title: Mechanisms of cold pain.
abstract: Avoidance of cold pain is an important survival mechanism. Intriguingly, whilst cooling can cause numbness, damage sensing mechanisms still seem to operate at low temperatures, and pain can be perceived from cooled damaged tissue. Recent studies have identified two cold-activated transient receptor potential (TRP) channels present in sensory neurons as transducers of cold stimuli. TRPM8 seems to mediate responses to cooling whilst TRPA1 is activated, possibly indirectly, by more extreme cold conditions. The existence of cold-responsive neurons that do not express these channels suggests that other transducers of cold stimuli remain to be discovered. Subsequent action potential electrogenesis and probably propagation from sensory neurons innervating cold tissues depends upon the presence of Na(v)1.8, the sole voltage-gated sodium channel that fails to inactivate at low temperatures. This may explain the remarkable specificity of Na(v)1.8 expression in nociceptive neurons, where it plays an important role in pain pathways.
authors.affiliation: Molecular Nociception Group, University College London, London, UK. t.foulkes@ucl.ac.uk
authors.forename: Thomas
authors.initials: T
authors.lastname: Foulkes
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
mesh_terms: D000200:Action Potentials; D000698:Analgesia / Q000379:methods; D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism; D007036:Hypothermia, Induced; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009434:Neural Pathways / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D059408:Pain Management; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission; D050053:TRPM Cation Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D007473:Ion Channels; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human; D015222:Sodium Channels; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels