Macrophage-P2X4 receptors pathway is essential to persistent inflammatory muscle hyperalgesia onset, and is prevented by physical exercise

Autor(es)

de Azambuja, Graciana ; Simabuco, Fernando Moreira ; de Oliveira, Maria Claudia Goncalves

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 20, n. 2, p. 20-pg., 2025-02-11.

Resumo

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)

• Processo FAPESP: 18/13599-1 - Mecanismos inflamatórios subjacentes à cronicidade da dor muscular e a sua prevenção pelo exercício físico: estudo do envolvimento de macrófagos, receptores PPAR gama e P2X4
• Beneficiário: Graciana de Azambuja
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 21/02921-2 - Dor crônica e sua prevenção pelo exercício físico: mecanismos de sinalização celular envolvendo sistema muscular, imunológico e nervoso
• Beneficiário: Maria Cláudia Gonçalves de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/10585-0 - Investigação o crosstalk entre músculo esquelético e neurônios sensoriais: efeitos do PGC-1a1 induzido pelo exercício físico no músculo esquelético na ativação e metabolismo de gânglios das raízes dorsais
• Beneficiário: Graciana de Azambuja
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado