ABSTRACT
We have demonstrated that human epidermal keratinocytes express the /l-opiate receptor at both the mRNA and protein levels (9). The /l-opiate receptor is expressed in all layers of the epidermis. In the dermis, the receptor is expressed in the adnexal structures, especially in ducts of sweat glands, in sebaceous glands, and in the pilosebaceous unit of hair follicles. Additionally, we have shown that l3-endorphin at concentrations of about 50 nM significantly downregulates /l-opiate receptor expression and upregulates cytokeratin (CK) 16 expression in the epidermis of human skin organ cultures. The same pattern was observed in psoriatic lesional skin (i.e., /l-opiate receptor expression was significantly downregulated and cytokeratin 16 expression was upregulated). These results suggest that the /l-opiate receptor system and its ligand, l3-endorphin, are involved in the pathogenesis of psoriasis, especially in terms of differentiation. The clinical observations with opiate receptor antagonist mentioned above suggest that the opiate receptor system is also involved peripherally in the genesis of itch. Therefore, we looked into the expression of epidermal nerve endings and their colocalization with different opiate receptors and ligands in normal skin and in different pruritic skin diseases. Prurigo nodularis was chosen as a model for the pruritic state. It is an intensively chronic pruritic disorder in which persistent scratching leads to the formation of distinctive epidermodermal nodules. The histopathological features of prurigo nodularis include a dome-shaped epidermal hyperplasia, hypergranulosis, and compact hyperkeratosis. Infiltrates of inflammatory cells can vary from sparse to dense.
