Selective class I histone deacetylase inhibitors suppress persistent spontaneous nociception and thermal hypersensitivity in a rat model of bee venom-induced inflammatory pain.
To confirm whether class I histone deacetylase inhibitors (HDACIs) are effective in relief of peripheral inflammatory pain, the effects of two selective inhibitors, MS-275 and MGCD0103, were studied in rats inflamed by subcutaneous (s.c.) injection of bee venom (BV). The BV test is characterized by displaying both persistent spontaneous nociception (PSN) and primary hypersensitivity. Intrathecal (i.t.) pre-treatment of either MS-275 or MGCD0103 with a single dose of 60 nmol/20 μL resulted in profound suppression of both PSN and primary thermal hypersensitivity but without significant influence upon the primary mechanical hypersensitivity and mirror-image thermal hypersensitivity. Moreover, the up-regulation of both HDAC1 and HDAC2 induced by s.c. BV injection was completely suppressed by i.t. pre-treatment of MS-275. The present results provide with another new line of evidence showing involvement of epigenetic regulation of chromatin structure by HDAC1/2-mediated histone hypoacetylation in the BV-induced PSN and thermal hypersensitivity and demonstrate the beneficial effects of class I HDACIs in prevention of peripheral inflammatory pain from occurring.
Institute for Biomedical Sciences of Pain, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Fan
F
Yang
Institute for Biomedical Sciences of Pain, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Yan
Y
Yang
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an 710038, China.
Yan
Y
Wang
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.
Fei
F
Yang
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an 710038, China.
Chun-Li
CL
Li
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an 710038, China.
Xiao-Liang
XL
Wang
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an 710038, China.
Zhen
Z
Li
Institute for Biomedical Sciences of Pain, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.|Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an 710038, China.|Beijing Institute for Brain Disorders, Beijing 100069, China. junchen@fmmu.edu.cn.
Jun
J
Chen
D000818:Animals; D001514:Bee Venoms / Q000008:administration & dosage*; D001549:Benzamides / Q000494:pharmacology; D044127:Epigenesis, Genetic; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D059225:Nociception; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy; D010147:Pain Measurement; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D001514:Bee Venoms; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C118739:entinostat; C523184:mocetinostat; C515890:Hdac1 protein, rat; C533426:Hdac2 protein, rat; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2