Involvement of Spinal Neuroplastin 65 in Neuropathic Pain by GABAA Receptor α2 Subunit Regulation
Li Xu, Yu Wang, Yang Jiao, Yulin Huang, Rui Xu, Xiaoping Gu, Wei Zhang, Zhengliang Ma- Anesthesiology and Pain Medicine
BACKGROUND:
Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2.
METHODS:
A chronic constrictive injury (CCI) pain model was established in male Sprague-Dawley rats to verify the change in spinal NP65 expression. Alterations in pain behavior and GABAAR-α2 protein expression were observed after intrathecal injection of NP65 overexpressing adeno-associated virus (AAV) in CCI rats. In vitro investigations on Neuroblastoma 2a cells, the effect of NP65 on GABAAR-α2 expression via the calcineurin-nuclear factor of activated T-cell 4 (CaN-NFATc4) signaling pathway was evaluated by manipulating NP65 expression.
RESULTS:
The expression level of NP65 protein and mRNA in the CCI group were significantly decreased (
CONCLUSIONS:
NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may serve as the underlying mechanism of NP.