Abstract
Pruritus is the predominant symptom of skin disease and can be defined indirectly as a sensation that leads to a desire to scratch. Patients with dry skin such as chronic renal disease and atopic dermatitis often complain of intense itching and excessive scratching. However, the precise mechanisms of itch in these diseases is poorly understood. We investigated the mechanisms and treatment of itch in these diseases. The mechanisms of itching in hemodialysis patient have not yet been fully elucidated. Recently the mu opioid system has been suggested to be one of the major pathways involved in itch sensation.
We examined the endogenous opioid system in hemodialysis patients demonstrating uremic pruritus and found that the kappa opioid system contributes to itch sensation along with the mu opioid system. A novel kappa opioid agonist TRK-820 expressed remarkable antipruritic action in antihistamine-resistant uremic pruritus patients. These findings also suggest that kappa opioid agonist is a promising antipruritic drug to treat various pruritic dieases. Pruritus is a major symptom in atopic dermatitis. Antihistamines are generally unhelpful in atopic dermatitis pruritus. In atopic dermatitis skin, increased densities of intraepidermal neurites are observed, suggesting that the neuritogenesis in the epidermis is related to itching and sensitive skin. We showed that nerve growth factors (NGF, amphiregulin) and gelatinase are involved in the elongation of nerve fibers to the epidermis. We found the abnormal expression of opioid system in epidermal keratinocytes in atopic dermatitis suggesting that the epidermal opioid system is associated with the modulation of pruritus. PUVA therapy normalized the abnormal expression of opioid system in keratinocytes and decreased densities of intraepidermal neurite formation. These findings suggest that the cause of intractable pruritus of atopic dermatitis is the increase in epidermal nerve fibers along with abnormal expression of the opioid system in keratinocytes.
