Destruction by anti‐NGF of autonomic, sudomotor neurones and subsequent hyperinnervation of the foot pad by sensory fibres

Abstract

Treatment of newborn rats with antiserum to nerve growth factor (NGF) for the first 6 postnatal days produced a loss of the sympathetic neurones that normally project to the sweat glands of the hind paws of the rat, indicating that cholinergic sympathetic neurones require NGF postnatally for their survival. Following this immunosympathectomy, there was an increase in the proportion of glands containing sensory fibres having substance-P-like immunoreactivity (SP-LI). This sensory sprouting was not as extensive as that after sympathectomy using 6-hydroxydopamine (6-OHDA). During normal development, fibres showing SP-LI are associated with the glands, particularly during the first and second postnatal weeks. Prolongation of the antibody treatment until the third postnatal week reduced the sensory fibre ingrowth from the region of the glands, suggesting that the basis of this growth is the increased availability of NGF following sympathetic denervation. Retrograde cell labelling using the fluorescent dye, fast blue, indicated that the anti-NGF treatment did not significantly decrease the number of sensory neurones projecting to an individual foot pad. These results support the hypothesis that sympathetic and sensory neurones compete for NGF produced by target tissues.

Overexpression of nerve growth factor in epidermis disrupts the distribution and properties of sympathetic innervation in footpads

“…Second, NGF levels are correlated with the density of sympathetic axonal arbors, increased levels of NGF increase sympathetic axon density and NGF causes preterminal axons to branch (Korsching and Thoenen, 1983;Shelton and Reichardt, 1984;Edwards et al, 1989;Hoyle et al, 1993;Albers et al, 1994;Campenot, 1994;Davis et al, 1996). Third, NGF is a required survival factor for sympathetic neurons (Chun and Patterson, 1977;Gorin and Johnson, 1979;Levi-Montalcini, 1987;Crowley et al, 1994), including those that innervate sweat glands (Landis et al, 1985;Hill et al, 1988). Expression of the K14-NGF transgene results in significantly increased availability of NGF in keratinized epithelia of skin (Albers et al, 1994).…”

“…Several observations are consistent with this scenario. First, in the absence of sympathetic axons, sensory axons innervate sweat glands (Yodlowski et al, 1984;Hill et al, 1988). Second, in tabby mutant mice, which lack sweat glands but otherwise exhibit normal footpad development, sensory axons form a typical plexus at the epidermal/dermal border, but sympathetic axons grow only to the presumptive gland region (Guidry and Landis, 1995).…”

“…In the absence of sympathetic innervation, substance P (SP)-and CGRPimmunoreactive sensory fibers sprout into the glands, presumably because of the availability of NGF, which is no longer removed from the glands by sympathetic axons. The sympathetic innervation of sweat glands can also be ablated by treatment of neonatal rats with anti-NGF (Landis et al, 1985;Hill et al, 1988) and in some instances, the glands were subsequently innervated by sensory axons (Hill et al, 1988). These studies suggest that the distribution of cutaneous sensory and sympathetic fibers can be influenced by competition for NGF, raising the possibility that NGF normally contributes to the developmental segregation of sympathetic and sensory axons between their respective targets.…”

Long‐term sensory hyperinnervation following neonatal skin wounds

“…The response to adult wounds was weak and transient in comparison. Other types of sprouting response in sensory neurons, such as collateral sprouting following peripheral nerve section or sympathectomy, is also more dramatic following neonatal rather than adult intervention (Kinnman and Aldskogius, 1986;Hill et al, 1988;Fitzgerald et al, 1987;Reynolds and Fitzgerald, 19921, and this is presumably because they are still in a state of active growth in the postnatal period. Primary sensory neurons continue to express the growth-associated protein, GAP-43, mRNA until the second postnatal week (Chong et al, 19921, and the pattern and density of cutaneous arborizations undergo considerable reorganization over that period (Fitzgerald, 1966;Payne et al, 1991;Reynolds et al, 1991).…”

Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA

“…Reciprocal relationships between sympathetic and sensory nerves are thought to be mediated by changes in the availability of NGF in the target (Kessler et al 1983;Korsching and Thoenen 1985;Hill et al 1988;Schicho et al 1998), and several studies have shown that pharmacological and surgical denervation as well as nerve lesions and tissue culture elicit an increase in NGF protein levels in the targets of NGF-responsive neurons (reviewed by Rush et al 1995). Sympathectomy-induced increases in NGF protein are thought to result from altered synthesis and/or protein accumulation, due to the absence of uptake by nerves.…”