Capsaicin, the pungent substance in hot peppers, evokes a sensation of burning pain by stimulating the vanilloid receptor 1 (VR1) on primary afferent neurons. Immunohistochemistry revealed that the taste papillae in the tongue and palate are richly innervated by VR1-immunoreactive nerve fibers. Furthermore, VR1 protein expression was seen in the epithelium facing the oral cavity, although taste cells seemed to be devoid of VR1. The most conspicuous VR1 expression was observed in the epithelial cells of the palatal rugae, although there were no VR1-immunoreactive nerves there. The finding that VR1 is expressed not only in primary afferents but also in oral epithelial cells suggests that it is of great importance in the perception of capsaicin, heat, and acid in the mouth. Since VR1 is known to play a key role in nociception and inflammatory pain, it may be a new target for the treatment of oral pain.

The distribution and fine structure of nerve fibers containing neuropeptide Y (NPY), tyrosine hydroxylase (TH), and vasoactive intestinal polypeptide (VIP) in the temporomandibular joint were investigated by both the avidin-biotin complex method and an indirect immunofluorescence technique. The innervation pattern of NPY- and TH-positive fibers differed from that of VIP-positive fibers. Specifically, the former was distributed in both the superficial and deep sublining layers, while the latter was mostly located in the deep sublining layer. NPY- and TH-immunoreactive fibers were largely confined to vascular elements; occasional fibers were observed in the synovial lining layer close to the joint cavity. More nerves with NPY and TH immunoreactivity were observed close to the upper joint compartment than near the lower compartment NPY and TH immunoreactivity was dramatically reduced in the TMJ of superior cervical ganglionectomized animals, indicating the sympathetic origin of these nerves. NPY immunoreactivity was found only in unmyelinated axons, which were located in the adventitia and adventitia-medial border of arteries or arterioles. Occasionally, axons were near the joint cavity, in areas free of vascular structures. These observations show that abundant sympathetic nerves supply the temporomandibular joint of the rat and provide a morphological basis for the involvement of different neuropeptides in vascular regulatory and modulatory functions in physiological and pathophysiological conditions.