Pain Medicine  |   October 2016
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
Author Notes
  • 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.
  • Submitted for publication December 27, 2015. Accepted for publication June 6, 2016.
    Submitted for publication December 27, 2015. Accepted for publication June 6, 2016.×
  • Corresponding article on page 627. J.Z., L.L., and X.M. equally contributed to this work.
    Corresponding article on page 627. J.Z., L.L., and X.M. equally contributed to this work.×
  • Address correspondence to Dr. Tao: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 S. Orange Ave., MSB, F-548, Newark, New Jersey 07103. yuanxiang.tao@njms.rutgers.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Basic Science / Central and Peripheral Nervous Systems / Pain Medicine
Pain Medicine   |   October 2016
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
Anesthesiology 10 2016, Vol.125, 765-778. doi:10.1097/ALN.0000000000001261
Anesthesiology 10 2016, Vol.125, 765-778. doi:10.1097/ALN.0000000000001261
Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.