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
• Start date: May 01, 2019
• End date: 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

Abstract

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)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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, JUL 2021. (18/13599-1, 17/17919-8)

DE AZAMBUJA, GRACIANA; SIMABUCO, FERNANDO MOREIRA; DE OLIVEIRA, MARIA CLAUDIA GONCALVES. Macrophage-P2X4 receptors pathway is essential to persistent inflammatory muscle hyperalgesia onset, and is prevented by physical exercise. PLoS One, v. 20, n. 2, p. 20-pg., 2025-02-11. (18/13599-1, 21/02921-2, 20/10585-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AZAMBUJA, Graciana de. The chronic muscle pain prevention by physical exercise: The role of non-neuronal cells in the anti-inflammatory process. 2022. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.