Construction of a Modified Pain-Induced Stress White Hair Model

Resiniferatoxin (RTX) is a key tool for modelling pain-induced white hair because it induces an acute pain-related stress response. However, the specific dosage, injection method, and localization of white hair formation remain unclear. We aimed to investigate RTX application to establish a more stable mouse model of pain-induced stress-associated premature greying using a multidimensional approach. The effects of sex, age, RTX dose, depilation, and injection method on white hair location and area were investigated. Melanin granules and tyrosine-related protein 2 (TRP2)-positive cells in hair follicles were detected using histological and immunofluorescence analyses. RTX at 90 μg/kg induced the largest and most stable white hair area without inducing mortality. Male mice exhibited a higher proportion of white hair area compared to females. The proportion of white hair area was higher in 4-week-old male mice than in other age groups. Total and central activity distance ratios decreased in the open-field tests. Weight gain slowed significantly. Haematoxylin and eosin and Fontana-Masson staining revealed fewer melanin granules in the hair follicles and root areas of white hair. Immunofluorescence analysis showed a reduced TRP2-positive cell count in white hair follicles. A model of pain-induced hair depigmentation in 4-week-old male C57BL/6J mice was established by intraperitoneal injection of RTX at 90 μg/kg. Wax hair removal on day 14 accelerated white hair formation, resulting in a stable white hair area with reduced melanin granules in the follicles.