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Inflammatory mechanisms underlying muscle pain chronification and its prevention by physical exercise: study of macrophages, PPAR gamma and P2X4 receptors involvment

Grant number: 18/13599-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2019
Effective date (End): September 30, 2022
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Maria Cláudia Gonçalves de Oliveira
Grantee:Graciana de Azambuja
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Associated scholarship(s):20/10585-0 - Investigation of a crosstalk pathway between skeletal muscle and sensory neurons: effects of physical exercise-induced PGC-1a1 in skeletal muscle on dorsal roots ganglion activation and metabolism, BE.EP.DR


Chronic musculoskeletal pain is a worldwide public health problem with important socioeconomic impact. Nowadays, different modulatory mechanisms of acute muscular pain are already known. However, little is known about the mechanisms underlying the transition from acute pain to chronic as well as its maintenance. In chronic pain conditions, pharmacological therapy is not always efficient, either because of the refractoriness of some patients or because of the numerous side effects. On the other hand, physical exercise has been evidenced as a very efficient therapeutic approach and without the side effects of pharmacological therapy. First experiments from our lab demonstrated that physical exercise not only reduces acute muscle pain but also prevents chronification. In addition, we have demonstrated that PPAR-³ receptors are involved in the prevention of acute muscle pain by physical exercise. Considering the clinical relevance of chronic muscular pain, the objective of the present study is to investigate the inflammatory mechanisms underlying the chronicity of muscular pain and to evaluate if these same mechanisms modulate the prevention of chronic muscular pain by physical exercise. The involvement of PPAR-gamma and P2X4 receptors, macrophages with M1/M2 phenotypes, pro and anti-inflammatory cytokines and induced nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) enzymes will be evaluated. For this, we will use a model of persistent muscle pain, which differentiates the stages of acute pain, chronicity and persistence of pain, physical exercise through swimming, behavioral pharmacology and techniques of molecular biology. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE AZAMBUJA, GRACIANA; JORGE, CAROLINA O.; GOMES, BEATRIZ B.; LOURENCO, HAYLA R.; SIMABUCO, FERNANDO M.; OLIVEIRA-FUSARO, MARIA CLAUDIA G.. Regular swimming exercise prevented the acute and persistent mechanical muscle hyperalgesia by modulation of macrophages phenotypes and inflammatory cytokines via PPAR gamma receptors. BRAIN BEHAVIOR AND IMMUNITY, v. 95, p. 462-476, . (18/13599-1, 17/17919-8)

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