Sensitive Skins May Be Neuropathic Disorders: Lessons from Studies on Skin and Other Organs

Abstract

Sensitive skin can be considered a neuropathic disorder. Sensory disorders and the decrease in intra-epidermal nerve ending density are strong arguments for small-fiber neuropathies. Sensitive skin is frequently associated with irritable bowel syndrome or sensitive eyes, which are also considered neuropathic disorders. Consequently, in vitro co-cultures of skin and neurons are adequate models for sensitive skin.

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“…Thus, it appears that these manifestations involve cutaneous nerve fibers [162][163][164] due to the overactivation of transient receptor potential (TRP)-type receptors in the skin, which leads to constant inflammation and local redness. In detail, with regard to TRP receptors, the attention should be focused on the transient receptor potential ion channels subfamily V member 1 (TRPV1) involved in neuroinflammation.…”

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“…The sensors mostly belong to the transient receptor potential (TRP) family and can be studied using various agonists and antagonists. For example, TRPV1 can elicit capsaicin-induced heat pain [9] or a histamine-induced itching sensation [10], while TRPV4 is known as a heat sensor [11]. The menthol-activated receptor TRPM8 is responsible for the detection of innocuous and noxious cooling [8,12], and the wasabi-activated receptor TRPA1 is involved in a wide panel of stimuli, including chemo-nociception [12], thermal sensations [13,14], and itch [14].…”

“…A significant correlation between SSS and small-fiber neuropathies, especially those affecting unmyelinated C-fibers, has been established [18]. A decrease in the heat-pain threshold detection is currently considered to be responsible for the hyper-reactivity of nerve endings in response to environmental factors and the induction of neuropathic pain [11]. This detection threshold directly depends on the sensor's presence and properties.…”

“…Studying the sensory perception mechanisms of sensory neurons is, therefore, essential for the better diagnosis, prevention, and treatment of sensitive skin. Nevertheless, some studies revealed that keratinocytes also express diverse sensory receptors, such as TRPV1, TRPV3, and TRPV4 [8,11,20]. Mainly expressed in keratinocytes, TRPV3 can stimulate CGRP secretion, which induces local vasodilation that plays a role in body thermoregulation [21].…”

“…Mainly expressed in keratinocytes, TRPV3 can stimulate CGRP secretion, which induces local vasodilation that plays a role in body thermoregulation [21]. The selective activation of the keratinocyte-located TRPV1 and TRPV4 sensors is sufficient to induce pain and itch, respectively [11]. It has been shown that the activation of keratinocyte TRPV1 elicits a calcium signal, leading to intraepidermal nerve-ending activation through synaptic-like contacts.…”