Working with Professor Kenji Kabashima at Kyoto University’s Graduate School of Medicine, researchers at Kao’s Skin Care Research Laboratory have shown that sensitive skin has nerve fibres extending unusually deep into the stratum corneum (outermost layer of the skin).

The company believes this nerve overextension happens due to weakened “tight junctions”, or microscopic seals between skin cells that form part of the skin’s barrier.

Kao also identified a small molecule that appeared to strengthen these junctions and relieve the discomfort commonly experienced by people with sensitive skin.

The findings were presented at the 50th Convention of the Japanese Cosmetic Science Society in Tokyo in July, where the work received the Convention President’s Award.

Kao said the discovery could help develop new skin care technologies that would improve quality of life for people who suffer from irritation and hypersensitivity.

Hidden triggers

Sensitive skin is a common yet poorly understood condition. It refers to skin that reacts with pain, itching, tingling, or burning to everyday stimuli such as cosmetics, temperature changes, or friction that would not normally cause discomfort.

While experts have long recognised that a weak barrier in the stratum corneum can make the skin more vulnerable, the neural basis of sensitive skin has remained unclear.

Kao, which has researched irritation-prone skin for decades, decided to look deeper not only at the skin’s lipids, such as ceramides, but also at the position and behaviour of nerve fibres within the skin layers.

Deeper nerve fibres in sensitive skin

The researchers examined the skin of six Japanese women aged between 20 and 50. Three participants reported sensitive skin and scored 1.5 or higher on a lactic acid irritation test, while the other three had no sensitivity and scored zero.

Microscopic imaging revealed a clear difference between the two groups. In sensitive skin, nerve fibres were more numerous in the stratum corneum, crossing the boundary formed by tight junctions.

These junctions, found in the granular layer of the epidermis, normally hold neighbouring cells tightly together, preventing foreign substances from entering and water from escaping. They also serve as a fence that keeps nerve endings confined to deeper layers.

When this structure weakens, the Kao team explained, nerve fibres can extend beyond their usual limits — closer to the skin surface, where they are easily activated by mild stimuli. The researchers said this may explain why people with sensitive skin often experience pain or tingling even when there is no visible sign of irritation.

Tight junction research

To understand why the junctions were weaker, the researchers studied gene expression in the skin samples. They discovered that claudin-3, a key structural protein in tight junctions, was expressed at significantly lower levels in sensitive skin than in normal skin.

Further laboratory work confirmed the protein’s importance. When claudin-3 activity was reduced in cultured human skin cells, barrier strength dropped, as shown by lower transepithelial electrical resistance (TEER) values — a standard measure of how well the skin prevents electrical current, and by extension, irritants, from passing through.

These results suggested that reduced claudin-3 expression weakened the tight junctions, and as a result, nerve fibres could extend deeper into the outer layer of the skin, making it more sensitive to external stimuli.

Based on this insight, Kao screened various cosmetic ingredients to find those that could boost claudin-3 and strengthen the tight junction barrier. The standout candidate was γ-amino-β-hydroxybutyric acid, an amino acid derivative.

When tested in laboratory-grown human skin cells, this ingredient significantly increased claudin-3 levels in a dose-dependent manner. It also raised TEER values, suggesting tighter and more effective junctions.

Encouraged by these results, Kao incorporated the molecule into a prototype skin care formulation and designed a human trial to test its effect on sensitive skin sensations.

Eight-week trial shows promising results

The company recruited 40 women aged 20 to 40 who reported having sensitive skin and scored high on irritation sensitivity tests. Using a neurometer, researchers measured each participant’s current perception threshold (CPT), an electrical test used to assess how easily nerve endings are activated.

Participants with low CPT values (meaning higher sensitivity) were randomly assigned to one of two groups. One group used the γ-amino-β-hydroxybutyric acid formula for eight weeks, while the other used a placebo cream with the same base but no active ingredient.

At the end of the study, the group using the active formula showed a significant increase in CPT, indicating that their nerves had become less reactive.

In addition, surveys showed that more participants in the active group reported a noticeable reduction in tingling and burning sensations than in the placebo group.

Kao interpreted these findings as evidence that strengthening tight junctions could “fence off” nerve fibres, reducing hypersensitivity and discomfort in daily life.

A new path for skin care innovation

Kao sees these findings as a scientific and technological breakthrough, as the study provided a molecular explanation for the stinging and burning, which consumers with sensitive skin often describe as sensations that can affect confidence and quality of life.

By identifying γ-amino-β-hydroxybutyric acid as a compound that supports tight junction integrity, the company has created a bridge between basic biological research and potential product applications.

Kao has a long history in skin barrier science, including work on ceramides, which form the lipid matrix between cells. This latest research extends that expertise to the level of tight junctions in the granular layer, and explores how changes at this level can directly influence nerve sensitivity.

The company stated that it would continue exploring the relationship between skin structure, nerve function, and sensory response, with plans to apply these insights to the development of skin care technologies that strengthen the skin barrier, reduce irritation, and enhance overall comfort for people with sensitive skin.