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FASEB J. 2017 May;31(5):1847-1855. doi: 10.1096/fj.201600950R. Epub 2017 Jan 26.

RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.

Author information

1
Department of Medical Chemistry, Kansai Medical University, Osaka, Japan.
2
Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Tokyo, Japan; and.
3
Department of Anesthesiology, Osaka Medical College, Osaka, Japan.
4
Department of Medical Chemistry, Kansai Medical University, Osaka, Japan; ito@hirakata.kmu.ac.jp.

Abstract

Transcriptional and post-translational regulations are important in peripheral nerve injury-induced neuropathic pain, but little is known about the role of post-transcriptional modification. Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze post-transcriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs). These changes were accompanied by elevated levels of editing at the D site of the serotonin (5-hydroxytryptamine) 2C receptor (5-HT2CR), at the I/V site of coatomer protein complex subunit α (COPA), and at the R/G site of AMPA receptor subunit GluA2 in the injured DRG. Compared to Adar2+/+/Gria2R/R littermate controls, Adar2-/-/Gria2R/R mice completely lacked the increased editing of 5-HT2CR, COPA, and GluA2 transcripts in the injured DRG and showed attenuated tactile allodynia after SNT. Furthermore, the antidepressant fluoxetine inhibited neuropathic allodynia after injury and reduced the COPA I/V site editing in the injured DRG. These findings suggest that ADAR2 is a mediator of injury-induced tactile allodynia and thus a potential therapeutic target for the treatment of neuropathic pain.-Uchida, H., Matsumura, S., Okada, S., Suzuki, T., Minami, T., Ito, S. RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.

KEYWORDS:

adenosine deaminase; dorsal root ganglion; posttranscriptional regulation; tactile allodynia

PMID:
28126736
DOI:
10.1096/fj.201600950R
[Indexed for MEDLINE]

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