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Isatis tinctoria L. (woad) has been used in medicine for centuries and has demonstrated anti-inflammatory effects. However, to date, no well-defined extracts with precise analysis of active substances have been developed. The aim of this study was to develop novel extracts of Isatis tinctoria L., and to characterize their active ingredients and anti-inflammatory properties. Various extracts of Isatis tinctoria L. were analysed for their active ingredients, and screened for anti-inflammatory effects using cyclooxygenase-2 activity assays. A petroleum ether extract was found to have the best effects, and was tested in a mouse model of acute allergic contact dermatitis. In the mouse model the petroleum ether extract resulted in significantly reduced ear swelling, oedema and inflammatory cell density. In mouse skin and human keratinocyte cultures, petroleum ether extract inhibited pro-inflammatory cytokine expression. Furthermore, human mast cell degranulation was significantly inhibited in LAD2 cell cultures. In conclusion, novel woad extracts were developed and shown to have anti-inflammatory properties in a contact hypersensitivity animal model and human keratinocytes. The production of such extracts and further characterization of their specific properties will enable determination of their potential dermatological effects in the treatment of inflamed and irritated skin. [ABSTRACT FROM AUTHOR]

Chronic pruritus (CP) is often accompanied by paresthetic sensations like warmth, burning and stinging. The aim of this study was to analyze, whether divergent sensations are linked to structural and functional skin alterations in clinically diagnosed CP patients. Clinical responses to capsaicin, histamine, and to thermal and mechanical stimulation, intraepidermal nerve fiber density, and epidermal expression of transient receptor potential (TRP)-channels were investigated in healthy controls, and in CP patients, reporting either warmth (CP-W) or neuropathic sensations (CP-N). In CP-W, pinprick hyperalgesia and increased sensitivity to capsaicin were aligned with increased epidermal TRPV1 expression, while smaller histamine axon reflex erythema matched with significantly reduced intraepidermal nerve fiber density. CP-N showed earlier onset of sensations after capsaicin stimulation, significantly increased warmth detection threshold, and higher epidermal expression of TRPV4 compared to healthy controls. The present study contributes to the neurobiological understanding of the divergence of sensory sensations in CP, indicating new treatment targets. [ABSTRACT FROM AUTHOR]

Chronic pruritus is difficult to treat. Current treatment options are frequently ineffective and new therapeutic approaches are urgently needed. Avenanthramides are active substances in oats that exhibit anti-inflammatory effects. Their potential to interrupt pruritus mechanisms was investigated in this study. It was found that the synthetic analog dihydroavenanthramide D (DHAvD) can interact with the neurokinin-1 receptor (NK1R) and inhibit mast cell degranulation. DHAvD also affects inflammatory processes and reduces secretion of the cytokine interleukin-6. Our findings indicate that DHAvD may act as a NK1R inhibitor and could be a promising candidate for topical treatments of chronic pruritus. [ABSTRACT FROM AUTHOR]

The complex nature and difficult-to-establish aetiology of chronic pruritus (CP) makes it challenging to provide medical care for patients with CP. This challenge can only be met with a multidisciplinary approach. The first multidisciplinary Itch Centre in Germany was established at the University of Münster in 2002 to meet the needs of this patient population. More than 2,500 outpatients and 400 inpatients are diagnosed and receive treatment each year. To ensure evidence-based medical care, an electronic system for medical documentation and patient-reported outcomes was established. Automated data transfer to a research database enables comprehensive data analysis. Our translational research has characterized peripheral and central itch mechanisms, provided novel clustering of CP patients, and identified novel target-specific therapies (e.g. neurokinin 1 receptor-antagonist). The multidisciplinary approach, combined with basic, clinical and translational research, enables comprehensive medical care of patients as well as implementation of high-quality experimental and clinical studies. [ABSTRACT FROM AUTHOR]

Background: In the treatment of atopic dermatitis, pimecrolimus has high antipruritic effects. Objective: To investigate the efficacy of 1% pimecrolimus cream in comparison to 1% hydrocortisone cream in non-atopic prurigo nodularis (PN). Methods: A randomized, controlled, double-blind study with intraindividual randomization was done in 30 patients (17 females, 13 males; mean age 58.5 years) with PN. Results: Pruritus intensity decreased significantly (p < 0.001) on both treated sides as early as after 10 days of treatment; scratch lesions improved (p < 0.001). Quality of life as assessed by the Dermatology Life Quality Index improved significantly. However, a significant advantage of pimecrolimus over hydrocortisone was not found. Conclusion: The results suggest that the non-steroid pimecrolimus is an effective alternative for PN treatment. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic pruritus is frequently refractory to currently available treatments. Studies suggest that pruritus may arise from an imbalance of the mu- and kappa-opioid receptor system activity in either the skin or the central nervous system. Stimulation of kappa-opioid receptors by their agonists inhibits pruritus in both animals and humans. The antipruritic effect of kappa-opioid receptors agonists can currently be assumed to be related to their binding to kappa-opioid receptors on keratinocytes and cutaneous and/or central itch neurones. To date, several case reports and 2 controlled trials have demonstrated a beneficial effect of systemic kappa-opioid receptor agonists in the treatment of uraemic pruritus, prurigo nodularis, paraneoplastic and cholestatic pruritus. Nalfurafine hydrochloride (Remitch®), a selective kappa-opioid receptor agonist, is approved for the treatment of chronic pruritus in Japan. The aim of this review is to provide an overview of the promising role of kappa-opioid receptors and their agonist in the pathophysiology and treatment of pruritus. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pruritus (CP), defined as itch lasting for > 6 weeks, is a burdensome symptom of several different diseases, dermatological and systemic, with a high negative impact on the quality of life of patients. Given the manifold aetiologies of CP, therapy is often difficult. In recent years, however, novel substances have been developed for treatment of certain CP entities and identified targets., Areas Covered: In this review, the authors present a survey of targets currently believed to be promising (H4R, IL-31, MOR, KOR, GRPR, NGF, NK-1R, TRP channels) and related investigational drugs that are in the preclinical or clinical stage of development. Some substances have already undergone clinical testing, but only one of them (nalfurafine) has been licensed so far. Many of them are most likely to exert their effects on the skin and interfere there with the cutaneous neurobiology of CP., Expert Opinion: Currently, the most promising candidates for new therapeutic agents in CP are neurokinin-1 receptor antagonists and substances targeting the kappa- or mu-opioid receptor, or both. They have the potential to target the neuronal pathway of CP and are thus of interest for several CP entities. The goal for the coming years is to validate these concepts and move forward in developing new drugs for the therapy of CP.

Background: In the treatment of atopic dermatitis, pimecrolimus has high antipruritic effects., Objective: To investigate the efficacy of 1% pimecrolimus cream in comparison to 1% hydrocortisone cream in non-atopic prurigo nodularis (PN)., Methods: A randomized, controlled, double-blind study with intraindividual randomization was done in 30 patients (17 females, 13 males; mean age 58.5 years) with PN., Results: Pruritus intensity decreased significantly (p < 0.001) on both treated sides as early as after 10 days of treatment; scratch lesions improved (p < 0.001). Quality of life as assessed by the Dermatology Life Quality Index improved significantly. However, a significant advantage of pimecrolimus over hydrocortisone was not found., Conclusion: The results suggest that the non-steroid pimecrolimus is an effective alternative for PN treatment.