Topical application of emollients prevents dry skin-inducible intraepidermal nerve growth in acetone-treated mice

Abstract

In common dermatoses, such as atopic dermatitis (AD), a decline in skin barrier function often accompanies an increased severity of clinical symptomatology, including pruritus [ [1] Yosipovitch G. Dry skin and impairment of barrier function associated with itch—new insights. Int J Cosmet Sci. 2004; 26: 1-7 Crossref PubMed Scopus (69) Google Scholar ]. Skin barrier disruption alters epidermal innervation and increases nerve density in the skin [ [2] Ikoma A. Steinhoff M. Stander S. Yosipovitch G. Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006; 7: 535-547 Crossref PubMed Scopus (714) Google Scholar ]. These findings are indicative of increases in sensory receptors responsive to exogenous trigger factors, suggesting that hyperinnervation is partly responsible for intense itch sensations [ [2] Ikoma A. Steinhoff M. Stander S. Yosipovitch G. Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006; 7: 535-547 Crossref PubMed Scopus (714) Google Scholar ]. Therefore, the abnormal innervation associated with skin barrier dysfunction such as dry skin has been considered as a target of antipruritic therapy. Moreover, recent studies have demonstrated that epidermal innervation is probably regulated by a fine balance of nerve elongation factors (e.g., nerve growth factor (NGF), amphiregulin, gelatinase) [ [2] Ikoma A. Steinhoff M. Stander S. Yosipovitch G. Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006; 7: 535-547 Crossref PubMed Scopus (714) Google Scholar ] and nerve repulsion factors (e.g., semaphorin 3A (Sema3A), anosmin-1) [ 2 Ikoma A. Steinhoff M. Stander S. Yosipovitch G. Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006; 7: 535-547 Crossref PubMed Scopus (714) Google Scholar , 3 Tengara S. Tominaga M. Kamo A. Taneda K. Negi O. Ogawa H. et al. Keratinocyte-derived anosmin-1, an extracellular glycoprotein encoded by X-linked Kallmann syndrome gene, is involved in modulation of epidermal nerve density in atopic dermatitis. J Dermatol Sci. 2010; 58: 64-71 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ]. Although many people use emollients daily to alleviate symptoms of clinically and subjectively dry skin [ [4] Jemec GB Moisturizers as a medical, biological, psychological, cultural, and economic factor. in: Loden M. Maibach H. Dry skin and moisturizers: chemistry and function. 2nd ed. CRC Press, FL2006: 149-154 Google Scholar ], the effects of emollients on nerve fiber density and nerve growth activity in dry skin remain unclear. We therefore examined the anti-nerve growth effects of petrolatum and heparinoid cream in the epidermis of acetone-treated mice, an animal model of acute dry skin [ [5] Tominaga M. Ozawa S. Tengara S. Ogawa H. Takamori K. Intraepidermal nerve fibers increase in dry skin of acetone-treated mice. J Dermatol Sci. 2007; 48: 103-111 Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar ].