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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This work was financially supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and by the Sao Paulo Research Foundation (FAPESP) (grant number 2011/11064-4; 2013/23448-7; 2012/10402-6).
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Male albino Wistar rats (200–250 g) from CEMIB (Multidisciplinary Center for Biological Research) UNICAMP were used and all the procedures followed the guidelines on using laboratory animals from IASP [34] and approved by the Committee on Animal Research of the State University of Campinas (license number 2448-1).
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de Melo Aquino, B., da Silva dos Santos, D.F., Jorge, C.O. et al. P2X3 receptors contribute to muscle pain induced by static contraction by a mechanism dependent on neutrophil migration. Purinergic Signalling 15, 167–175 (2019). https://doi.org/10.1007/s11302-019-09659-0
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DOI: https://doi.org/10.1007/s11302-019-09659-0