Park Ji-Yeun, Jang Jae-Hwan, Kang Yang-Hwa, Jeon Songhee, Kim Seung-Nam, Ryu Yeon-Hee, Park Hi-Joon
College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea.
Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea.
Integr Med Res. 2024 Sep;13(3):101051. doi: 10.1016/j.imr.2024.101051. Epub 2024 May 31.
Acupuncture has been proven effective for various types of pain, and peripheral molecular signals around acupuncture-treated areas have been suggested to contribute to the analgesic effects of acupuncture. However, the underlying mechanism from these peripheral molecular signals to central ones remains unclear. The purpose of this study was to investigate whether peripheral Rho-associated protein kinase (ROCK) activation induced by acupuncture treatment mediates acupuncture analgesia, and also to investigate the relationship between ROCK activation and extracellular signal-regulated kinase (ERK), which has previously been proven to mediate acupuncture analgesia and other related molecular changes during acupuncture.
Acupuncture was treated at the bilateral GB34 acupoints of C57BL/6 mice, after which changes in ROCK activation and the location of its expression in the skin were analyzed. To verify the role of ROCK in acupuncture analgesia, we administrated ROCK inhibitor Y-27632 (0.3 μg/ul) into the skin before acupuncture treatment with formalin and complete Freund adjuvant (CFA) induced pain models, then the nociceptive responses were analyzed.
Acupuncture treatment produced ROCK2 activation in the skin after 30 and 60 min, and the histological analyses revealed that ROCK2 was activated in the fibroblast of the dermis. The acupuncture-induced ROCK2 expression was significantly attenuated by the ERK inhibitor, whereas phospho-ERK expression was not inhibited by ROCK inhibitor. In both the formalin- and CFA-induced mouse pain models, acupuncture analgesia was blocked by ROCK inhibitor administration.
Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia.
针灸已被证明对各种类型的疼痛有效，并且有人提出针灸治疗区域周围的外周分子信号有助于针灸的镇痛作用。然而，从这些外周分子信号到中枢分子信号的潜在机制仍不清楚。本研究的目的是调查针灸治疗诱导的外周 Rho 相关蛋白激酶（ROCK）激活是否介导针灸镇痛，同时研究 ROCK 激活与细胞外信号调节激酶（ERK）之间的关系，此前已证明 ERK 在针灸镇痛及针灸过程中的其他相关分子变化中起介导作用。
对 C57BL/6 小鼠双侧足少阳胆经的阳陵泉穴进行针刺治疗，之后分析 ROCK 激活的变化及其在皮肤中的表达位置。为验证 ROCK 在针灸镇痛中的作用，在用福尔马林和完全弗氏佐剂（CFA）诱导的疼痛模型进行针刺治疗前，将 ROCK 抑制剂 Y-27632（0.3μg/μl）注入皮肤，然后分析伤害性反应。
针刺治疗 30 分钟和 60 分钟后皮肤中出现 ROCK2 激活，组织学分析显示真皮成纤维细胞中的 ROCK2 被激活。ERK 抑制剂可显著减弱针刺诱导的 ROCK2 表达，而 ROCK 抑制剂不抑制磷酸化 ERK 的表达。在福尔马林和 CFA 诱导的小鼠疼痛模型中，注射 ROCK 抑制剂均阻断了针灸镇痛。
针刺治疗诱导的 ROCK2 表达是皮肤中磷酸化 ERK 的下游效应物，在针灸镇痛中起关键作用。
