Neuropathic pain is a severe disease caused by lesions or diseases in the somatosensory system. Long non-coding RNAs (lncRNAs) are important in the development and maintenance of neuropathic pain. However, the precise role of lncRNAs in regulating neuropathic pain remains largely unknown. In this study, a rat model of bilateral chronic constriction injury (bCCI) was established, and microarray was applied to analyze differentially expressed lncRNAs among sham group, bCCI group and the experimental group (bCCI rats administrated with a specific STAT3 inhibitor WP1066). Linc00311 and lncRNA-AK141205 were uncharacterized lncRNAs both upregulated by > 2 folds in bCCI model compared with Sham group, and they were ... More
Neuropathic pain is a severe disease caused by lesions or diseases in the somatosensory system. Long non-coding RNAs (lncRNAs) are important in the development and maintenance of neuropathic pain. However, the precise role of lncRNAs in regulating neuropathic pain remains largely unknown. In this study, a rat model of bilateral chronic constriction injury (bCCI) was established, and microarray was applied to analyze differentially expressed lncRNAs among sham group, bCCI group and the experimental group (bCCI rats administrated with a specific STAT3 inhibitor WP1066). Linc00311 and lncRNA-AK141205 were uncharacterized lncRNAs both upregulated by > 2 folds in bCCI model compared with Sham group, and they were downregulated by > 2 folds following WP1066 administration compared with bCCI group. Downregulation of linc00311 and lncRNA-AK141205 by specific siRNAs significantly attenuated mechanical allodynia, thermal and cold hyperalgesia in bCCI rats. In addition, inhibition of linc00311 and lncRNA-AK141205 inactivated the signal transducer and activator of transcription 3 (STAT3) signaling in spinal microglia in vivo and in vitro. Inhibition of linc00311 and lncRNA-AK141205 could reduce activation of STAT3 and production of proinflammatory cytokines. Moreover, activating STAT3 with SD19 could antagonize the effect of the suppressive effect of siRNAs on production of proinflammatory cytokines. Hence, it is likely that silencing linc00311 and lncRNA-AK141205 may be a promising and novel treatment for neuropathic pain.,Copyright © 2019 Elsevier B.V. All rights reserved.