Dexmedetomidine alleviates anxiety-like behaviors in female mice with musculoskeletal pain through SIRT1/p53 axis.
Anxiety
Dexmedetomidine
Female
Musculoskeletal pain
SIRT1/p53 axis
Journal
Brain research bulletin
ISSN: 1873-2747
Titre abrégé: Brain Res Bull
Pays: United States
ID NLM: 7605818
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
04
04
2023
revised:
25
06
2023
accepted:
02
07
2023
medline:
21
8
2023
pubmed:
6
7
2023
entrez:
5
7
2023
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 37406884
pii: S0361-9230(23)00123-5
doi: 10.1016/j.brainresbull.2023.110698
pii:
doi:
Substances chimiques
Dexmedetomidine
67VB76HONO
Tumor Suppressor Protein p53
0
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110698Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The corresponding author confirms on behalf of all authors that there have been no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated: The authors declare that they have no conflicts of interest.