Epidermal NGF and Sema3A levels in pruritic skin samples. (a) Skin biopsies from HC and patients with AD were stained with anti-NGF antibody. Epidermal NGF levels (green) were higher in AD patients than in HC. Nuclei were counterstained with DAPI (blue). The white dotted line in each panel indicates the border between the epidermis and dermis (basement membrane). (b) Double labeling of Sema3A (green) and type IV collagen (red) in the skin of HCs and AD patients. Epidermal Sema3A levels were lower in AD patients than in HCs. Scale bars are 75 µm; epi, epidermis; der, dermis. (c) A possible regulatory model of sensory nerve fiber penetration into the epidermis by a balance of nerve elongation factors such as NGF and nerve repulsion factors such as Sema3A. Epidermal NGF levels were lower and epidermal Sema3A levels were higher in healthy skin than in atopic and dry skin, suggesting the suppression of penetration and/or elongation of nerve fibers into the normal epidermis. In contrast, epidermal NGF levels were higher and epidermal Sema3A levels were lower in atopic and dry skin than in healthy skin. This mechanism may be involved in the induction or acceleration of penetration and/or elongation of nerve fibers into normal epidermis.