Coexistence and upregulation of three types of opioid receptors, mu, delta and kappa, in human hypertrophic scars.

ABSTRACT

BACKGROUND: Pruritus or nociceptive pain is a significant clinical problem of hypertrophic scars. Recently emerging evidence has indicated the possible involvement of opioid receptors (ORs) in abnormal cutaneous sensation; however, little is known about the pathophysiological role of ORs in local cacaesthesia in hypertrophic scars. OBJECTIVES: To study the expression profile of ORs in normal human skin and hypertrophic scars with cacaesthesia. METHODS: Skin biopsy was performed in 10 patients newly diagnosed as having hypertrophic scars with cacaesthesia, and in 10 healthy individuals. Parts of these skin tissues were subjected to primary culture of keratinocytes and fibroblasts. Localization of ORs was examined by immunofluorescence staining and quantitation of ORs was performed by real-time polymerase chain reaction (PCR). RESULTS: Immunofluorescence staining revealed that OR types mu (MOR), delta (DOR) and kappa (KOR) were coexpressed and located mainly in the keratinocytes and fibroblast-like cells. Real-time PCR indicated that the expression of MOR, DOR and KOR in hypertrophic scars was enhanced in comparison with normal skin. Consistent with the results from skin biopsy, we observed enhanced expression of MOR, DOR and KOR in the cultured keratinocytes and fibroblasts derived from hypertrophic scars in comparison with those derived from normal skin. CONCLUSIONS: Our results demonstrate that expression of three types of ORs, MOR, DOR and KOR, was markedly upregulated in human hypertrophic scars, suggesting a possible link between upregulated ORs and local cacaesthesia in hypertrophic scars.