title: Epigenetic modulation of Wnt signaling contributes to neuropathic pain in rats.
abstract: Previous studies have demonstrated that the Wnt/β‑catenin signaling pathway is critical to the induction and maintenance of chronic neuropathic pain caused by peripheral inflammation and nerve damage. Emerging evidence from recent studies suggests that epigenetic mechanisms may also be critical to the pathogenesis of chronic pain. The present study aimed to elucidate the epigenetic mechanisms underlying altered Wnt signaling and their involvement in CCI‑induced neuropathic pain in rat sciatic nerves. The results of the present study demonstrated a significant increase in the expression levels of Wnt3a in the dorsal horn of the rats with CCI. In addition, a significant increase in histone H3 acetylation, and a significant decrease in cytosine methylation in the promoter region of Wnt3a was observed in the dorsal horn of the rats with CCI. Intrathecal application of XAV939, which acts as an inhibitor of Wnt signaling, significantly decreased the expression levels of active β‑catenin, and attenuated the rat behavioral responses to thermal and mechanical pain stimuli. These results suggest that the epigenetic upregulation of Wnt3a in the dorsal horn contributes to the maintenance of pain‑induced behavior in rats with CCI.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors.forename: Ruynag
authors.initials: R
authors.lastname: Teng
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors.forename: Haichen
authors.initials: H
authors.lastname: Chu
mesh_terms: D000107:Acetylation; D000818:Animals; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017208:Rats, Wistar; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D060509:Wnt3A Protein