Dexmedetomidine alleviates anxiety-like behaviors in female mice with musculoskeletal pain through SIRT1/p53 axis

Abstract

Background: Musculoskeletal pain is the most common form of chronic pain. Anxiety increases pain intensity and appears to have a major impact on the prevalence and also disability of musculoskeletal pain in women. We examined the effect of dexmedetomidine (DEX) on anxiety-like behaviors associated with musculoskeletal pain and the underlying molecular mechanism in female mice. Methods: Musculoskeletal pain was induced by injection of acidified saline into the gastrocnemius muscle in adult female mice, and the von Frey filament test is used to measure mechanical sensitivity. DEX and EX527 (SIRT1 inhibitor) were administered after modelling. Behavioral tests were used for anxiety and motor activity tests. SIRT1, p53 and acetyl-p53 were quantified by Western blot. Results: Adult female mice with musculoskeletal pain exhibit increased fear-like behavior by reducing SIRT1 expression in the medial prefrontal cortex (mPFC). While administration of DEX was able to alleviate mechanical hypersensitivity and anxiety-like behaviors by blocking SIRT1 decline and acetyl-p53 upregulation in mPFC, EX527 inhibited acetyl-p53 rise and reversed the antinociceptive and anxiolytic effects of DEX. Conclusion: DEX may alleviate anxiety-like behaviors in mice with musculoskeletal pain via the SIRT1/p53 axis. These results suggest that DEX may have a potential therapeutic role in musculoskeletal pain-induced anxiety.

Keywords

• Dexmedetomidine
• Musculoskeletal pain
• Anxiety
• SIRT1/p53 axis
• Female