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RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury
Author(s) -
Uchida Hitoshi,
Matsumura Shinji,
Okada Shunpei,
Suzuki Tsutomu,
Minami Toshiaki,
Ito Seiji
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600950r
Subject(s) - neuropathic pain , mediator , peripheral nerve injury , peripheral , medicine , nerve injury , peripheral nerve , enzyme , neuroscience , chemistry , anesthesia , anatomy , biology , biochemistry
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 posttranscriptional 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‐HT 2C R), 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 +/+ /Gria2 R/R littermate controls, Adar2 ‒ / ‒ /Gria2 R/R mice completely lacked the increased editing of 5‐HT 2C R, 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. FASEB J. 31, 1847–1855 (2017). www.fasebj.org