Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury

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.
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Original Research Articles: CME Article . 2019 Series . Number 11 Source Type: research
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Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Original Research Articles Source Type: research
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Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Original Research Articles Source Type: research
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Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Original Research Articles Source Type: research
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Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Education & Administration Source Type: research
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Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Brief Report Source Type: research
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Source: NeuroImage: Clinical - Category: Radiology Source Type: research
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Source: Journal of Clinical Orthopaedics and Trauma - Category: Orthopaedics Source Type: research
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Source: The Back Letter - Category: Orthopaedics Tags: Articles Source Type: research
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