Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X(3) purinoceptor and IB4 binding sites

The vanilloid receptor (VR1) protein functions both as a receptor for capsa icin and a transducer of noxious thermal stimuli. To determine the expressi on and targetting of this protein, we have generated antisera against both the amino and carboxy termini of VR1. Within the dorsal roof and trigeminal ganglia of rats VR1-immunoreactivity (VR1-ir) was restricted to small and medium sized neurons. VRI-ir was transported into both the central and peri pheral processes of these primary afferent neurons, as evidenced by: (i) th e presence of VR1-ir in nerve fibres and terminals in lamina I and lamina I I of the superficial dorsal horn, and the association of VRI-ir with smalt 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 VR 1-ir proximal to sciatic nerve ligation. At the ultrastructural level, VR1- ir was associated with plasma membranes of neuronal perikarya in dorsal roo t ganglia and nerve terminals in the dorsal horn. VR1-ir was also seen in n erve fibres and terminals in the spinal trigeminal nucleus and nucleus of t he solitary tract. Within a large proportion of dorsal root ganglion neuron s and the terminals of their axons, VR1-ir was colocalized with staining fo r the P2X(3) purinoceptor, and with binding sites for the lectin IB4. Surpr isingly, VR1-ir did not coexist substantially in nerve fibres and terminals that contain substance P and calcitonin gene-related peptide, suggesting c omplex mechanisms for the release of these neuropeptides in response to cap saicin application.