Capsaicin induces atopic dermatitis‐like manifestations through dysregulation of proteolytic system and alteration of filaggrin processing in rats

Abstract

Atopic dermatitis (AD) is a complex disease featuring pruritic skin inflammation. Many animal models have been developed. In a rat model, subcutaneous capsaicin injection within 48 hours after birth induces AD-like skin manifestations of dermatitis and scratching behaviour 3 weeks after the injection. When 2- to 4-week-old rats were injected with capsaicin, the lag period was shortened, and the severity of skin manifestations was significantly reduced, suggesting influences of postnatal development. Lgr6 is an epidermal stem cell marker that is normally restricted to the isthmus area of hair follicles at postnatal 2 weeks. Lgr6 persisted in the interfollicular epidermis of capsaicin-injected rats beyond 3 weeks after birth, indicating that capsaicin-induced skin manifestations were influenced by postnatal epidermal development. Capsaicin injection induced alteration of proteolytic processing of filaggrin and corneodesmosin, suggesting epidermal barrier dysfunction. Inappropriate degradation of matriptase was observed. Degrees of proteolysis of these proteins were corelated with the severity of manifestations, suggesting that inappropriate proteolysis might be a possible cause of the skin manifestations. These results strongly suggest that capsaicin may dysregulate the protease system, resulting in alteration of profilaggrin and corneodesmosin proteolysis and skin manifestations. These events may be influenced by postnatal epidermal development.

Topical film prepared with Rhus verniciflua extract‐loaded pullulan hydrogel for atopic dermatitis treatment

“…Cutaneous lesions were carefully assessed by scoring systems as previously described . Skin condition at the designated shoulder area was assessed twice, just before the initial application of pullulan hydrogel or RVE@PH (PND 42) and just after the last application (PND 56), to determine changes in the extent and severity of the lesions ( n = 5 per group).…”

“…Cutaneous lesions were carefully assessed by scoring systems as previously described. 29,36 Skin condition at the designated shoulder area was assessed twice, just before the initial application of pullulan hydrogel or RVE@PH (PND 42) and just after the last application (PND 56), to determine changes in the extent and severity of the lesions (n = 5 per group). We divided all skin lesions within 3 cm 2 of the shoulder into the inspection units (0.25 cm 2 ), inspected and scored the severity of each unit, and summed the scores per unit to yield the total score per rat individual.…”

“…To address the hypothesis, we first developed a novel topical film made up of pullulan hydrogels loaded with RVE (RVE@PH) and tested the therapeutic efficacy against AD using in vivo AD‐like experimental models. For AD modeling, we adopted the neonatal capsaicin injection method in rat neonates as previously described . Therapeutic efficacy of RVE@PH was evaluated in terms of dermatitis score, epidermal thickness, mast cell infiltration, and serum myeloperoxidase (MPO) activity, and the results were compared with that of pullulan hydrogel.…”

“…For AD modeling, we adopted the neonatal capsaicin injection method in rat neonates as previously described. [28][29][30] Therapeutic efficacy of RVE@PH was evaluated in terms of dermatitis score, epidermal thickness, mast cell infiltration, and serum myeloperoxidase (MPO) activity, and the results were compared with that of pullulan hydrogel.…”