Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.63231/2595-0118.e202553-pt
Brazilian Journal of Pain
Original Article

O ciclo estral modula a hiperalgesia muscular inflamatória aguda e persistente em fêmeas sedentárias, mas não exercitadas

Estrous cycle modulates the acute and persistent inflammatory muscle hyperalgesia in sedentary but not in exercised female mice

Hayla Lourenço Rodrigues; Beatriz Botasso Gomes; Graciana de Azambuja; Maria Cláudia Gonçalves de Oliveira

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Resumo

JUSTIFICATIVA E OBJETIVOS: Dor persistente é um problema de saúde pública que impacta significativamente a qualidade de vida. Mulheres relatam sentir dores persistentes com maior intensidade e frequência do que homens, o que é atribuído às flutuações dos hormônios sexuais. Neste estudo, investigou-se a influência do ciclo estral no desenvolvimento e manutenção da hiperalgesia muscular inflamatória aguda e persistente em fêmeas sedentárias e exercitadas.

MÉTODOS: A hiperalgesia muscular mecânica foi avaliada em camundongos fêmeas, da linhagem Swiss, submetidos ao modelo de hiperalgesia muscular inflamatória aguda e persistente, durante as quatro fases do ciclo estral (proestro, estro, metaestro ou diestro). O exercício foi realizado através da natação previamente à indução da hiperalgesia muscular.

RESULTADOS: Quando o estímulo inflamatório da carragenina ocorre na fase proestro, desencadeia-se a hiperalgesia muscular aguda de maior intensidade. Por outro lado, durante a fase estro, o estímulo inflamatório desencadeia a hiperalgesia muscular persistente de maior intensidade. A duração da hiperalgesia muscular persistente não é modulada pelos ciclos estrais. Exercícios de natação regulares preveniram a hiperalgesia muscular aguda e persistente independentemente do ciclo estral.

CONCLUSÃO: A fase do ciclo estral em que ocorreu o estímulo inflamatório é determinante para o desenvolvimento da hiperalgesia muscular aguda e sua transição para a fase persistente. Esse efeito foi observado em fêmeas sedentárias, mas não em exercitadas, sugerindo que a atividade física regular pode promover benefícios analgésicos independentemente da fase do ciclo estral ou das flutuações hormonais associadas. Pesquisas adicionais são necessárias para elucidar os mecanismos subjacentes ao desenvolvimento da hiperalgesia muscular inflamatória em fêmeas.

Palavras-chave

Camundongos fêmeas, Ciclo estral, Exercício físico, Hiperalgesia persistente, Músculo

Abstract

BACKGROUND AND OBJECTIVES: Persistent pain is a significant public health issue, profoundly impacting quality of life. Women experience persistent pain more frequently and with greater intensity than men, which is attributed to sexual hormonal fluctuations. This study investigated the influence of the estrous cycle on the development and maintenance of acute and persistent inflammatory muscle hyperalgesia in sedentary and exercised female mice.

METHODS: The study analyzed mechanical muscle hyperalgesia in female Swiss mice that underwent a model of acute and persistent inflammatory muscle hyperalgesia, during each of the four estrous cycle phases (proestrus, estrus, metestrus or diestrus). Swimming exercises were performed before the induction of acute and persistent inflammatory muscle hyperalgesia.

RESULTS: The inflammatory stimulus of carrageenan during the proestrus phase induced the most intense acute muscle hyperalgesia. Conversely, in the estrus phase, the inflammatory stimulus induced the most intense persistent muscle hyperalgesia. The maintenance of persistent muscle hyperalgesia was not modulated by estrous cycle. Regular swimming exercise prevented the acute and persistent muscle hyperalgesia, regardless of the estrous cycle.

CONCLUSION: These findings suggest that the estrous cycle phase during which an inflammatory insult occurs is critical for the development of acute inflammatory muscle hyperalgesia and its transition to the persistent phase. This effect was observed in sedentary, but not in exercised female mice, suggesting that regular physical activity may provide analgesic benefits regardless estrous cycle phase or the associated fluctuations in gender hormones. Further research is necessary to elucidate the mechanisms underlying the development of inflammatory muscle pain in females.
 

Keywords

Estrous cycle, Female mice, Persistent hyperalgesia, Physical exercise, Muscle

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Submitted date:
07/15/2025

Accepted date:
08/30/2025

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