LncRNA 4930544M13Rik-201 regulates CACNA2D1 expression via interacting with hnRNPA2B1 to promote neuropathic pain following nerve injury.

Long non-coding RNAs (lncRNAs) have recently been reported to play a crucial role in neuropathic pain (NP). However, whether lncRNA 4930544M13Rik-201, a significantly up-regulated lncRNA in peripheral ganglia following nerve injury, contributes to NP is not elucidated. This study aimed to investigate the role and mechanism of 4930544M13Rik-201 in NP. In the current study, the head withdrawal threshold (HWT) of mice following infraorbital nerve chronic constriction injury (CCI-ION) was assessed using behavioral tests to evaluate the presence of neuropathic pain. To elucidate the underlying mechanisms, RT-qPCR, western blotting, RNA pull-down, RNA immunoprecipitation, immunofluorescence, and fluorescence in situ hybridization were performed. It was found that 4930544M13Rik-201 was predominantly located in the nuclei of neurons in the trigeminal ganglion (TG). Silencing 4930544M13Rik-201 alleviated mechanical allodynia, while overexpression of 4930544M13Rik-201 in the wild-type mice caused orofacial allodynia. Notably, 4930544M13Rik-201 increased the stabilization of calcium voltage-gated channel auxiliary subunit alpha 2 delta 1 (Cacna2d1) mRNA and protein expression via interacting with heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1). Furthermore, inhibition of CACNA2D1 and silencing of hnRNPA2B1 alleviated the allodynia and expression of 4930544M13Rik-201. In conclusion, these results suggest that 4930544M13Rik-201 promotes NP by upregulating Cacna2d1 expression via binding to hnRNPA2B1 following nerve injury.