Details

Autor(en) / Beteiligte

• Tu, Chen
• Chen, Yun-Biao
• Lai, Si-Qi
• Yu, Yong-Peng
• Huang, Zhi-Wei
• Li, Hong-Zhou
• Ao, Rui-Feng
• Han, Dong
• Gao, Jia-Wen
• Zhu, Guo-Zheng
• Wu, Di-Zheng
• Huang, Yu-Sheng
• Zhao, Kai
• Meng, Ting-Ting
• Zhong, Zhao-Ming

Titel

Accumulation of β-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling

Ist Teil von

• Biochimica et biophysica acta. Molecular basis of disease, 2024-08, Vol.1870 (6), p.167269, Article 167269

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. β-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women. •Increased BAIBA levels associated with the development of hyperalgesia in ovariectomized (OVX) mice.•Reduced expression of AGXT2 and ABAT in OVX mice contributes to the elevation of BAIBA.•BAIBA enhances the excitability of DRG neurons via MrgprD.•MrgprD signaling is pivotal for BAIBA-induced hyperalgesia.