title: Contribution of the Suppressor of Variegation 3-9 Homolog 1 in Dorsal Root Ganglia and Spinal Cord Dorsal Horn to Nerve Injury-induced Nociceptive Hypersensitivity.
abstract: Peripheral nerve injury-induced gene alterations in the dorsal root ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis. Histone methylation gates gene expression. Whether the suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury-induced nociceptive hypersensitivity is unknown.
  
  
  
  Quantitative real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, or immunohistochemistry were carried out to examine the expression of SUV39H1 mRNA and protein in rat DRG and dorsal horn and its colocalization with DRG μ-opioid receptor (MOR). The effects of a SUV39H1 inhibitor (chaetocin) or SUV39H1 siRNA on fifth lumbar spinal nerve ligation (SNL)-induced DRG MOR down-regulation and nociceptive hypersensitivity were examined.
  
  
  
  SUV39H1 was detected in neuronal nuclei of the DRG and dorsal horn. It was distributed predominantly in small DRG neurons, in which it coexpressed with MOR. The level of SUV39H1 protein in both injured DRG and ipsilateral fifth lumbar dorsal horn was time dependently increased after SNL. SNL also produced an increase in the amount of SUV39H1 mRNA in the injured DRG (n = 6/time point). Intrathecal chaetocin or SUV39H1 siRNA as well as DRG or intraspinal microinjection of SUV39H1 siRNA impaired SNL-induced allodynia and hyperalgesia (n = 5/group/treatment). DRG microinjection of SUV39H1 siRNA also restored SNL-induced DRG MOR down-regulation (n = 6/group).
  
  
  
  The findings of this study suggest that SUV39H1 contributes to nerve injury-induced allodynia and hyperalgesia through gating MOR expression in the injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of nerve injury-induced nociceptive hypersensitivity.
authors.affiliation: From the Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey (J.Z., L.L., X.M., S.W., J.C., Q.M., K.M., M.X., B.M.L., A.B., Y.-X.T.); Department of Anesthesiology, Union Medical Center, Nankai University, Tianjin, China (J.Z.); Department of Anesthesiology and Intensive Care, Eastern Hepatobiliary Surgical Hospital, The Second Military Medical University, Shanghai, China (X.M.); Rowan University School of Osteopathic Medicine, Stratford, New Jersey (B.T.); Department of Anesthesiology, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China (Q.M.); and Departments of Cell Biology and Molecular Medicine (Y.-X.T.) and Physiology, Pharmacology and Neuroscience (Y.-X.T.), New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Lingli
authors.initials: L
authors.lastname: Liang
authors.forename: Xuerong
authors.initials: X
authors.lastname: Miao
authors.forename: Shaogen
authors.initials: S
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.forename: Bo
authors.initials: B
authors.lastname: Tao
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Mao
authors.forename: Kai
authors.initials: K
authors.lastname: Mo
authors.forename: Ming
authors.initials: M
authors.lastname: Xiong
authors.forename: Brianna Marie
authors.initials: BM
authors.lastname: Lutz
authors.forename: Alex
authors.initials: A
authors.lastname: Bekker
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Tao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; C512117:Suv39h1 protein, rat; D008780:Methyltransferases