Altered cutaneous innervation following bleomycin administration

Abstract

Keloid patients always suffer stressful physical and psychological burdens due to intense pain. During wound healing, abnormal nerve fiber density results in altered skin sensation. However, the characteristics of cutaneous innervation in keloids and the underlying mechanisms remain unclear. Therefore, this study aims to determine whether cutaneous innervation occurs in a bleomycin-induced mouse model. Wild-type mice received intradermal bleomycin administration, a well-established model, to mimic keloids. Skin biopsies were analyzed for dermal thickness and intradermal nerve density using immunohistochemistry and immunofluorescence assays. Cutaneous neuroinflammation was evaluated using western blot analysis. Compared with phosphate-buffered saline-treated mice (saline), bleomycin-treated mice (BLM) exhibited increased dermal nerve fiber density and nociceptor expression. In addition, protein levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC) were elevated in bleomycin-treated mice, along with an increased ratio of c-caspase-1 to caspase-1. These findings suggest that the augmented cutaneous neuroinflammation potentially contributes to the enhanced cutaneous innervation in a bleomycin mouse model. Targeting the NLRP3 inflammasome in a bleomycin mouse model may reduce cutaneous reinnervation in mice.