Kao Identifies a Cause of Sensitive Skin

Sensitive skin that is prone to discomfort contains more nerve fibers extending deep into the stratum corneum, according to researchers at Kao.

Under the supervision of Professor Kenji Kabashima of the department of dermatology, Graduate School of Medicine, Kyoto University, that, compared to healthy skin, sensitive skin that is prone to discomfort contains more nerve fibers extending deep into the stratum corneum (Figure 1). It suggests that this could be led by dysfunction of the epidermal tight junctions, which are part of the skin’s barrier system. Kao also discovered that γ-amino-β-hydroxybutyric acid enhances the function of epidermal tight junctions in cultured keratinocytes, and has shown that continuous use, for eight weeks, of a prototype formulation containing γ-amino-β-hydroxybutyric acid decreased characteristic tingling and burning discomfort in sensitive skin.

The results of this research were presented at the 50th Convention of the Japanese Cosmetic Science Society in Tokyo, Japan (July 4–5, 2025). The presentation earned the Convention President’s Award.

A Primer on Sensitivity

Sensitive skin refers to skin that is highly sensitive and prone to uncomfortable sensations such as pain, itching and tingling in response to stimuli that would not normally trigger a reaction. Kao has for many years been researching skin that, despite the absence of skin disease, is highly sensitive to irritation. Decreased barrier function in the stratum corneum is known to be a factor in sensitive skin. Kao has been focusing on and elucidating the role of ceramides, which are major structural components of intercellular lipids in the stratum corneum.¹

The activation of neural activity is also thought to be a factor in sensitive skin, but there was insufficient progress in this field of investigation, and the detailed mechanism by which the uncomfortable sensations arise remained unclear. Kao therefore conducted new investigations focusing on nerve fibers within the epidermis.

Sensitive Skin Contains More Intraepidermal Nerve Fibers

The granular layer of the epidermis contains structures known as tight junctions, whose function is to keep neighboring cells in very close contact with each other in order to prevent invasion of foreign substances and evaporation of moisture. Another role of tight junctions is to keep nerve fibers to the inner side of the tight junctions (Figure 2), and it has been reported that in atopic dermatitis, weakening of the tight junctions allows nerve fibers to extend to just below the stratum corneum where they can cause discomfort such as itching.

In order to investigate the relationship between intraepidermal nerve fibers and hypersensitivity, which is a characteristic of sensitive skin, Kao researchers divided a group of Japanese women in their 20s to 50s into a sensitive skin group and a healthy skin group,² and compared the distribution of cutaneous nerve fibers in the skin on the inner sides of their upper arms (Figure 1). It is known that nerve fibers are usually distributed from the basal layer to the granular layer of the epidermis, and the research team has found that in sensitive skin, a significantly higher number of nerve fibers extend deep into the stratum corneum (Figure 3).

Decreased Gene Expression of Claudin-3

To investigate the mechanism by which nerve fibers extend deep into the stratum corneum in sensitive skin, the gene expression in skin tissue was comprehensively analyzed. The results revealed that gene expression of claudin-3, which is known to be a structural component of tight junctions, was significantly lower in the sensitive skin group than in the healthy skin group.

Then, to investigate whether decreased claudin-3 affects epidermal tight junction function, the transepithelial electrical resistance (TEER) value, a known indicator of barrier function, was evaluated in normal human epidermal keratinocytes wherein claudin-3 activity had been selectively weakened using genetic engineering techniques. The TEER values were significantly decreased, which shows that claudin-3 contributes to tight junction function.

This suggests that discomfort in sensitive skin is triggered by increased invasion of nerve fibers deep into the stratum corneum, presumably due to decreased epidermal tight junction function with suppressed claudin-3 expression.

The Search for Effective Raw Materials

Kao searched for cosmetic materials that enhance the function of epidermal tight junctions, with the aim of suppressing excessive extension of nerve fibers. On adding various materials to normal human epidermal keratinocytes and comparing claudin-3 expression, it was found that γ-amino-β-hydroxybutyric acid, an amino acid derivative, (Figure 4) affords significant, dose dependent increases in claudin-3 expression and TEER values.

Also, in an eight-week clinical study in 40 women in their 20s to 40s who were aware of having sensitive skin and had high sensitivity to irritation,³ the subjects were divided into a group of 20 subjects who used a prototype formulation containing γ-amino-β-hydroxybutyric acid, and a group of 20 subjects who used a placebo formulation that contained no γ-amino-β-hydroxybutyric acid. After continuous use for eight weeks, the minimum electrical current perceived as irritation (current perception threshold or CPT) was significantly higher in the prototype formulation group than in the placebo formulation group (Figure 5). Also, a survey conducted after completion of the continuous use study revealed that the proportion of subjects who perceived a decrease in their discomfort such as tingling and burning sensations in daily life was significantly higher in the prototype formulation group than in the placebo formulation group (Figure 6).

Summary

Kao has revealed that in sensitive skin, the distribution of nerve fibers within the epidermis is altered, and one reason for the sensitivity to irritation could be the extension of nerve fibers deep into the stratum corneum. Decreased claudin-3 expression is thought to contribute to the changes in the barrier function of epidermal tight junctions.

Also, Kao searched for cosmetic materials that enhance the function of tight junctions and showed that continuous use of a formulation containing γ-amino-β-hydroxybutyric acid decreased characteristic tingling and burning sensations in sensitive skin. Kao will continue its research into the structure and function of the skin to advance the fundamental understanding of sensitive skin, with the aim of developing skin care technologies that will improve consumers’ quality of life.

References:

1. “Sensitive skin with a tendency of decreased skin barrier function has a similar ceramide profile to skin with atopic dermatitis,” February 28, 2023 Kao news release (in Japanese).

2. Sensitive skin group: lactic acid irritation score (which indicates sensitivity to irritants) of 1.5 or higher (N=3), Healthy skin group: no awareness of sensitive skin, score of 0 (N=3).

3. Those with a 250 Hz current perception threshold (CPT) of 10 or less, using a Neurometer (particularly sensitive to tingling and burning sensations.