Expression of PAR2 (raw data).

Background
Scabies is a debilitating parasitic skin disease caused by the obligate parasitic mite Sarcoptes scabiei, which inhabits the upper layers of the epidermis. In over 90% of affected individuals intense itching is the primary clinical symptom. This is accompanied by other delayed-type hypersensitivity responses. Persistent scratching due to the itch compromises skin integrity, facilitating the entry of pathogenic bacteria. Combined with immune-modulatory factors secreted by the mites, this creates a permissive environment for bacterial colonisation often leading to secondary complications. Effective treatment of scabies-associated itch could significantly reduce these complications and improve patients’ quality of life. However, current antipruritic therapies are inadequate: in most cases, antihistamines provide little relief for scabies-related itch, and systemic corticosteroids are generally contraindicated. Thus, there is a critical need for targeted therapies, yet progress has been hindered by a limited understanding of the underlying pathobiology of scabies-induced pruritus.
Methodology/Principal Findings
We investigated the expression of itch-associated mediators - encompassing both histaminergic and non-histaminergic pathways - using immunohistochemistry in a porcine scabies model. Skin biopsies were collected at multiple time points during the course of infection. We observed upregulated expression of key non-histaminergic itch receptors PAR-2 and MRGPRX2, as well as the mediator tryptase, following infection. Additionally, levels of the pruritogenic cytokine IL-31 and periostin, a molecule that may promote IL-4, IL-13 and IL-31 expression were elevated, as were substance P and its receptor NK-1R. In addition, the expression of histamine, the primary mediator of the histaminergic itch pathway, was also increased. Notably, reduced expression of β tubulin III across all time points suggests direct mite-induced neuroinflammation. Our findings may serve as a valuable basis for future drug development efforts focused on specific treatment of scabies-associated itch.
Conclusions/Significance
Our data suggest that both the histaminergic and non-histaminergic pathways may be involved in scabies itch. Further research is needed to better understand the complex interplay between these pathways and to identify therapeutic targets for scabies-related itch.