Burning Cold: Involvement of TRPA1 in Noxious Cold Sensation

Soon after its discovery ten years ago, the ion channel TRPA1 was proposed as a sensor of noxious cold. Evidence for its activation by painfully cold temperatures (below similar to 15 degrees C) has been mixed, however. Some groups found that cold elicits a nonselective conductance in cells expressing TRPA1; others found no activation, or argued that activation is an indirect effect of elevated Ca2+. Sensory cells from the trigeminal and dorsal root ganglia that are activated by cold were sometimes correlated with those cells expressing TRPA1; other times not. Mice lacking TRPA1 showed behavioral deficits for some assays of painful cold sensation, but not others. New evidence tends to support direct activation of TRPA1 by cold, and the slow and relatively weak activation of TRPA1 by cold helps reconcile some conflicting studies.