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Solving Sensitivity: In vitro Assays for Sensitive Skin

Contact Author Robert Holtz, BioInnovation Labs, Inc. Denver, U.S.
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For the complete article, click through to the October 2019 digital magazine.

Sensitive skin syndrome is a skin disorder that impacts approximately 30-55% of the world population.1 It is characterized by the manifestation of unpleasant feelings such as burning, itching, stinging, pain or prickling in the skin in response to exposure to a variety of stimuli that typically should not incite those responses.2 These stimuli can include a variety of everyday factors such as heat, cold, water or sunlight, but of specific and significant concern to our industry is that sensitive skin syndrome can be activated by exposure to topically applied products, such as cosmetics or personal health care materials. Indeed, sensitive skin syndrome (as it is known today) was first described in the mid-1980s as cosmetic intolerance syndrome3 due to the observed onset of symptoms in patients after the application of cosmetic products.

The underlying cause of sensitive skin disorder has been difficult to determine for many years. While the perceived sensory symptoms can be associated with redness or inflammation in the affected region of the skin, in the majority of cases, the individual impacted by symptoms does not display any sort of visible dermatitis or other type of observable and quantifiable symptom. Rather, the diagnosis of sensitive skin depends on the individual subjectively relaying their perceived sensory information and describing the type of skin discomfort they are feeling.

Without a firm and definite endpoint to observe, it is little wonder that it has taken a while to pinpoint the underlying mechanism for sensitive skin disorder. Over the years, various population factors have been examined, such as age, gender, hormonal status, psychological status, ethnicity and environment. In addition, many structures and components of the skin itself have been examined, including barrier function—i.e., stratum corneum thickness, water permeability and lipid content—sweat gland anatomy and epidermal innervation.4

Throughout the research, many of the examined factors were not shown to consistently contribute to sensitive skin syndrome, and slowly the list was reduced to just two main potential causative factors. The first is the barrier function of the skin, which most likely plays a role in the sensitive skin associated with some skin condition such as atopic dermatitis or acne.1 However, impaired barrier function is not a consistent observation in individuals with sensitive skin disorder, so while it may aggravate the symptoms of the disorder, it is most likely not the causative factor.5 This leaves the second factor as the current preferred mechanism to explain the underlying cause of sensitive skin syndrome: the potential dysfunction of intraepidermal nerve fibers.

The Skin as a Sensory Organ

As note, the main symptoms of sensitive skin syndrome are pain (stinging, burning, tingling or prickling sensations) and itch. These types of sensations are detected by intraepidermal nerve fibers, which include C-fibers and Aδ-fibers. These nerve fibers are unmyelinated in the epidermis—C-fibers are unmyelinated, while Aδ-fibers lose their myelination when they enter the epidermis—allowing them to come into direct contact with all epidermal cells, especially keratinocytes.6 In order for these nerve cells to perform their job of gathering sensory information, they need a means to interact with the environment. This means is provided by a class of sensory receptors belonging to the family of Transient Receptor Protein (TRP) ion gates, specifically TRPV1 and TRPV4 (for more on this topic, see Apone). It is of interest to note that these receptors are designed to specifically react directly or indirectly to stimuli that can cause pain (i.e., low pH, capsaicin, heat and UVB) or itch (i.e., histamine and endothelin-1).2 As the sensations of pain and itch are the same sensations associated with sensitive skin syndrome, then the involvement of intraepidermal never fibers, whose job it is to relay those same sensations as part of the underlying pathology, makes sense.

But there is a catch…

It has been observed that in individuals with sensitive skin syndrome, there is a hyperactivity in the intraepidermal nerve fibers associated with a lower threshold needed to activate the TRP receptors.7, 8 However, there is also an observed decrease in the density of the intraepidermal nerves within the epidermis.9 Basically, sensory nerves are more easily stimulated in sensitive skin, but there are fewer nerves present per area of the skin...

Continue reading in the October 2019 digital magazine...

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