Neurovascular Aspects of Skin Neurogenic Inflammation

Abstract

Neurogenic inflammation is involved in skin inflammation. It is hypothesized that it is involved in the pathogenesis of the common chronic cutaneous vascular disorder rosacea, but the exact mechanism of action is currently unknown. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are widely expressed on primary sensory neuron endings and non-neuronal cells such as keratinocytes. Here we describe the potential for TRPV1 and TRPA1 receptors to be involved in the pathophysiology of rosacea due to their polymodal activation, including cold and hot temperature, pungent products from vegetable and spices, reactive oxygen species, and mechanical stimuli. We discuss the role of both receptors and the sensory neuropeptides that they release in inflammation and pain sensation and evidence suggesting that both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea.

Development of an in vivo target‐engagement biomarker for TRPA1 antagonists in humans

“…Because TRPA1 antagonists are not yet available for human use, we were not able to test the specificity of the response to CA for TRPA1 in humans. However, extensive preclinical experiments support this specificity and currently no evidence for species differences in CA sensitivity has been reported [12,32,33]. In line with other DBF models such as the capsaicin model, one can assume that several factors such as sex, age and body site can play a role in the response to CA.…”

“…Another unresolved question is whether the DBF response observed is due to activation of neuronal and/or vascular TRPA1. Based on preclinical findings of Aubdool et al, it seems that neuronal TRPA1 is activated, which in turn causes the release of several neuropeptides including CGRP, Substance P and prostaglandins, and are most likely to play an important role in the neurogenic inflammation reaction [12,[32][33][34]. Therefore, future research questions still to be looked into are: (1) which secondary messengers are involved in the DBF response after …”

The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin

“…Neurogenic inflammation plays a key pathogenetic role in a variety of different acute and chronic inflammatory diseases (Chiu et al, 2012). This is a basically different inflammatory mechanism compared to immune cell-mediated processes, it is often the very early initiation step even in chronic diseases including allergic contact dermatitis, atopic dermatitis, rosacea, migraine, allergic rhinitis, sarcoidosis, rheumatoid arthritis, psoriasis, asthma and COPD Anichini et al, 1997;Aubdool and Brain, 2011;B anv€ olgyi et al, 2005;Geppetti et al, 2005;O'Connor et al, 2004;Pisi et al, 2009;Raychaudhuri and Raychaudhuri, 2004;TeresiakMikołajczak et al, 2013). This triggers and remarkably augments further cellular pathways.…”

Host Peptidic Hormones Affecting Bacterial Biofilm Formation and Virulence

“…This process should be essential in atopic dermatitis [112], psoriasis [113], rosacea [114], and a large range of inflammation-related troubles [115]. The discovery of the effects of SP, CGRP, and natriuretic peptides on Gram-positive bacteria led to a new vision of neurogenic inflammation which involves the microbial skin flora as a central relay in the inflammation process but also as a potential new target for the treatment of these diseases [116].…”