limaprost and Pruritus

The role of prostaglandins in mechanical scratching-induced cutaneous barrier disruption in mice was investigated. Skin prostaglandins contents were measured after cutaneous barrier function was disrupted by scratching using a stainless-steal wire brush (mechanical scratching), then effects of prostanoids on recovery of cutaneous barrier functions were examined. This mechanical scratching increased transepidermal water loss and skin prostaglandins (prostaglandin D2, prostaglandin E2, 6-keto-prostaglandin F1alpha and prostaglandin F2alpha) contents, count-dependently. Topical application of indomethacin immediately after cutaneous barrier disruption delayed the recovery period of cutaneous barrier disruption. We examined effects of several prostanoids (prostaglandin D2, prostaglandin E2, prostaglandin F2alpha, prostaglandin I2 and U46619) on delay of the recovery process of mechanical scratching-induced cutaneous barrier disruption with treatment of indomethacin. Topically applied prostaglandin D2 and prostaglandin E2 accelerated the recovery of cutaneous barrier disruption and topical application of prostaglandin J2, limaprost, sulprostone and ONO-4819, but not 13,14-dihydro-15-keto-prostaglandin D2, 15-deoxy-Delta(12,14)-prostaglandin J2, 17-phenyl-trinor-prostaglandin E2 or butaprost had effects on recovery of the cutaneous barrier. These results suggest that prostaglandin D2 and prostaglandin E2 accelerate the recovery process of cutaneous barrier disruption caused by mechanical scratching, via specific prostanoid DP1, EP3 and EP4 receptors.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Heptanoates; Indomethacin; Male; Mice; Mice, Inbred BALB C; Prostaglandin D2; Pruritus; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP4 Subtype; Skin; Stress, Mechanical; Time Factors; Water Loss, Insensible

We investigated the effects of several agents on the established itching model in NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related characteristics. The number of spontaneous scratching behaviors (the duration time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before and after administration of agents for 24 h. The scratching behavior by NC/Nga mice was significantly suppressed by administration of dexamethasone or tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride. These results suggest that this method shows a good correlation with the effectiveness of drugs prescribed for itching in humans with atopic dermatitis, and histamine and serotonin do not play an important role in causing the scratching behavior seen by NC/Nga mice. The scratching behavior was also significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These results suggest that the scratching behavior seen in this model is caused by itching signal transmission through neural system. Furthermore, we found that theophylline, pinacidil or limaprost had scratching suppression effects in this model.

Topics: Alprostadil; Animals; Antipruritics; Behavior, Animal; Capsaicin; Chlorpheniramine; Cyproheptadine; Dermatitis, Atopic; Dexamethasone; Dibucaine; Male; Mice; Mice, Inbred Strains; Naloxone; Pinacidil; Pruritus; Tacrolimus; Theophylline; Time Factors