Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X₃ purinoceptor and IB4 binding sites

TLDR

The vanilloid receptor (VR1) functions as a receptor for capsaicin and transduces noxious thermal stimuli. The study aimed to determine the expression and targeting of VR1. Antisera against both the amino and carboxy termini of VR1 were generated to enable this mapping. VR1 immunoreactivity was confined to small and medium dorsal root and trigeminal ganglion neurons, transported into central and peripheral processes—including lamina I/II, skin, cornea, spinal trigeminal nucleus, and solitary tract—colocalized with P2X3 and IB4, but largely absent from substance P and CGRP‑containing fibers, and its distribution was altered by dorsal rhizotomy and sciatic nerve ligation.

Abstract

Abstract The vanilloid receptor (VR1) protein functions both as a receptor for capsaicin and a transducer of noxious thermal stimuli. To determine the expression and targetting of this protein, we have generated antisera against both the amino and carboxy termini of VR1. Within the dorsal root and trigeminal ganglia of rats, VR1‐immunoreactivity (VR1‐ir) was restricted to small and medium sized neurons. VR1‐ir was transported into both the central and peripheral processes of these primary afferent neurons, as evidenced by: (i) the presence of VR1‐ir in nerve fibres and terminals in lamina I and lamina II of the superficial dorsal horn, and the association of VR1‐ir with small diameter nerve fibres in the skin and cornea; (ii) the reduction of VR1‐ir in the spinal cord after dorsal rhizotomy; and (iii) the accumulation of VR1‐ir proximal to sciatic nerve ligation. At the ultrastructural level, VR1‐ir was associated with plasma membranes of neuronal perikarya in dorsal root ganglia and nerve terminals in the dorsal horn. VR1‐ir was also seen in nerve fibres and terminals in the spinal trigeminal nucleus and nucleus of the solitary tract. Within a large proportion of dorsal root ganglion neurons and the terminals of their axons, VR1‐ir was colocalized with staining for the P2X 3 purinoceptor, and with binding sites for the lectin IB4. Surprisingly, VR1‐ir did not coexist substantially in nerve fibres and terminals that contain substance P and calcitonin gene‐related peptide, suggesting complex mechanisms for the release of these neuropeptides in response to capsaicin application.