Purpose: Persistent inflammatory or neuropathic pain is common in clinical practice. DNA methylation is reported to be involved in chronic pain, but its function has not been fully investigated. Thus, our study aimed to investigate the role of Dnmt3a in the superficial dorsal horn in regulating the maintenance phase of persistent pain at cellular and behavioral levels.
Methods: CFA-induced chronic pain adult male SD rat model was established by injecting CFA into the left talocrural joint. Thermal Withdrawal Latency (TWL) and Mechanical Withdrawal Threshold (PWT) were used for determining the pain degree. Real-time RT-PCR and western blot were used to detect the DNA and protein expression. The specimen of lumbar 4-6 spinal cords was collected.
Results: DNA methylation and DNA methyltransferase Dnmt3a activity in the superficial dorsal horn was associated with chronic inflammatory pain in CFA rat model and Dnmt3a expression was upregulated. Intrathecal Dnmt3a-Pr aggravated hyperalgesia, while intrathecal Dnmt3a-siRNA reversed the chronic inflammatory persistent pain. Our in vivo data indicated that Dnmt3a-siRNA could alleviate inflammatory pain.
Conclusion: Dnmt3a could participate in the mediation of chronic persistent pain at cellular and behavioral levels, which may be identified as a new therapeutic agent for treating such disease.