Feng Wei, Teng Ruynag, Zhao Yang, Gao Jie, Chu Haichen
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
Mol Med Rep. 2015 Sep;12(3):4727-4733. doi: 10.3892/mmr.2015.3972. Epub 2015 Jun 22.
Previous studies have demonstrated that the Wnt/β‑catenin signaling pathway is critical to the induction and maintenance of chronic neuropathic pain caused by peripheral inflammation and nerve damage. Emerging evidence from recent studies suggests that epigenetic mechanisms may also be critical to the pathogenesis of chronic pain. The present study aimed to elucidate the epigenetic mechanisms underlying altered Wnt signaling and their involvement in CCI‑induced neuropathic pain in rat sciatic nerves. The results of the present study demonstrated a significant increase in the expression levels of Wnt3a in the dorsal horn of the rats with CCI. In addition, a significant increase in histone H3 acetylation, and a significant decrease in cytosine methylation in the promoter region of Wnt3a was observed in the dorsal horn of the rats with CCI. Intrathecal application of XAV939, which acts as an inhibitor of Wnt signaling, significantly decreased the expression levels of active β‑catenin, and attenuated the rat behavioral responses to thermal and mechanical pain stimuli. These results suggest that the epigenetic upregulation of Wnt3a in the dorsal horn contributes to the maintenance of pain‑induced behavior in rats with CCI.
先前的研究表明，Wnt/β-连环蛋白信号通路对于由外周炎症和神经损伤引起的慢性神经性疼痛的诱导和维持至关重要。近期研究的新证据表明，表观遗传机制可能对慢性疼痛的发病机制也至关重要。本研究旨在阐明Wnt信号改变背后的表观遗传机制及其在大鼠坐骨神经慢性压迫损伤（CCI）诱导的神经性疼痛中的作用。本研究结果表明，CCI大鼠背角中Wnt3a的表达水平显著增加。此外，在CCI大鼠的背角中观察到组蛋白H3乙酰化显著增加，且Wnt3a启动子区域的胞嘧啶甲基化显著降低。鞘内注射作为Wnt信号抑制剂的XAV939，显著降低了活性β-连环蛋白的表达水平，并减弱了大鼠对热和机械性疼痛刺激的行为反应。这些结果表明，背角中Wnt3a的表观遗传上调有助于维持CCI大鼠的疼痛诱导行为。
