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，可作为外科手术的结果（例如在乳腺癌的治疗期间）发生，并且代表严重的治疗问题。来自临床研究的报告表明，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（局部麻醉与全身麻醉），而且麻醉物质的选择似乎也起着重要作用。最近，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种亚型在伤害感受神经元中表达，在那里它们充当热和化学刺激的传感器。已知许多临床应用的麻醉剂激活和敏化通道亚型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，麻醉剂似乎也很可能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该受体通道家族相互作用的机制，并进一步阐明其对疼痛发展的影响。因此，该项目的第一部分涉及TRPA和TRPV通道激活和不同的全身麻醉剂在体外致敏的表征和比较。在该项目的第二部分，麻醉诱导的TRPA和TRPV通道激活和致敏对慢性疼痛综合征的发展的影响将在建立的动物模型中进行体内评估。了解这些机制可能有助于我们更合理地利用麻醉剂来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.