Possible roles of epidermal opioid systems in pruritus of atopic dermatitis

The p-opioid(ss-endorphin/mu-opioid receptor) and K-opioid (dynorphin A (DynA)/K-opioid receptor) systems play pivotal roles in the modulation of pruritus in the central nervous system. The mu-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 K-opioid system has not yet been clarified in human epidermis. To address this issue, reverse transcription-PCR and immumohistochernical analyses were performed on cultured keratinocytes and normal skins from humans. The analyses revealed that epidermal keratinocytes express K-opioid receptor and its ligands, DynA (1-17) and DynA (1-8). Moreover, expression for mu- and K-opioid systems was examined immunohistochemically in skin biopsies from healthy volunteers and patients with atopic dermatitis (AD) before and after psoralen-ultraviolet A (PILIVA) therapy. Our expression analyses showed that only the K-opioid system, not the mu-opioid system, was clownregulated in the epidermis of AD patients. The clownregulation of the mu-opioid system and the restoration of the K-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.