P2X4 Receptors on Muscle Macrophages Are Required for Development of Hyperalgesia in an Animal Model of Activity-Induced Muscle Pain

Autor(es)

Oliveira-Fusaro, Maria Claudia ^[1] ; Gregory, Nicholas S. ^[2] ; Kolker, Sandra J. ^[2] ; Rasmussen, Lynn ^[2] ; Allen, Lee-Ann H. ^{[3, 4]} ; Sluka, Kathleen A. ^[2]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Sch Appl Sci, BR-13484350 Limeira - Brazil

^[2] Univ Iowa, Dept Phys Therapy & Rehabil Sci, Neurosci Grad Program, Pain Res Program, Iowa City, IA 52242 - USA

^[3] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 - USA

^[4] Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA 52242 - USA

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 57, n. 4 JAN 2020.
• Citações Web of Science: 0

Resumo

Activity-induced pain is common in those with chronic musculoskeletal pain and limits participation in daily activities and exercise. Our laboratory developed a model of activity-induced pain and shows that depletion of muscle macrophages prevents development of hyperalgesia. Adenosine triphosphate (ATP) is released from fatiguing muscle and activates purinergic receptors (P2X), and P2X4 receptors are expressed on macrophages. We hypothesized that exercise releases ATP to activate P2X4 receptors on muscle macrophages, which subsequently release interleukin-1 beta (IL-1 beta) to produce hyperalgesia. In an animal model of activity-induced pain, using male and female C57BL6/J mice, we show increased expression of P2X4 on muscle macrophages, and blockade of P2X4 receptors in muscle prevented development of hyperalgesia. Using a lentivirus expressing an artificial micro-RNA to P2X4 under the control of a CD68 promoter, we decreased expression of P2X4 mRNA in cultured macrophages, decreased expression of P2X4 protein in muscle macrophages in vivo, and prevented development of activity-induced hyperalgesia. We further show that macrophages primed with LPS differentially released IL-1 beta when treated with ATP in neutral or acidic pH. Lastly, blockade of IL-1 beta in muscle prevented development of hyperalgesia in this model. Thus, our data suggest that P2X4 receptors could be a valid pharmacological target to control activity-induced muscle pain experienced by patients with chronic musculoskeletal pain. (AU)

• Processo FAPESP: 14/01119-4 - Papel dos receptores P2x4 no aumento da dor muscular induzido pelo exercício físico fatigante
• Beneficiário: Maria Cláudia Gonçalves de Oliveira
• Modalidade de apoio: Bolsas no Exterior - Pesquisa