI:	10.1007/s00424-020-02502-1