Background: The participation of long non-coding RNAs (lncRNAs) in progressions of chronic pain has been evaluated. We explored mechanisms of lncRNA H19 in chronic constriction injury (CCI)-induced neuropathic pain model in vivo.

Methods: The expressions of lncRNA H19, microRNA-141, and GLI Family Zinc Finger 2 (GLI2) in CCI rats were determined by using RT-qPCR. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used as neuropathic pain index implying mechanical allodynia and thermal hyperalgesia. The protein concentrations of IL-1β, IL-6 and TNF-α in rats were examined by ELISA assay. RT-qPCR analyzed gene expression changes of lncRNA H19, miR-141 and GLI2. Online bioinformatics predictions supported that the bindings between miR-141 and GLI2 and dual luciferase reporter method, and RNA pull-down assays determined connections within lncRNA H19, miR-141 and GLI2 in HEK 293 cells.

Results: LncRNA H19 was upregulated in the tissues of rats. Also, thermal hyperalgesia and mechanical allodynia were inhibited by lncRNA H19 suppression in rats. Moreover, IL-1β, IL-6 and TNF-α protein concentrations were suppressed by the downregulation of lncRNA H19 in rats. Furthermore, miR-141 was reduced in CCI rats and restored by the lncRNA H19 knockdown, suggesting the potential negative associations of miR-141 with lncRNA H19. GLI2 targeted miR-141 and GLI2 was increased in CCI rats. Additionally, the neuropathic pain was inhibited by the inhibition of GLI2 in rats, which was reversed by the miR-141 inhibitors.

Conclusion: LncRNA H19 aggravated the neuropathic pain of CCI rats through miR-141/GLI2 axis, implying that lncRNA H19 might be a biomarker for the inflammation-related neuropathic pain.