Thermo-sensitive TRP channels in peripheral nerve injury: A review of their role in cold intolerance

Summary One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background of thermal intolerance, we focus first on the various transient receptor potential (TRP) channels that are involved in temperature sensation, including their presence in peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP channels in cold and heat intolerance is described showing three different mechanisms that contribute to thermal intolerance in the skin: (a) an increased expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower activation threshold of TRP channels and (c) the sprouting of non-injured nerve fibres. Finally, the data that are available on the effects of TRP channel agonists and antagonists and their clinical use are discussed. In conclusion, TRP channels play a major role in temperature sensation and in cold and heat intolerance. Unfortunately, the available pharmaceutical agents that successfully target TRP channels and counteract thermal intolerance are still very limited. Yet, our focus should remain on TRP channels since it is difficult to imagine a reliable treatment for thermal intolerance that will not involve TRP channels.