There is increasing evidence for an intimate interaction of the skin and the nervous system. As known from animal studies, nerve growth factor (NGF) is essential for the innervation density and functional properties of sensory neurons of the skin during embryogenesis and in adulthood, and possibly during cutaneous inflammation. This study examined NGF content and sprouting of nerves during the elicitation phase of contact allergy in human skin. Skin biopsies from patients (n=14) undergoing patch-testing were taken from positive test sites and control back skin 96 h after antigen application. NGF content was measured by enzyme-linked immunofluorescence assay. Immunohistochemistry was performed for protein gene product 9.5 (PGP9.5), a marker that stains all neuronal elements, and growth-associated protein 43 (GAP43), a marker for axonal growth cones. The NGF content was significantly increased in lesional skin in comparison with normal skin (4.2+/-0.6 pg to 2.9+/-0.5 pg NGF per mg wet weight). The length of epidermal PGP9.5-immunoreactive (ir) fibers in lesional skin significantly increased from 3.4+/-0.9 mm in normal skin to 5.3+/-1.0 mm in contact eczema, whereas dermal fibers were unaltered (11.1+/-2.7 mm vs 9.5+/-2.1 mm, respectively). GAP43-ir nerve endings were significantly increased in both epidermis (1.6+/-0.3 mm to 2.6+/-0.4 mm) and dermis (0.5+/-0.1 mm to 1.8+/-0.2 mm) in contact eczema. Thus, we have provided evidence for an NGF-mediated nerve-fiber sprouting in human contact eczema. This may have a functional impact on skin-associated immune cells, in particular mast cells and Langerhans cells.

In this study, we provide evidence that botulinum toxin A is an effective and safe treatment for frontal hyperhidrosis.

Mice lacking the major Schwann cell myelin component P0 show a severe dysmyelination with pathological features reminiscent of the Déjérine-Sottas syndrome in humans. Previous morphological and electrophysiological studies on these mice did not only demonstrate a compromised myelination and myelin maintenance, but were suggestive of an impairment of axons as well. Here, we studied the axonal pathology in P0-deficient mice by quantitative electron microscopy. In addition, we investigated epidermal receptor end organs by immunocytochemistry and muscle pathology by histochemistry. In proximal sections of facial and femoral nerves, axon calibers were significantly reduced, whereas the number of myelin-competent axons was not diminished in 5- and 17-month-old P0-deficient mice. However, in distal branches of the femoral and sciatic nerve (digital nerves innervating the skin of the first toe) the numbers of myelin-competent axons were reduced by 70% in 6-month-old P0-deficient mice. Immunolabeling of foot pads revealed a corresponding loss of Merkel cells by 75%, suggesting that survival of these cells is dependent on the presence or maintenance of their innervating myelinated axons. In addition, quadriceps and gastrocnemius muscles showed pathological features indicative of denervation and axonal sprouting. These findings demonstrate that loss of an important myelin component can initiate degenerative mechanisms not only in the Schwann cell but also in the distal portions of myelinated axons, leading to the degeneration of specialized receptor end organs and impairment of muscle innervation.

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