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

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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.