Role of purinergic signaling in acupunctureinduced analgesia

这三位申请人（以及德国共同申请人PD Heike Franke）自2012年10月10日至15日在成都举行的第一届中德针灸、嘌呤能信号和疼痛研讨会以来一直在合作。根据我们对嘌呤能信号参与疼痛和针刺镇痛的认识以及他们支持这一假说的初步工作，唐勇教授（中国成都中医药大学）、荣卫芳教授（中国上海交通大学）和Peter Illes教授（德国莱比锡大学）提出了一个新的假说来解释针刺镇痛的机制。因此，不同的嘌呤受体及其相互作用的皮肤穴位，背根神经节（DRG）和头端腹内侧延髓（RVM）可能有助于针刺镇痛。为了加强这一新的假设，来自不同学科和互补实验经验的三个研究小组的所有科学家将专注于炎症和神经病理性疼痛，并采用各种方法，如痛阈测试，微透析，高效液相色谱（HPLC），体内和体外电生理记录，分子生物学方法，免疫荧光，实时定量PCR，Western blot，基因敲除和嘌呤受体激动剂和拮抗剂在功能研究中的应用，以推进对这一实验和临床重要问题的研究。特别重要的是，他们的研究将在外周和中枢神经系统的不同层次上进行（见上文）。我们相信，这种综合的方法和三个小组的联合力量和能力将教会我们如何利用针灸嘌呤能机制来减轻疼痛。整个项目的概述，强调每个研究小组的作用和动机，他们的预期互动和预期的附加值。这个拟议的项目将主要集中在皮肤穴位的嘌呤受体及其相互作用，背根神经节（DRG）和延髓头端腹外侧区（RVM）的变化，以揭示针刺对炎性痛和神经病理性痛的镇痛机制。为了完成这个项目，我们将成立三个研究团队，一个由Peter Illes教授和他的共同申请人PD Heike Franke领导的莱比锡大学（莱比锡团队），一个由Weifang Rong教授领导的上海交通大学（上海团队）和另一个由Yong Tang教授领导的成都中医药大学（成都团队）。成都团队将专注于皮肤穴位嘌呤受体介导的效应，而莱比锡团队将专注于位于DRG的嘌呤受体的分子生物学和功能特征，上海团队将专注于位于RVM的嘌呤受体。除了进行独立的研究外，每个团队将保持密切沟通，相互交流思想，并在针灸，嘌呤能信号或疼痛的研究领域为其他两个团队提供独特的支持。预计一些博士生将在参与实验室接受培训，我们的数据将发表在高影响力的科学期刊上。第二届中德针灸、嘌呤能信号与疼痛研讨会将于2016年秋季在莱比锡举行。此外，我们计划成立中德针灸镇痛研究小组，研究针灸镇痛的机制。

The three applicants (and the German co-applicant PD Heike Franke) have been working together since The First Chinese-German Symposium on Acupuncture, Purinergic signaling & Pain, funded by The Sino-German Center for Research Promotion, took place in Chengdu from October 10 to 15, 2012. Professor Yong Tang (Chengdu University of Traditional Chinese Medicine, China), Professor Weifang Rong (Shanghai Jiaotong University, China) and Professor Peter Illes (University of Leipzig, Germany) propose now a new hypothesis to explain the mechanism of acupuncture analgesia based on the current increase of our knowledge on the participation of purinergic signaling in pain and acupuncture analgesia and their preliminary work supporting this hypothesis. Thus, different purine receptors and their interaction at the cutaneous acupoints, at dorsal root ganglia (DRG) and the rostral ventromedial medulla (RVM) might contribute to acupuncture-induced analgesia. To strengthen this novel hypothesis, all scientists of the three research teams from different disciplines and complementary experimental experience will focus on inflammatory and neuropathic pain and employ various approaches, such as pain threshold test, microdialysis, high performance liquid chromatography (HPLC), in vivo and in vitro electrophysiological recordings, molecular biology methods, immunofluorescence, real-time quantitative PCR, Western blot, gene knockout and the use of purine receptor agonists and antagonists in functional studies to forward research on this experimentally and clinically important issue. It is of particular significance, that their research will be executed at different hierarchical levels of the peripheral and central nervous system (see above). We are confident that this integrative approach and the combined forces and competence of the three groups will teach us how acupuncture utilizes purinergic mechanisms to alleviate pain.General description of the overall project, emphasizing the role and motivation of eachResearch Team, their intended interaction and the anticipated added value.This proposed project will mainly focus on the purine receptors and their interactions at cutaneous acupuncture points, the dorsal root ganglia (DRG) and the rostral ventrolateral medulla (RVM) to reveal the mechanism of acupuncture analgesia in inflammatory and neuropathic pain. To complete this proposed project, we will establish three research teams, one from University of Leipzig led by Professor Peter Illes and his co-applicant PD Heike Franke (Leipzig team), one from Shanghai Jiaotong University led by Professor Weifang Rong (Shanghai team) and another from Chengdu University of Traditional Chinese Medicine led by Professor Yong Tang (Chengdu team). Chengdu team will concentrate on purine receptor-mediated effects at a cutaneous acupuncture point, while Leipzig team will focus on the molecular biological and functional characteristics of purine receptors located at DRGs and Shanghai team on those located at RVM. Apart from performing independent research, each team will keep close communication, exchange ideas with each other and provide its unique support in the research field of acupuncture, purinergic signaling or pain to the other two teams. It is anticipated that a number of PhD students will be trained in the participating laboratories, and our data will be published in high impact scientific journals. The 2nd Sino-German Symposium on Acupuncture, Purinergic signaling & Pain will be organized in Leipzig in the autumn of 2016. Additionally, we plan to set up a Sino-German Acupuncture Analgesia Group for studying the mechanism of acupuncture-induced analgesia.