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Mol Pain. 2019 Jun 4:1744806919858797. doi: 10.1177/1744806919858797. [Epub ahead of print]

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

Author information

1
Tohoku University Graduate School of Medicine.
2
Tohoku Fukushi University.
3
Nihon Daigaku Shigakubu Daigakuin Shigaku Kenkyuka.
4
Tohoku University Graduate School of Biomedical Engineering.
5
JR Sendai Hospital.
6
Tohoku University Graduate School of Dentistry School of Dentistry.

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 (MWTs), 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, MWTs 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.

PMID:
31161887
DOI:
10.1177/1744806919858797

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