Chemical sympathectomy‐induced changes in TH‐, VIP‐, and CGRP‐immunoreactive fibers in the rat mandible periosteum: Influence on bone resorption

Abstract The expression of neurotransmitter receptors by bone cells supports the concept that the nervous system is a regulator of bone metabolism. The discrimination of the respective roles of the sensory and sympathetic nervous systems requires evidence of topographic relationships between the corresponding fibers and the cells involved in bone turnover, in vivo. In this study, the influence of the sympathetic system on bone resorption was assessed by using a synchronized model of cortical resorption along the mandible. The sympathetic system was destroyed by daily injections of guanethidine (40 mg/kg) for 25 days; a resorption wave was induced on day 21. The distribution of periosteal tyrosine‐hydroxylase (TH)‐, vasoactive intestinal polypeptide (VIP)‐, and calcitonin gene‐related peptide (CGRP)‐immunoreactive (IR) fibers was studied by compartmentalizing the periosteum. Most fibers were located in the distal, non‐osteogenic compartment. TH‐IR fibers were located perivascularly, VIP‐IR fibers were gathered at the boundary with the osteogenic compartment, and CGRP‐IR fibers were scattered. Sympathectomy decreased the number of TH‐ and VIP‐IR fibers and increased the number of CGRP‐IR fibers, without changing their topography. After the injection of Fast blue, a retrograde fluorescent marker, over the periosteum, fluorescent neuronal cell bodies were found in the superior cervical ganglion (SCG). Many neurons were TH‐IR and very few were VIP‐IR. Sympathectomy decreased the numbers of fluorescent and TH‐IR cell bodies. It also decreased the number of preosteoclasts and osteoclasts, which had a drastic effect on the cortical bone surface, as assessed by scanning electron microscopy. These data indicate that VIP‐IR fibers have a strategic position close to the most peripheral and less differentiated, osteogenic cells, pointing to a functional relationship. As poorly differentiated osteogenic cells support preosteoclast differentiation, VIP‐IR fibers may be involved in this process, as suggested by the smaller number of preosteoclasts in sympathectomized rats. Although VIP is predominantly a parasympathetic mediator, it seemed to be conveyed by sympathetic fibers, as shown by the marked effect of guanethidine treatment. Nevertheless, these fibers did not originate from the SCG, contrary to TH‐IR fibers. © 2003 Wiley‐Liss, Inc.