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

Abstract

Sympathetic and sensory neurons form distinct axonal arborizations in several peripheral targets. The developmental mechanisms responsible for partitioning sympathetic and sensory axons between potential target tissues are poorly understood. We have used rodent footpads to study this process because three populations of peripheral axons innervate topographically segregated targets in the footpad; cholinergic sympathetic axons innervate sweat glands, noradrenergic sympathetic axons innervate blood vessels, and sensory axons form a plexus at the epidermal/dermal junction. To examine how nerve growth factor (NGF), a trophic and survival factor for sympathetic and some sensory neurons, may contribute to the generation of the patterned distribution of axons among targets, we studied transgenic mice (K14-NGF mice) in which NGF expression was significantly increased in the epidermis. Whereas the temporal sequence in which sensory and sympathetic fibers arrived in the footpad was not affected, the normal partitioning of axons between target tissues was disrupted. The two sympathetic targets in footpads, sweat glands, and blood vessels lacked substantial innervation and instead a dense plexus of catecholaminergic sympathetic fibers was found commingled with sensory fibers in the dermis. Those sympathetic fibers present in sweat glands expressed an abnormal dual catecholaminergic/cholinergic phenotype. Our findings indicate that overexpression of NGF in skin interferes with the segregation of sensory and sympathetic axonal arbors and suggests a role for target-derived NGF in the establishment of distinct axonal territories. Our data also suggest that by determining where axon arbors form, NGF can indirectly influence the phenotypic properties of sympathetic neurons.

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

“…This is consistent with the idea that NGF functions as a target-derived trophic factor capable of stimulating or modulating neuronal development, growth, and survival (41). It is also consistent with the findings from several different tissue-specific NGF transgenic mouse lines, in which NGF overexpression in pancreatic islets, pulmonary airways, skin, heart, brain, and smooth muscle resulted in the common phenotypic finding of increased sprouting by sympathetic efferent and sensory afferent nerve fibers to target organs and in many cases associated ganglion (2,20,27,28,36,37,39,45,46,104).…”

“…Anti-NGF treatment attenuated collateral sprouting into the DRG and pain-related behaviors in nerve injury-induced models of neuropathic pain (86). Transgenic mice overexpressing NGF in the skin (2,20,36) or glia (45,104) develop a similar pattern of sympathetic sprouting into target tissues and sensory ganglia, and GFAP-NGF mice showed enhanced thermal and mechanical hypersensitivity, as well as sympathetic sprouting following neuropathic nerve injury (87). Thermal hyperalgesia induced by intradermal NGF in the hindpaw was also partially dependent on sympathetic postganglionic axons (5).…”

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

“…Sympathetic innervation of target organs has been analysed in detail in footpads (Guidry et al 1998). The temporal sequence of footpad innervation is not affected in the NGF-overexpressing animals.…”

Prevention of Irritant Contact Dermatitis among Health Care Workers by Using Evidence-Based Hand Hygiene Practices: A Review

“…by frequent wet work [19][20][21][22] alcohol may penetrate more easily into the epidermis and even into the dermis. Yet in the epidermis there are interoceptors [23][24][25] which are stimulated by the alcohol, resulting in a burning sensation, but not in further irritation 11) . The problem of burning sensations tends to be the pre-irritated skin, leading to an impaired epidermal barrier, rather than the irritation caused by alcohol, which is somewhat of an old myth 26) .…”