Topical Application of Tenshino-SoftgelTM Reduces Epidermal Nerve Fiber Density in a Chronic Dry Skin Model Mouse

Background: Dry skin induces antihistamine-resistant itch, as well as epidermal hyperinnervation, which is partly responsible for peripheral itch sensitization. In acute dry skin, topical application of emollients prevents the penetration of nerve fibers into the epidermis. However, the effects of emollients on itch and epidermal hyperinnervation in individuals with chronic dry skin are poorly understood. Objective: This study examined the effects of Tenshino-softgelTM (TSG) on itch-related behavior, epidermal hyperinnervation and skin barrier function in a chronic dry skin model mouse. Methods: Chronic dry skin was induced by application of acetone/ether (1:1) mixture and water (AEW) to the rostral parts of the back of hairless mice twice daily for six consecutive days. As treatment, TSG or, as control, Vaseline (V) was applied to the same areas twice daily. Skin barrier function was evaluated by measuring transepidermal water loss (TEWL) before each treatment. Scratching behavior was recorded and analyzed using a SCLABA®-real system, and skin samples were collected for immunohistochemical assays. Results: TEWL tended to be lower and scratching bouts fewer in AEW + TSGthan in AEW-treated mice. The numbers of protein gene product 9.5-immunoreactive fibers and substance P-immunoreactive fibers were each significantly lower in the epidermis of AEW + TSGthan of AEW-treated mice, but the expression of nerve growth factor in epidermis was similar in the three groups. Semaphorin 3A expression was significantly higher in the epidermis of AEW + TSGthan of AEWand AEW + V-treated mice. Conclusion: Topical application of TSG may attenuate itch induced by chronic dry skin through a mechanism involving the inhibition of epidermal hyperinnervation. They contributed equally to this work. Corresponding author.