Search

Capsaicin receptor TRPV1 is a non-selective ligand-gated channel activated by different noxious stimuli. Previous studies suggested that an increased density of TRPV1 positive axons in the skin could be involved in the pathogenesis of neuropathic pain. To investigate the expression of TRPV1 in PDN patients, skin biopsies from 6 patients with PDN and 10 controls, and sural nerve biopsies from 2 patients with PDN and 2 controls were studied using the polyclonal anti-human TRPV1 antibody. Skin nerve fibers widely expressed TRPV1 immunoreactivity. The density of TRPV1 positive dermal and intra-epidermal nerve fibers (IENF) did not differ from that obtained using the PGP 9.5 antibody (the standard marker for IEFN recognition). Confocal analysis demonstrated that TRPV1 and anti unique-tubulin-1 antibody (TuJ1) co-localized in all axons. In PDN patients IENF density was significantly reduced, but no difference in immunostaining was detectable using TRPV1, PGP 9.5 and TuJ1 antibodies. Sural nerve unmyelinated fibers and few small-myelinated fibers were intensely stained by TRPV1. DPN patients disclosed a severe reduction in unmyelinated fiber density, but residual fibers were recognized by TRPV1. These data suggest that TRPV1 is widely expressed in skin and sural nerve unmyelinated axons, but its expression is not increased in PDN. Other mechanisms, such as changes in proximal axon or neuron excitability, are more likely involved in the pathogenesis of neuropathic pain in diabetic neuropathy. [ABSTRACT FROM AUTHOR]