DENTAL INNERVATION AND CGRP IN ADULT P75-DEFICIENT MICE

Adult dental tissues have unusual neurotrophin biology. Pulpal fibrobl asts express nerve growth factor (NGF) and the low-affinity p75 neurot rophin receptor, their sensory nerve fibers express p75 and trk A, and pulpal sympathetic fibers lack p75. Following tooth injury, there is increased pulpal NGF, sprouting of sensory nerve endings, and increase d immunoreactivity for the sensory neuropeptide calcitonin gene-relate d peptide (CGRP). In the present study, we have analyzed tooth structu re and innervation of pulp and periodontal ligament in young (6-8 week s, 3 months) and older (5-12 months) adult mice carrying a null mutati on in the p75 gene and compared the results with those of age-matched wild-type controls. Our hypotheses were that tooth structure would be abnormal and that pulpal innervation would be greatly reduced because it consists primarily of nociceptive fibers that have been found to be severely depleted in skin of p75(-/-) mice. Tissues were fixed, X-ray ed for gross dental morphology, decalcified, and analyzed for immunore activity for CGRP and for a general nerve marker, protein gene product 9.5. Radiographs showed worn-down molar crowns in p75-deficient mice. Light microscopy confirmed the accelerated molar wear and showed inte nse CGRP immunoreactivity in pulp nerve endings of mutant mice, compar ed with a gradual decrease in CGRP intensity in controls during normal aging. The CORP intensity in 5-12-month-old pairs of mice was threefo ld greater in the mutants (P < 0.03), and in younger mice the mutant a lways had more CGRP than its matched control. The innervation of molar ligament in all p75-deficient mice was similar to that of controls ex cept there was nerve sprouting near bone loss in mutants. The incisors of mutant mice did not have unusual wear and their pulpal CGRP immuno reactivity remained normal, but their periodontal ligament had fewer t hin branched nerve endings at all ages. Thus, most innervation of teet h and their supporting tissues developed normally, and the only neural changes in p75(-/-) mutant mice were the reduction of incisor ligamen t sensory receptors and increased molar CGRP. Sensory nerves in teeth gradually lose neuropeptide intensity during aging, but that did not h appen in the mutant mice, suggesting that the accelerated molar wear s timulated persistent high levels of CGRP. (C) 1997 Wiley-Liss, Inc.