Skin and hair follicle innervation in experimental models: a guide for the exact and reproducible evaluation of neuronal plasticity

The remodelling of skin innervation is an instructive example of neuronal plasticity in the peripheral nervous system. Cutaneous innervation displays dramatic plasticity during morphogenesis, adult remodelling, skin diseases and after skin nerve lesions. To recognize even subtle changes or abnormalities of cutaneous innervation under different experimental conditions, it is critically important to use a quantitative approach. Here, we introduce a simple, fast and reproducible quantitative method based on immunofluorescence histochemistry for the exact quantification of peripheral nerve fibres. Computer-generated schematic representations of cutaneous innervation in defined skin compartments are presented with the aim of standardizing reports on gene and protein expression patterns. This guide should become a useful tool when screening new mouse mutants, disease models affecting innervation or mice treated with pharmaceuticals for discrete morphologic abnormalities of skin innervation in a highly reproducible and quantifiable manner. Moreover, this method can be easily transferred to other densely innervated peripheral organs.