P2X3 receptors contribute to muscle pain induced by static contraction by a mechanism dependent on neutrophil migration

Bruna de Melo Aquino, de Melo Aquino B, Diogo Francisco da Silva dos Santos, da Silva Dos Santos DF, Jorge CO, Carolina Ocanha Jorge, Aline Carolina Salgado Marques, Marques ACS, Juliana Maia Teixeira, Teixeira JM, Parada CA, Carlos Amilcar Parada, Oliveira-Fusaro MCG
Purinergic signalling · 2019 · vol. 15(2) , pp. 167–175 · doi:10.1007/s11302-019-09659-0 · PMID:31115830 · PMC6635523
Lab / animal OA: closed
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In rats, blocking P2X3 receptors prevented static contraction-induced muscle hyperalgesia and neutrophil migration without altering TNF-α or IL-1β levels, indicating these receptors mediate acute musculoskeletal pain development.

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Abstract

P2X3 receptors are involved with several pain conditions. Muscle pain induced by static contraction has an important socioeconomic impact. Here, we evaluated the involvement of P2X3 receptors on mechanical muscle hyperalgesia and neutrophil migration induced by static contraction in rats. Also, we evaluated whether static contraction would be able to increase muscle levels of TNF-α and IL-1β. Male Wistar rats were pretreated with the selective P2X3 receptor antagonist, A-317491, by intramuscular or intrathecal injection and the static contraction-induced mechanical muscle hyperalgesia was evaluated using the Randall-Selitto test. Neutrophil migration was evaluated by measurement of myeloperoxidase (MPO) kinetic-colorimetric assay and the cytokines TNF-α and IL-1β by enzyme-linked immunosorbent assay. Intramuscular or intrathecal pretreatment with A-317491 prevented static contraction-induced mechanical muscle hyperalgesia. In addition, A-317491 reduced static contraction-induced mechanical muscle hyperalgesia when administered 30 and 60 min of the beginning of static contraction, but not after 30 and 60 min of the end of static contraction. Intramuscular A-317491 also prevented static contraction-induced neutrophil migration. In a period of 24 h, static contraction did not increase muscle levels of TNF-α and IL-1β. These findings demonstrated that mechanical muscle hyperalgesia and neutrophil migration induced by static contraction are modulated by P2X3 receptors expressed on the gastrocnemius muscle and spinal cord dorsal horn. Also, we suggest that P2X3 receptors are important to the development but not to maintenance of muscle hyperalgesia. Therefore, P2X3 receptors can be pointed out as a target to musculoskeletal pain conditions induced by daily or work-related activities.

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MeSH descriptors

Myalgia Neutrophils Neutrophils Receptors, Purinergic P2X3 Animals Cell Movement Hyperalgesia Hyperalgesia Hyperalgesia Male Muscle Contraction Muscle Contraction Muscle Contraction Myalgia Myalgia Phenols Phenols Polycyclic Compounds Polycyclic Compounds Purinergic P2X Receptor Antagonists

Funding

funders
[{'doi': '10.13039/501100002322', 'name': 'Coordenação de Aperfeiçoamento de Pessoal de Nível Superior', 'awards': ['Finance Code 001']}, {'doi': '10.13039/501100002322', 'name': 'Coordenação de Aperfeiçoamento de Pessoal de Nível Superior', 'awards': ['Finance Code 001']}, {'doi': '10.13039/501100002322', 'name': 'Coordenação de Aperfeiçoamento de Pessoal de Nível Superior', 'awards': ['Finance Code 001']}, {'doi': '10.13039/501100001807', 'name': 'Fundação de Amparo à Pesquisa do Estado de São Paulo', 'awards': ['2011/11064-4']}, {'doi': '10.13039/501100001807', 'name': 'Fundação de Amparo à Pesquisa do Estado de São Paulo', 'awards': ['2012/10402-6']}, {'doi': '10.13039/501100001807', 'name': 'Fundação de Amparo à Pesquisa do Estado de São Paulo', 'awards': ['2013/23448-7']}]

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