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Selective class I histone deacetylase inhibitors suppress persistent spontaneous nociception and thermal hypersensitivity in a rat model of bee venom-induced inflammatory pain

Yang Fan, YANG Yan, WANG Yan, YANG Fei, LI Chun-Li, WANG Xiao-Liang, LI Zhen, CHEN Jun

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

Abstract

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.

Key words: bee venom; histone deacetylase; persistent spontaneous nociception; thermal hypersensitivity; mechanical hypersensitivity

Received: 2015-04-24　　Accepted: 2015-05-20

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Citing This Article：

Yang Fan, YANG Yan, WANG Yan, YANG Fei, LI Chun-Li, WANG Xiao-Liang, LI Zhen, CHEN Jun. Selective class I histone deacetylase inhibitors suppress persistent spontaneous nociception and thermal hypersensitivity in a rat model of bee venom-induced inflammatory pain. Acta Physiol Sin 2015; 67 (5): 447-454 (in Chinese with English abstract).