Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human

The cloned vanilloid receptor VR1 has attracted recent attention as a molec ular integrator of painful stimuli on primary sensory neurons. The existenc e of vanilloid-sensitive neurons in the brain is, however, controversial. I n this study, we have used an antibody and a complementary RNA probe to exp lore the distribution of neurons that express VR1 in rat and in certain are as of human brain. In the rat, we observed VR1-expressing neurons throughou t the whole neuroaxis, including all cortical areas (in layers 3 and 5), se veral members of the limbic system (e.g., hippocampus, central amygdala, an d both medial and lateral habenula), striatum, hypothalamus, centromedian a nd paraventricular thalamic nuclei, substantia nigra, reticular formation, locus coeruleus, cerebellum, and inferior olive. VR1-immunopositive cells a lso were found in the third and fifth layers of human parietal cortex. Reve rse transcription-PCR performed with rat VR1-specific primers verified the expression of VR1 mRNA in cortex, hippocampus, and hypothalamus. In the cen tral nervous system, neonatal capsaicin treatment depleted VR1 mRNA from th e spinal nucleus of the trigeminal nerve, but not from other areas such as the inferior olive. The finding that VR1 is expressed not only in primary s ensory neurons but also in several brain nuclei is of great importance in t hat it places VRs in a much broader perspective than pain perception. VRs i n the brain (and putative endogenous vanilloids) may be involved in the con trol of emotions, learning, and satiety, just to name a few exciting possib ilities.