title: p300 exerts an epigenetic role in chronic neuropathic pain through its acetyltransferase activity in rats following chronic constriction injury (CCI).
abstract: BACKGROUND
  Neuropathic pain is detrimental to human health; however, its pathogenesis still remains largely unknown. Overexpression of pain-associated genes and increased nociceptive somato-sensitivity are well observed in neuropathic pain. The importance of epigenetic mechanisms in regulating the expression of pro- or anti-nociceptive genes has been revealed by studies recently, and we hypothesize that the transcriptional coactivator and the histone acetyltransferase E1A binding protein p300 (p300), as a part of the epigenetic mechanisms of gene regulation, may be involved in the pathogenesis of neuropathic pain induced by chronic constriction injury (CCI). To test this hypothesis, two different approaches were used in this study: (I) down-regulating p300 with specific small hairpin RNA (shRNA) and (II) chemical inhibition of p300 acetyltransferase activity by a small molecule inhibitor, C646.
  
  
  RESULTS
  Using the CCI rat model, we found that the p300 expression was increased in the lumbar spinal cord on day 14 after CCI. The treatment with intrathecal p300 shRNA reversed CCI-induced mechanical allodynia and thermal hyperalgesia, and suppressed the expression of cyclooxygenase-2 (COX-2), a neuropathic pain-associated factor. Furthermore, C646, an inhibitor of p300 acetyltransferase, also attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord.
  
  
  CONCLUSIONS
  The results suggest that, through its acetyltransferase activity in the spinal cord after CCI, p300 epigenetically plays an important role in neuropathic pain. Inhibiting p300, using interfering RNA or C646, may be a promising approach to the development of new neuropathic pain therapies.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha City, Hunan, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhu
authors.forename: Chang-Sheng
authors.initials: CS
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Chang
authors.forename: Zong-Bing
authors.initials: ZB
authors.lastname: Song
authors.forename: Wang-Yuan
authors.initials: WY
authors.lastname: Zou
authors.forename: Qu-Lian
authors.initials: QL
authors.lastname: Guo
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D059350:Chronic Pain / Q000235:genetics / Q000378:metabolism*; D003251:Constriction, Pathologic; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D057890:Epigenomics; D008297:Male; D009437:Neuralgia / Q000201:enzymology* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D051546:Cyclooxygenase 2; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor