The Effect of Anaesthetic-Induced Activation and Sensitization of Transient Receptor Potential Ion Channels on the Development of Chronic Pain Syndromes

慢性疼痛综合征，特别是神经性疼痛，可作为外科手术的后果（例如在治疗乳腺癌期间）发生，是一个严重的治疗问题。临床研究报告表明，麻醉的选择可以影响急性术后疼痛和慢性疼痛综合征的发生。不仅麻醉技术（区域麻醉与全身麻醉），而且麻醉物质的选择似乎也起着重要作用。近年来，急性术后疼痛的发生与麻醉诱导的瞬时受体电位（TRP）通道家族的调节有关。该离子通道家族的几个亚型在伤害性神经元中表达，在那里它们作为热和化学刺激的传感器发挥作用。许多临床应用的麻醉药已知可激活和致敏通道亚型TRPA和TRPV。鉴于trp通道激活和致敏对急性和慢性疼痛综合征发展的潜在影响，麻醉似乎很可能也会影响手术治疗后慢性疼痛综合征的发作。因此，本研究旨在阐明麻醉剂与这一受体通道家族相互作用的机制，并进一步阐明它们对疼痛发展的影响。因此，该项目的第一部分涉及表征和比较TRPA和TRPV通道的激活和体外不同全身麻醉剂的致敏。在本项目的第二部分，我们将在一个已建立的动物模型中评估麻醉诱导的TRPA和TRPV通道激活和致敏对慢性疼痛综合征发展的影响。了解这些机制可能有助于我们更合理地利用麻醉剂，试图预防或至少大大减少慢性疼痛综合征的发展。

Chronic pain syndromes, especially neuropathic pain, can occur as a consequence of surgical procedures (e.g. during treatment of breast cancer) and represent a severe therapeutical problem. Reports from clinical research have indicated that the choice of anaesthesia can influence the occurrence of acute postoperative pain and chronic pain syndromes. Not only the technique of anaesthesia (regional versus general anaesthesia), but also the choice of anaesthetic substances seems to play an important role. Recently, the development of acute postoperative pain was related to the anaesthetic-induced modulation of the transient receptor potential (TRP) channel family. Several subtypes of this ion channel family are expressed in nociceptive neurons, where they function as sensors of thermal and chemical stimuli. Many of the clinically applied anaesthetics are known to activate and sensitize the channel subtypes TRPA and TRPV. Given the potential impact of TRP-channel activation and sensitization on the development of acute and chronic pain syndromes it seems very likely that anaesthetics can also influence the onset of chronic pain syndromes after surgical treatments. Therefore, this study aims at elucidating the mechanisms by which anaesthetics interact with this family of receptor channels and to further elucidate their effects on pain development. Hence, the first part of the project involves the characterisation and comparison of TRPA and TRPV channel activation and sensitisation by different general anaesthetics in vitro. In the second part of this project, the effects of anaesthetic-induced TRPA and TRPV channel activation and sensitisation on the development of chronic pain syndromes will be assessed in vivo in an established animal model. Understanding these mechanisms may help us to exploit anaesthetics more rationally in trying to prevent or at least considerably reduce the development of chronic pain syndromes.