Analgesic and antipruritic effects of oxymatrine sustained-release microgel cream in a mouse model of inflammatory itch and pain

Abstract

BackgroundAllergic contact dermatitis (ACD) is a highly prevalent inflammatory and immune skin disease accompanied with persistent pruritus and pain. Oxymatrine (OMT) exhibits antipruritic and anti-inflammatory effects in squaric acid dibutyl ester (SADBE) induced ACD mice model, but the need for frequent administration stipulated by short half-life and low bioavailability limits clinical application. ObjectiveTo evaluate the analgesic and antipruritic effects of OMT gel (OG), OMT sustained release microgel powder (OMP) and OMT sustained release microgel cream (OMC) in SADBE induced ACD mice, with subsequent study of the mechanism and side effects (irritation) of optimal dosage form. MethodOn day 11, the thickness of the right cheek skin of mice was measured and mice spontaneous behaviors were recorded for 1.5 h. In the OMC experiment, hematoxylin-eosin and toluidine blue staining were performed on the cheek skin, and the irritation of OMC was tested on the back skin of rabbits. Blood analyzer was used to measure the counts of inflammatory cells in peripheral blood. The mRNA expressions of IL-1β, TNF-α, CXCR3, CXCL10, IL-6, IL-10, IL-17A and IL-31 in cheek skin, TRPA1 and TRPV1 channels in trigeminal ganglion (TG), IFN-γ in spleen and IL-17A in thymus were measured by RT-qPCR. ResultsOMC, OMP and OG significantly decreased wipes and scratching bouts, alleviated skin inflammation. OMC required less frequent administration and is easier to apply, while its antipruritic effect was stronger than the analgesic effect. OMC rescued the deficits in epidermal keratinization and inflammatory cell infiltration, decreased the leukocyte count in peripheral blood, had no irritation to the broken rabbit's skin. Furthermore, OMC significantly down-regulated the mRNA expression of IL-1β, TNF-α, CXCR3, CXCL10, IL-6, IL-10, IL-17A and IL-31 in cheek skin, TRPA1 and TRPV1 channels in TG, IFN-γ in thymus and IL-17A in spleen. ConclusionWe have demonstrated that OMC exhibits advanced analgesic, antipruritic and anti-inflammatory effects when compared with OG and OMP in ACD mice by regulating inflammation, chemokines, immune mediators and inhibiting the mRNA expression of TRPA1 and TRPV1. OMC has no irritation to the intact and damaged skin of rabbits.