Abstract
Purpose: Pruritus without visible skin disorders is often overlooked in immobile older patients with advanced cognitive impairment who struggle to communicate their discomfort, leading to inadequate care. We investigated whether the nerve growth factor（NGF）/semaphorin（SEMA）3A ratio could serve as a biomarker for C-fiber density, aiming to develop a noninvasive evaluation method.
Methods: A dry-skin rat model was used to investigate the correlation between the C-fiber number and NGF/SEMA3A ratio in the epidermis and papillary dermis. Rats were randomized into four groups: control, acetone/diethyl ether mixture/distilled water（AEW）, cholesterol sulfate（CS）, and CS + AEW groups. C-fiber localization was evaluated through protein gene product 9.5-specific immunofluorescence staining. NGF and SEMA3A localization and expression were evaluated using immunohistochemistry and western blotting, respectively.
Results: Epidermal C-fiber number was significantly higher in the AEW group than in the other groups（p =0.008-0.013）, whereas the papillary dermis C-fiber number showed no inter-group differences. Western blotting revealed no inter-group differences in NGF/SEMA3A protein expression levels in either layer. However, a significant positive correlation was observed between the NGF/SEMA3A ratio and C-fiber number in the papillary dermis when combining all groups（ρ = 0.556; p = 0.031）.
Discussion: The inter-group differences in the epidermal C-fiber number suggests that CS promoted SEMA3A expression and suppressed C-fiber elongation into the epidermis. The positive correlation between the NGF/SEMA3A ratio and C-fiber number in the papillary dermis suggests its potential as a biomarker for C-fiber density in this layer.
