Topical Application of Tenshino-SoftgelTM Reduces Epidermal Nerve Fiber Density in a Chronic Dry Skin Model Mouse


Background: Dry skin induces antihistamine-resistant itch, as well as epidermal hyperinnervation, which is partly responsible for peripheral itch sensitization. In acute dry skin, topical application of emollients prevents the penetration of nerve fibers into the epidermis. However, the effects of emollients on itch and epidermal hyperinnervation in individuals with chronic dry skin are poorly understood. Objective: This study examined the effects of Tenshino-softgelTM (TSG) on itch-related behavior, epidermal hyperinnervation and skin barrier function in a chronic dry skin model mouse. Methods: Chronic dry skin was induced by application of acetone/ether (1:1) mixture and water (AEW) to the rostral parts of the back of hairless mice twice daily for six consecutive days. As treatment, TSG or, as control, Vaseline (V) was applied to the same areas twice daily. Skin barrier function was evaluated by measuring transepidermal water loss (TEWL) before each treatment. Scratching behavior was recorded and analyzed using a SCLABA®-real system, and skin samples were collected for immunohistochemical assays. Results: TEWL tended to be lower and scratching bouts fewer in AEW + TSG- than in AEW-treated mice. The numbers of protein gene product 9.5-immunoreactive fibers and substance P-immunoreactive fibers were each significantly lower in the epidermis of AEW + TSG- than of AEW-treated mice, but the expression of nerve growth factor in epidermis was similar in the three groups. Semaphorin 3A expression was significantly higher in the epidermis of AEW + TSG- than of AEW- and AEW + V-treated mice. Conclusion: Topical application of TSG may attenuate itch induced by chronic dry skin through a mechanism involving the inhibition of epidermal hyperinnervation.

Share and Cite:

Noguchi, A. , Tominaga, M. , Ko, K. , Matsuda, H. , Suga, Y. , Ogawa, H. and Takamori, K. (2015) Topical Application of Tenshino-SoftgelTM Reduces Epidermal Nerve Fiber Density in a Chronic Dry Skin Model Mouse. Journal of Cosmetics, Dermatological Sciences and Applications, 5, 254-261. doi: 10.4236/jcdsa.2015.54031.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Di Nardo, A., Wertz, P., Giannetti, A. and Seidenari, S. (1998) Ceramide and Cholesterol Composition of the Skin of Patients with Atopic Dermatitis. Acta Dermato Venereologica, 78, 27-30.
[2] Thaipisuttikul, Y. (1998) Pruritic Skin Diseases in the Elderly. The Journal of Dermatology, 25, 153-157.
[3] Long, C.C. and Marks, R. (1992) Stratum Corneum Changes in Patients with Senile Pruritus. Journal of the American Academy of Dermatology, 27, 560-564.
[4] Morton, C.A., Lafferty, M., Hau, C., Henderson, I., Jones, M. and Lowe, J.G. (1996) Pruritus and Skin Hydration during Dialysis. Nephrology Dialysis Transplantation, 11, 2031-2036.
[5] Tominaga, M., Ozawa, S., Tengara, S., Ogawa, H. and Takamori, K. (2007) Intraepidermal Nerve Fibers Increase in Dry Skin of Acetone-Treated Mice. Journal of Dermatological Science, 48, 103-111.
[6] Tominaga, M., Tengara, S., Kamo, A., Ogawa, H. and Takamori, K. (2009) Psoralen-Ultraviolet A Therapy Alters Epidermal Sema3A and NGF Levels and Modulates Epidermal Innervation in Atopic Dermatitis. Journal of Dermatological Science, 55, 40-46.
[7] Tominaga, M. and Takamori, K. (2014) Itch and Nerve Fibers with Special Reference to Atopic Dermatitis: Therapeutic Implications. The Journal of Dermatology, 41, 205-212.
[8] Enoki, T., Okuda, S., Kudo, Y., Takashima, F., Sagawa, H. and Kato, I. (2010) Oligosaccharides from Agar Inhibit Pro-inflammatory Mediator Release by Inducing Heme Oxygenase 1. Bioscience, Biotechnology, and Biochemistry, 74, 766-770.
[9] Miyamoto, T., Nojima, H., Shinkado, T., Nakahashi, T. and Kuraishi, Y. (2002) Itch-Associated Response Induced by Experimental Dry Skin in Mice. The Japanese Journal of Pharmacology, 88, 285-292.
[10] Tanaka, A., Amagai, Y., Oida, K. and Matsuda, H. (2012) Recent Findings in Mouse Models for Human Atopic Dermatitis. Experimental Animals, 61, 77-84.
[11] Nie, Y., Ishii, I., Yamamoto, K., Orito, K. and Matsuda, H. (2009) Real-Time Scratching Behavior Quantification Systemfor Laboratory Mice Using High-Speed Vision. Journal of Real-Time Image Processing, 4, 181-190.
[12] Tominaga, M. and Takamori, K. (2013) An Update on Peripheral Mechanisms and Treatments of Itch. Biological and Pharmaceutical Bulletin, 36, 1241-1247.
[13] Kamo, A., Tominaga, M., Negi, O., Tengara, S., Ogawa, H. and Takamori, K. (2011) Topical Application of Emollients Prevents Dry Skin-Inducible Intraepidermal Nerve Growth in Acetone-Treated Mice. Journal of Dermatological Science, 62, 64-66.
[14] Valtcheva, M.V., Saminen, V.K., Golden, J.P., Gereau 4th, R.W. and Davidson, S. (2015) Enhanced Nonpeptidergic Intraepidermal Fiber Density and An Expanded Subset of Chloroquine-responsive Trigeminal Neurons in a Mouse Model of Dry Skin Itch. The Journal of Pain, 16, 346-356.
[15] Akiyama, T., Carstens, M.I. and Carstens, E. (2010) Enhanced Scratching Evoked by PAR-2 Agonist and 5-HT but Not Histamine in a Mouse Model of Chronic Dry Skin Itch. Pain, 151, 378-383.
[16] Yosipovitch, G. (2004) Dry Skin and Impairment of Barrier Function Associated with Itch—New Insights. International Journal of Cosmetic Science, 26, 1-7.
[17] Yamaoka, J., Di, Z.H., Sun, W. and Kawana, S. (2007) Erratum to “Changes in Cutaneous Sensory Nerve Fibers Induced by Skin-scratching in Mice”. Journal of Dermatological Science, 47, 172-182.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.