title: A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons.
abstract: Neuropathic pain is a refractory disease characterized by maladaptive changes in gene transcription and translation in the sensory pathway. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the development of neuropathic pain is unclear. Here we identify a conserved lncRNA, named Kcna2 antisense RNA, for a voltage-dependent potassium channel mRNA, Kcna2, in first-order sensory neurons of rat dorsal root ganglion (DRG). Peripheral nerve injury increased Kcna2 antisense RNA expression in injured DRG through activation of myeloid zinc finger protein 1, a transcription factor that binds to the Kcna2 antisense RNA gene promoter. Mimicking this increase downregulated Kcna2, reduced total voltage-gated potassium current, increased excitability in DRG neurons and produced neuropathic pain symptoms. Blocking this increase reversed nerve injury-induced downregulation of DRG Kcna2 and attenuated development and maintenance of neuropathic pain. These findings suggest endogenous Kcna2 antisense RNA as a therapeutic target for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.forename: Zongxiang
authors.initials: Z
authors.lastname: Tang
authors.forename: Hongkang
authors.initials: H
authors.lastname: Zhang
authors.forename: Fidelis E
authors.initials: FE
authors.lastname: Atianjoh
authors.forename: Jian-Yuan
authors.initials: JY
authors.lastname: Zhao
authors.forename: Lingli
authors.initials: L
authors.lastname: Liang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Guan
authors.forename: Sheng-Chin
authors.initials: SC
authors.lastname: Kao
authors.forename: Vinod
authors.initials: V
authors.lastname: Tiwari
authors.forename: Yong-Jing
authors.initials: YJ
authors.lastname: Gao
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hoffman
authors.forename: Hengmi
authors.initials: H
authors.lastname: Cui
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Tao
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000235:genetics*; D020868:Gene Silencing; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D051663:Kv1.2 Potassium Channel / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D009437:Neuralgia / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D009475:Neurons, Afferent / Q000502:physiology*; D059348:Peripheral Nerve Injuries; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology
chemical_list: C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; C583791:MZF1 protein, rat; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D015534:Trans-Activators