Title: Possible Roles of Epidermal Opioid Systems in Pruritus of Atopic Dermatitis
Abstract: The μ-opioid (β-endorphin/μ-opioid receptor) and κ-opioid (dynorphin A (DynA)/κ-opioid receptor) systems play pivotal roles in the modulation of pruritus in the central nervous system. The μ-opioid system has also been identified in human epidermis, raising the possibility that the system controls the peripheral itch. However, the precise distribution of the κ-opioid system has not yet been clarified in human epidermis. To address this issue, reverse transcription-PCR and immunohistochemical analyses were performed on cultured keratinocytes and normal skins from humans. The analyses revealed that epidermal keratinocytes express κ-opioid receptor and its ligands, DynA (1–17) and DynA (1–8). Moreover, expression for μ- and κ-opioid systems was examined immunohistochemically in skin biopsies from healthy volunteers and patients with atopic dermatitis (AD) before and after psoralen-ultraviolet A (PUVA) therapy. Our expression analyses showed that only the κ-opioid system, not the μ-opioid system, was downregulated in the epidermis of AD patients. The downregulation of the μ-opioid system and the restoration of the κ-opioid system by PUVA therapy were observed in the AD patients, concomitant with a decrease of VAS (visual analogue scale) scores. These results suggest epidermal opioid systems are associated with the modulation of pruritus in AD. This new finding may help us to understand the control mechanism of peripheral itch. The μ-opioid (β-endorphin/μ-opioid receptor) and κ-opioid (dynorphin A (DynA)/κ-opioid receptor) systems play pivotal roles in the modulation of pruritus in the central nervous system. The μ-opioid system has also been identified in human epidermis, raising the possibility that the system controls the peripheral itch. However, the precise distribution of the κ-opioid system has not yet been clarified in human epidermis. To address this issue, reverse transcription-PCR and immunohistochemical analyses were performed on cultured keratinocytes and normal skins from humans. The analyses revealed that epidermal keratinocytes express κ-opioid receptor and its ligands, DynA (1–17) and DynA (1–8). Moreover, expression for μ- and κ-opioid systems was examined immunohistochemically in skin biopsies from healthy volunteers and patients with atopic dermatitis (AD) before and after psoralen-ultraviolet A (PUVA) therapy. Our expression analyses showed that only the κ-opioid system, not the μ-opioid system, was downregulated in the epidermis of AD patients. The downregulation of the μ-opioid system and the restoration of the κ-opioid system by PUVA therapy were observed in the AD patients, concomitant with a decrease of VAS (visual analogue scale) scores. These results suggest epidermal opioid systems are associated with the modulation of pruritus in AD. This new finding may help us to understand the control mechanism of peripheral itch. atopic dermatitis β-endorphin dynorphin A κ-opioid receptor μ-opioid receptor normal human epidermal keratinocyte prodynorphin proopiomelanocortin psoralen-ultraviolet A reverse transcription-PCR visual analogue scale