Involvement of inflammasome activation via elevation of uric acid level in nociception in a mouse model of muscle pain

Shinichirou Yoshida, Yoshihiro Hagiwara, Masahiro Tsuchiya, Masamichi Shinoda, Masashi Koide, Hiroyasu Hatakeyama, Chayanit Chaweewannakorn, Kazuaki Suzuki, Toshihisa Yano, Yasuhito Sogi, Nobuyuki Itaya, Takuya Sekiguchi, Yutaka Yabe, Keiichi Sasaki, Makoto Kanzaki, Eiji Itoi

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Abstract

Muscle pain is a common condition in many diseases and is induced by muscle overuse. Muscle overuse induces an increase in uric acid, which stimulates the nucleotide-binding oligomerization domain-like receptor (NLR). This receptor contains the pyrin domain NLRP-3 inflammasome which when activated, results in the secretion of potent pro-inflammatory cytokines such as interleukin-1β (IL-1β). The aim of this study was to investigate the involvement of inflammasome activation via the elevation of uric acid level in nociception in a mouse model of muscle pain. The right hind leg muscles of BALB/c mice were stimulated electrically to induce excessive muscle contraction. The left hind leg muscles were not stimulated as a control. Mechanical withdrawal thresholds, levels of uric acid, IL-1β, and NLRP3, caspase-1 activity, and the number of macrophages were investigated. Furthermore, the effects of xanthine oxidase inhibitors, such as Brilliant Blue G, caspase-1 inhibitor, and clodronate liposome, on pain were investigated. In the stimulated muscles, mechanical withdrawal thresholds decreased, and the levels of uric acid, NLRP3, and IL-1β, caspase-1 activity, and the number of macrophages increased compared to that in the non-stimulated muscles. Administration of the inhibitors attenuated hyperalgesia caused by excessive muscle contraction. These results suggested that IL-1β secretion and NLRP3 inflammasome activation in macrophages produced mechanical hyperalgesia by elevating uric acid level, and xanthine oxidase inhibitors may potentially reduce over-exercised muscle pain.

Original languageEnglish
JournalMolecular Pain
Volume15
DOIs
Publication statusPublished - 2019 Jul 1

Keywords

  • Muscle pain
  • electrical stimulation
  • inflammasome
  • mechanical hyperalgesia
  • uric acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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    Yoshida, S., Hagiwara, Y., Tsuchiya, M., Shinoda, M., Koide, M., Hatakeyama, H., Chaweewannakorn, C., Suzuki, K., Yano, T., Sogi, Y., Itaya, N., Sekiguchi, T., Yabe, Y., Sasaki, K., Kanzaki, M., & Itoi, E. (2019). Involvement of inflammasome activation via elevation of uric acid level in nociception in a mouse model of muscle pain. Molecular Pain, 15. https://doi.org/10.1177/1744806919858797