Explorer Cold comfort pharm

General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Abstract 15 Cooling of the skin has long been thought to be beneficial in pain states but 16 intense cold is clearly noxious. Does cooling lead to pain or gain? Rapid progress 17 in this controversy has been made since the discovery of specific ion channels of 18 the TRP family that are activated by cooling of sensory nerve cells to below body 19 temperature. This review focuses on the role of one of these, TRPM8, which has 20 been implicated in cool sensation and cold pain by recent knockout mouse 21 studies, but remarkably also appears capable of eliciting a novel analgesic gating 22 control over noxious inputs in chronic pain states. We discuss hypothetical 23 mechanisms that could bring about this composite profile. It is clear that new and 24 highly selective agents will need to be developed to further evaluate the potential 25 therapeutic opportunities offered by low temperature-sensitive TRP channels.