343 the Contribution of Trpa1 and Trpm8 to Cold Allodynia and Neuropathic Pain

Cold allodynia is a common symptom of neuropathic pain. However, the underlying mechanisms of this enhanced sensitivity to cold are not known. TRPM8 and TRPA1 are non-selective cation channels expressed by sensory neurons that have been proposed as candidates for cold transducers. We have investigated the role of these ion channels in cold allodynia by examining their expression and function following nerve injury. We used a chronic constriction injury of the sciatic nerve to model neuropathic pain in mice. We dissected lumbar dorsal root ganglia (DRG) at 7 and 14 days post-surgery and used real-time RT-PCR, in situ hybridization, immunohistochemistry and calcium microfluorimetry to examine the expression and function of TRPM8 and TPRA1 after nerve injury. We found no gross change in the expression level or profile of TRPM8. However the number of cells expressing TRPA1 was reduced and shifted towards peptidergic nociceptors following injury. We also examined functional properties of cold transduction using calcium imaging. Our experiments revealed a down-regulation of TRPA1 in the DRG after nerve injury, although no change in the number of cold responsive neurons.