Ji-Yeun Park , Jae-Hwan Jang , Yang-Hwa Kang , Songhee Jeon , Seung-Nam Kim , Yeon-Hee Ryu , Hi-Joon Park
{"title":"外周Rho相关蛋白激酶激活介导针灸镇痛","authors":"Ji-Yeun Park , Jae-Hwan Jang , Yang-Hwa Kang , Songhee Jeon , Seung-Nam Kim , Yeon-Hee Ryu , Hi-Joon Park","doi":"10.1016/j.imr.2024.101051","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia.</p></div>","PeriodicalId":13644,"journal":{"name":"Integrative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213422024000313/pdfft?md5=076c13229f5183f86580521085313c36&pid=1-s2.0-S2213422024000313-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Peripheral Rho-associated protein kinase activation mediates acupuncture analgesia\",\"authors\":\"Ji-Yeun Park , Jae-Hwan Jang , Yang-Hwa Kang , Songhee Jeon , Seung-Nam Kim , Yeon-Hee Ryu , Hi-Joon Park\",\"doi\":\"10.1016/j.imr.2024.101051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia.</p></div>\",\"PeriodicalId\":13644,\"journal\":{\"name\":\"Integrative Medicine Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-05-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2213422024000313/pdfft?md5=076c13229f5183f86580521085313c36&pid=1-s2.0-S2213422024000313-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Integrative Medicine Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213422024000313\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Integrative Medicine Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213422024000313","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
针灸已被证明对各种疼痛有效,针灸治疗区域周围的外周分子信号被认为有助于针灸的镇痛效果。然而,从这些外周分子信号到中枢信号的内在机制仍不清楚。本研究的目的是探讨针刺治疗诱导的外周Rho相关蛋白激酶(ROCK)活化是否介导针刺镇痛,同时探讨ROCK活化与细胞外信号调节激酶(ERK)之间的关系。对 C57BL/6 小鼠的双侧 GB34 穴位进行针刺治疗后,分析了 ROCK 活化的变化及其在皮肤中的表达位置。为了验证ROCK在针刺镇痛中的作用,我们在针刺治疗前给皮肤注射ROCK抑制剂Y-27632(0.3 μg/ul),并用福尔马林和完全弗氏佐剂(CFA)诱导疼痛模型,然后分析痛觉反应。针刺治疗30分钟和60分钟后,皮肤中的ROCK2被激活,组织学分析表明真皮层成纤维细胞中的ROCK2被激活。针刺诱导的 ROCK2 表达在 ERK 抑制剂的作用下明显减弱,而 ROCK 抑制剂并未抑制磷酸化 ERK 的表达。在福尔马林和CFA诱导的小鼠疼痛模型中,针刺镇痛均被ROCK抑制剂阻断。针刺治疗诱导的ROCK2表达是皮肤中磷酸-ERK的下游效应因子,在针刺镇痛中起着至关重要的作用。
Peripheral Rho-associated protein kinase activation mediates acupuncture analgesia
Background
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.
Methods
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.
Results
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.
Conclusion
Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia.
期刊介绍:
Integrative Medicine Research (IMR) is a quarterly, peer-reviewed journal focused on scientific research for integrative medicine including traditional medicine (emphasis on acupuncture and herbal medicine), complementary and alternative medicine, and systems medicine. The journal includes papers on basic research, clinical research, methodology, theory, computational analysis and modelling, topical reviews, medical history, education and policy based on physiology, pathology, diagnosis and the systems approach in the field of integrative medicine.