Influence of TRPVI on diabetes-induced alterations in thermal pain sensitivity

A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN). The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ)-induced and transgene-mediated murine models of type 1 diabetes (TID), we demonstrate that Transient Receptor Potential Vanilloid I ( TRPVI) expression varies with the neuropathic phenotype. We have found that both STZ- and transgene-mediated TID are associated with two distinct phases of thermal pain sensitivity that parallel changes in TRPVI as determined by paw withdrawal latency (PWL). An early phase of hyperalgesia and a late phase of hypoalgesia are evident. TRPVI-mediated whole cell currents are larger and smaller in dorsal root ganglion (DRG) neurons collected from hyperalgesic and hypoalgesic mice. Resiniferatoxin (RTX) binding, a measure of TRPVI expression is increased and decreased in DRG and paw skin of hyperalgesic and hypoalgesic mice, respectively. Immunohistochemical labeling of spinal cord lamina I and II, dorsal root ganglion ( DRG), and paw skin from hyperalgesic and hypoalgesic mice reveal increased and decreased TRPVI expression, respectively. A role for TRPVI in thermal DPN is further suggested by the failure of STZ treatment to influence thermal nociception in TRPVI deficient mice. These findings demonstrate that altered TRPVI expression and function contribute to diabetes-induced changes in thermal perception.