title: RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.
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 toAdar2+/+/Gria2R/Rlittermate controls,Adar2-/-/Gria2R/Rmice 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.
authors.affiliation: Department of Medical Chemistry, Kansai Medical University, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Department of Medical Chemistry, Kansai Medical University, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsumura
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Tokyo, Japan; and.
authors.forename: Shunpei
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Tokyo, Japan; and.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Anesthesiology, Osaka Medical College, Osaka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Minami
authors.affiliation: Department of Medical Chemistry, Kansai Medical University, Osaka, Japan; ito@hirakata.kmu.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D009437:Neuralgia / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000235:genetics* / Q000378:metabolism; D017393:RNA Editing; D016601:RNA-Binding Proteins / Q000235:genetics*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D012701:Serotonin; C000595151:ADAR2 protein, mouse; D000243:Adenosine Deaminase; C051409:pegademase bovine
keywords: adenosine deaminase; dorsal root ganglion; posttranscriptional regulation; tactile allodynia