Medical Research Center of Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Road 2, Guangzhou 510080, China.
Engineering Technology Research Center for Elderly Health Management in Hainan Province, 18 Qiongshan Avenue, Haikou 571126, China.
Neuroscience. 2022 Oct 15;502:52-67. doi: 10.1016/j.neuroscience.2022.08.010. Epub 2022 Aug 17.
Mechanical allodynia impinges on the life quality of patients. Hen Egg Lysozyme (HEL) is a substance extracted from eggs that is commonly used to inhibit bacterial activity. The role of HEL in regulating and treating pain is unclear. Here, we find that HEL selectively attenuates static mechanical allodynia of mice induced by complete Freund's adjuvant (CFA), spinal nerve ligation (SNL) and chemotherapeutic agent. RNA-seq screening reveals that CFA significantly reduces the expression of Parkin in dorsal root ganglion (DRG) neurons of mice, while pre-administration of HEL increases the expression of Parkin and remits the static mechanical allodynia induced by Parkin-siRNA. Moreover, HEL increases the interaction between nuclear respiratory factor 1 (NRF1) and histone acetyltransferase P300 and then enhances the NRF1 mediated histone acetylation in prkn promoter region in DRGs of mice. Further, Parkin interacts with mechanotransducing ion channel TACAN (Tmem120a) and knockdown of Parkin significantly increases the membrane trafficking of TACAN in sensory neurons of mice. While pre-administration of HEL inhibits the increased membrane trafficking of TACAN in sensory neurons of mice induced by Parkin-siRNA. In addition, pre-given of HEL also significantly attenuates the static mechanical allodynia induced by overexpression of TACAN in mice, and the effect of HEL can be blocked by Parkin-siRNA. This indicates that HEL increases the expression of Parkin through epigenetic mechanisms and then decreases TACAN membrane trafficking in sensory neurons to relieve static mechanical hypersensitivity. Therefore, we reveal a novel function of HEL, which is a potential substance for the treatment of static mechanical pain.
机械性痛觉过敏会影响患者的生活质量。鸡卵溶菌酶（HEL）是一种从鸡蛋中提取的物质，常用于抑制细菌活性。HEL 调节和治疗疼痛的作用尚不清楚。在这里，我们发现 HEL 选择性地减轻了完全弗氏佐剂（CFA）、脊神经结扎（SNL）和化疗药物诱导的小鼠静态机械性痛觉过敏。RNA-seq 筛选表明，CFA 显著降低了小鼠背根神经节（DRG）神经元中 Parkin 的表达，而 HEL 的预先给药增加了 Parkin 的表达，并缓解了 Parkin-siRNA 诱导的静态机械性痛觉过敏。此外，HEL 增加了核呼吸因子 1（NRF1）和组蛋白乙酰转移酶 P300 之间的相互作用，然后增强了 DRG 中 prkn 启动子区域中 NRF1 介导的组蛋白乙酰化。此外，Parkin 与机械转导离子通道 TACAN（Tmem120a）相互作用，Parkin 的敲低显著增加了小鼠感觉神经元中 TACAN 的膜转运。而 HEL 的预先给药抑制了 Parkin-siRNA 诱导的小鼠感觉神经元中 TACAN 膜转运的增加。此外，HEL 预先给药还显著减轻了 TACAN 在小鼠中过表达诱导的静态机械性痛觉过敏，而 HEL 的作用可以被 Parkin-siRNA 阻断。这表明 HEL 通过表观遗传机制增加 Parkin 的表达，然后减少感觉神经元中 TACAN 的膜转运，从而缓解静态机械性超敏。因此，我们揭示了 HEL 的一个新功能，它是治疗静态机械性疼痛的潜在物质。
