Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) after peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal responses to acute mechanical, heat, and cold stimuli as well as locomotor functions. Mimicking this increase through microinjection of recombinant adeno-associated virus 5 harboring full-length OCT1 into the unilateral L4/5 DRG led to marked mechanical allodynia, heat hyperalgesia, and cold allodynia in naive rats. Mechanistically, OCT1 participated in CCI-induced increases in Dnmt3a mRNA and its protein and DNMT3a-mediated decreases in Oprm1 and Kcna2 mRNAs and their proteins in the injured DRG. These findings indicate that OCT1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG. OCT1 may serve as a potential target for therapeutic treatments against neuropathic pain.
Dorsal root ganglion octamer transcription factor 1 participates in neuropathic pain by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the dorsal root ganglion.
aDepartment of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
bDepartment of Anesthesiology, New Jersey Medical School, Rutgers the State University of New Jersey, Newark, NJ, United States
cNeuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
Corresponding author. Address: Department of Anesthesiology, New Jersey Medical School, Rutgers the State University of New Jersey, 185 S. Orange Ave, MSB, E-661, Newark, NJ 07103, United States. Tel.: +1-973-972-9812; fax: +1-973-972-1644. E-mail address: email@example.com (Y.-X. Tao).
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J. Yuan and J. Wen contributed equally to this work.
Received April 15, 2018
Received in revised form July 28, 2018
Accepted August 16, 2018