title: Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model.
abstract: The management of neuropathic pain is still a major challenge because of its unresponsiveness to most common treatments. Curcumin has been reported to play an active role in the treatment of various neurological disorders, such as neuropathic pain. Curcumin has long been recognized as a p300/CREB-binding protein (CBP) inhibitor of histone acetyltransferase (HAT) activity. However, this mechanism has never been investigated for the treatment of neuropathic pain with curcumin. The aim of the present study was to investigate the anti-nociceptive role of curcumin in the chronic constriction injury (CCI) rat model of neuropathic pain. Furthermore, with this model we investigated the effect of curcumin on P300/CBP HAT activity-regulated release of the pro-nociceptive molecules, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (Cox-2). Treatment with 40 and 60 mg/kg body weight curcumin for 7 consecutive days significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, whereas 20 mg/kg curcumin showed no significant analgesic effect. Chromatin immunoprecipitation analysis revealed that curcumin dose-dependently reduced the recruitment of p300/CBP and acetyl-Histone H3/acetyl-Histone H4 to the promoter of BDNF and Cox-2 genes. A similar dose-dependent decrease of BDNF and Cox-2 in the spinal cord was also observed after curcumin treatment. These results indicated that curcumin exerted a therapeutic role in neuropathic pain by down-regulating p300/CBP HAT activity-mediated gene expression of BDNF and Cox-2.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Liver Cancer Laboratory, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Zongbing
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Huang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D006657:Histones; D051546:Cyclooxygenase 2; D050880:p300-CBP Transcription Factors; D003474:Curcumin; D008239:Lysine