Effects of capsaicin-induced sensory denervation on osteoclastic resorption in adult rats

in various clinical (Chantraine et al. 1986) and experimental (Hill et al. 1993) situations.A neural involvement in bone metabolism is possible through the dense network of nerve fibres innervating the periosteum, the bone marrow and the osteochondral junction of the growth plate (Bjurholm et al. 1988; Hill & Elde, 1991;Hukkanen et al. 1992).Also, neuromediators mediate osteoclastic resorption: vasoactive intestinal polypeptide (VIP) activating (Rahman et al. 1992) and calcitonin generelated peptide (CGRP) inhibiting (D'Souza et al. 1986) it.Moreover bone cells bear specific receptors for CGRP, VIP and neuropeptide Y (Bjurholm et al. 1992;Rahman et al. 1992).Both the sensory and sympathetic nervous systems appear to be involved in the control of mechanically driven bone resorption (Sandhu et al. 1987; Hill et al. 1991;Cherruau et al. 1999).Capsaicin, a neurotoxic agent, induces sensory denervation in developing animals by inducing the death of most small dorsal root ganglion cells and leading to a loss of unmyelinated sensory axons when administered to newborn animals (Jancso & Kiraly, 1980).Hill et al. (1991) reported a 21% reduction in bone resorption when rats treated with capsaicin at birth were subjected to a wave of synchronised resorption in adulthood.This relatively small reduction in resorption suggests either that contribution of sensory innervation to resorption is minor, or that compensatory mechanisms are involved (Hill et al. 1991).An efficient approach to test the role of the sensory system would be to chemically denervate adult animals.Capsaicin treatment of adults provokes dose-dependent sensory deficits similar to those occurring in animals treated at birth (Gamse et al. 1981).Chung et al. (1990) found that the receptive part of the peripheral sensory axons was destroyed while the cell body and most of the peripheral axon remained intact.In the present study we tested the effects of capsaicin administration to adult rats by using the same model of osteoclastic resorption as Hill et al. (1991), formerly described by Tran Van et al. (1982). METHODSWe used 30 male Wistar rats weighing 200-220 g.They were maintained on a standard rodent diet (M25 Extralabo; U.A.R., France) and water ad libitum.The study followed the European Community recommendations (86Ï609ÏEEC) on laboratory animal care.