title: Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma.
abstract: Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury-induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.
authors: Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA Department of Anatomy, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, China Department of Anesthesiology, Rutgers Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors: Zhisong
authors: Z
authors: Li
authors: Xiyao
authors: X
authors: Gu
authors: Linlin
authors: L
authors: Sun
authors: Shaogen
authors: S
authors: Wu
authors: Lingli
authors: L
authors: Liang
authors: Jing
authors: J
authors: Cao
authors: Brianna Marie
authors: BM
authors: Lutz
authors: Alex
authors: A
authors: Bekker
authors: Wei
authors: W
authors: Zhang
authors: Yuan-Xiang
authors: YX
authors: Tao
mesh_terms: D000818:Animals; D016373:DNA, Antisense / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D051663:Kv1.2 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000209:etiology* / Q000473:pathology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000150:complications*; D010812:Physical Stimulation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D016373:DNA, Antisense; D051663:Kv1.2 Potassium Channel; C583791:MZF1 protein, rat; D034741:RNA, Small Interfering; D015534:Trans-Activators
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