Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 77

Abstract

The vanilloid receptor VR‐1 is a non‐selective ligand‐gated channel, structurally related to the transient receptor potential (TRP) family of ion channels. It responds to noxious stimuli including capsaicin, heating in the noxious range, and extracellular acidification. It is able to integrate simultaneous exposure to these stimuli and is involved in different forms of tissue hypersensitivity. VR‐1 is predominantly expressed in small‐diameter neurons of rat dorsal root ganglia (DRG), which give rise to unmyelinated sensory nerve fibers, but its immunoreactivity in human nerve fibers is not known. We assessed the expression of VR‐1 in human intra‐epidermal nerve fibers (IENF) of hairy and glabrous skin and in sural nerve biopsy. Skin biopsies were taken from proximal thigh, distal leg, trunk, arm, and fingertip in 10 healthy subjects. Immunohistochemical and confocal immunofluorescence studies using polyclonal anti‐PGP 9.5 (PGP), monoclonal anti‐unique b‐tubulin (TuJ1), and polyclonal anti‐human VR‐1 antibodies were performed. Double staining studies were carried out in the following combinations: PGP‐TuJ1 and TuJ1‐VR‐1. In each site, PGP‐positive IENF showed TuJ1 labeling and, most interestingly, VR‐1 diffusely co‐localized with all TuJ1‐positive IENF. These findings indirectly demonstrated the co‐localization between VR‐1 and the panaxonal marker PGP in IENF. VR‐1 immunoreactivity was assessed in formalin fixed, paraffin‐embedded sural nerve sections from a patient without morphological signs of sensory involvement. Almost 2/3 of unmyelinated fibers showed an intense VR‐1 immunoreactivity, which was present also in smooth muscle cells of perineurial and epineurial arterioles. VR‐1 immunolabeling was absent in myelinated fibers and in part of unmyelinated fibers, which possibly represented autonomic fibers. In conclusion, we demonstrated that VR‐1 is widely expressed in somatic human unmyelinated nerve fibers. Particularly, the diffuse immunoreactivity of IENF, which are naked terminals of small‐diameter DRG sensory neurons, suggests that they are essential for selective modalities of nociception and primarily involved in neuropathic hyperalgesia.