Abstract
Long non-coding RNAs (LncRNAs) have recently been reported to play a crucial role in neuropathic pain (NP) resulting from peripheral nerve injury. However, the underlying mechanisms are not fully elucidated. Here, we investigated the role and mechanism of lncRNA 4930544M13Rik-201, a significantly up-regulated lncRNA in both trigeminal ganglion (TG) and dorsal root ganglion (DRG) following peripheral nerve injury, as determined by previous RNA-sequencing results, in the pathogenesis of trigeminal NP induced by infraorbital nerve chronic constriction injury (CCI-ION) in mice. LncRNA 4930544M13Rik-201 was predominantly located in the nuclei of neurons and significantly upregulated in the TG after CCI-ION. Silencing the expression of 4930544M13Rik-201 alleviated mechanical allodynia induced by CCI-ION, while over-expression of 4930544M13Rik-201 in the TG of the WT mice caused orofacial allodynia. Moreover, calcium voltage-gated channel auxiliary subunit alpha 2 delta 1 (CACNA2D1) was identified as the downstream target of lncRNA 4930544M13Rik-201. Notably, 4930544M13Rik-201 increased the stabilization of Cacna2d1 mRNA and protein expression via interacting with heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1). Furthermore, inhibition of CACNA2D1 and silencing of hnRNPA2B1 both alleviated the allodynia induced by CCI-ION and the overexpression of 4930544M13Rik-201. Taken together, these results suggest that 4930544M13Rik-201 plays a critical role in the regulation of trigeminal NP induced by CCI-ION through upregulating Cacna2d1 expression via binding to hnRNPA2B1. These findings have important implications for the development of new therapeutic strategies for the treatment of NP by targeting the 4930544M13Rik-201—hnRNPA2B1—CACNA2D1 axis.