Efficacy of a skin care cream with TRPV1 inhibitor 4‐t‐butylcyclohexanol in the topical therapy of perioral dermatitis

Background Perioral dermatitis is a clinically distinctive reaction pattern of facial dermatitis, including redness, dryness, burning, pruritus and skin tightness. A gold standard treatment remains unclear. Objectives Our study evaluates the clinical value of a skin care cream with the transient receptor potential vanilloid type 1 inhibitor 4‐t‐butylcyclohexanol in POD patients over 8 weeks. Methods This open, unblinded 8‐week clinical trial included 48 patients. A skin care cream containing 4‐t‐butylcyclohexanol was applied over a period of 8 weeks. Standardized questionnaires were used at baseline, 4 and 8 weeks, for history documentation, objective and subjective severity scores, and quality of life assessments. Six different skin physiology parameters were assessed at all timepoints. Results The perioral dermatitis severity score decreased significantly during the treatment period. This was mirrored by significantly lower patients’ subjective numerical rating score and an improved quality of life score. Transepidermal water loss, stratum corneum hydration and skin erythema improved significantly during the treatment period. Conclusion This transient receptor potential vanilloid type 1 inhibitor‐based skin care cream improved subjective and objective parameters of perioral dermatitis. Decreased transepidermal water loss values and increased stratum corneum hydration demonstrate a restored skin barrier function. Consequently, the topical inhibition of these receptors is a promising management option for POD

Oxytocin modulates proliferation and stress responses of human skin cells : implications for atopic dermatitis

The neuropeptide hormone oxytocin (OXT) mediates a wide spectrum of tissue-specific actions, ranging from cell growth, cell differentiation, sodium excretion to stress responses, reproduction and complex social behaviour. Recently, OXT expression was detected in keratinocytes, but expression of its receptor and function are still unexplored in human skin. Here, we showed that both OXT and its receptor are expressed in primary human dermal fibroblasts and keratinocytes. OXT-induced dose-dependent calcium fluxes in both cell types demonstrating that the OXT receptor (OXTR) is functionally expressed. We also showed that OXT decreases proliferation of dermal fibroblasts and keratinocytes in a dose-dependent manner. In order to further investigate OXT-mediated functions in skin cells, we performed OXTR knockdown experiments. OXTR knockdown in dermal fibroblasts and keratinocytes led to elevated levels of reactive oxygen species and reduced levels of glutathione (GSH). Moreover, OXTR-depleted keratinocytes exhibited an increased release of the pro-inflammatory cytokines IL6, CCL5 and CXCL10. Our data indicate that the OXT system modulates key processes which are dysregulated in atopic dermatitis (AD) such as proliferation, inflammation and oxidative stress responses. Furthermore, we detected a downregulation of the OXT system in peri-lesional and lesional atopic skin. Taken together, these data suggest that the OXT system is a novel neuroendocrine mediator in human skin homoeostasis and clinically relevant to stressed skin conditions like AD

GABA Blocks Pathological but Not Acute TRPV1 Pain Signals

SummarySensitization of the capsaicin receptor TRPV1 is central to the initiation of pathological forms of pain, and multiple signaling cascades are known to enhance TRPV1 activity under inflammatory conditions. How might detrimental escalation of TRPV1 activity be counteracted? Using a genetic-proteomic approach, we identify the GABAB1 receptor subunit as bona fide inhibitor of TRPV1 sensitization in the context of diverse inflammatory settings. We find that the endogenous GABAB agonist, GABA, is released from nociceptive nerve terminals, suggesting an autocrine feedback mechanism limiting TRPV1 sensitization. The effect of GABAB on TRPV1 is independent of canonical G protein signaling and rather relies on close juxtaposition of the GABAB1 receptor subunit and TRPV1. Activating the GABAB1 receptor subunit does not attenuate normal functioning of the capsaicin receptor but exclusively reverts its sensitized state. Thus, harnessing this mechanism for anti-pain therapy may prevent adverse effects associated with currently available TRPV1 blockers