Suppression of HDAC2 in Spinal Cord Alleviates Mechanical Hyperalgesia and Restores KCC2 Expression in a Rat Model of Bone Cancer Pain

Neuroscience
Xinran HouQulian Guo

Abstract

Epigenetic modulation participates in the mechanism of multiple types of pathological pain, so targeting the involved regulators may be a promising strategy for pain treatment. Our previous research identified the analgesic effect of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) on mechanical hyperalgesia in a rat model of bone cancer pain (BCP) via restoration of μ-opioid receptor (MOR) expression. However, the specific types of HDACs contributing to BCP have not been explored. The present study investigated the expression pattern of some common HDACs and found that HDAC2 was up-regulated in a time-dependent manner in the lumbar spinal cord of BCP rats. TSA application suppressed HDAC2 expression in cultured PC12 cells and reversed the augmented HDAC2 in BCP rats. An RNA-interfering strategy confirmed the essential role of HDAC2 in the modulation of mechanical hyperalgesia following tumor cell inoculation, and we further examined its possible downstream targets. Notably, HDAC2 knock-down did not restore MOR expression, but it robustly reversed the down-regulation of potassium-chloride cotransporter 2 (KCC2). The impaired KCC2 expression is a vital mechanism of many types of pathological pain. Therefore, our res...Continue Reading

Citations

Jul 5, 2019·Cellular and Molecular Neurobiology·Chengwei YangJuan Li
Apr 23, 2021·The Clinical Journal of Pain·Xin YangChangsheng Huang
Jun 4, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Manasa Gangadhar ShettyKampa Sundara Babitha

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