| Full text | |
| Author(s): |
de Azambuja, Graciana
;
Simabuco, Fernando Moreira
;
de Oliveira, Maria Claudia Goncalves
Total Authors: 3
|
| Document type: | Journal article |
| Source: | PLoS One; v. 20, n. 2, p. 20-pg., 2025-02-11. |
| Abstract | |
Peripheral inflammation may lead to severe inflammatory painful conditions. Macrophages are critical for inflammation; modulating related pathways could be an essential therapeutic strategy for chronic pain diseases. Here we hypothesized that 1) Macrophage-P2X4 receptors are involved in the transition from acute to persistent inflammatory muscle hyperalgesia and that 2) P2X4 activation triggers a pro-inflammatory phenotype leading to Interleukin-1 beta (IL-1 beta) increase. Once physical exercise prevents exacerbated inflammatory processes related to chronic diseases including chronic muscle pain, we also hypothesized that 3) physical exercise, through PPAR gamma receptors, prevents P2X4 receptors activation. With pharmacological behaviour, biomolecular analysis and swimming physical exercise in a mouse model of persistent inflammatory muscle hyperalgesia we demonstrated that P2X4 receptors are essential for transitioning from acute to persistent inflammatory muscle hyperalgesia; Phosphorylation of p38MAPK indicated P2X4 signalling activation associated with inflammatory macrophage and an increase of IL-1 beta expression in skeletal muscle; Exercise-PPAR gamma receptors prevented phosphorylation of p38MAPK in muscle tissue. Our findings suggest that exercise-PPAR gamma modulates the acute inflammatory phase of developing persistent muscle hyperalgesia by controlling p38MAPK-related P2X4 signalling. These highlight the great potential of modulating macrophage phenotypes and P2X4 receptors to prevent pain conditions and the ability of physical exercise to prevent inflammatory processes related to chronic muscle pain. (AU) | |
| FAPESP's process: | 18/13599-1 - Inflammatory mechanisms underlying muscle pain chronification and its prevention by physical exercise: study of macrophages, PPAR gamma and P2X4 receptors involvment |
| Grantee: | Graciana de Azambuja |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 21/02921-2 - Chronic pain and its prevention by physical exercise: cellular signaling mechanisms involving muscular, immunological and nervous system |
| Grantee: | Maria Cláudia Gonçalves de Oliveira |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 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 |
| Grantee: | Graciana de Azambuja |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |