Influence of cutaneous nerves on keratinocyte proliferation and epidermal thickness in mice

We evaluated the influence of skin innervation on the epidermis in mice. Th e rich innervation of skin was demonstrated by immunocytochemistry with pro tein gene product 9.5, a ubiquitin carboxy hydrolase. Protein gene product- immunoreactive nerve fibers were in the epidermis, subepidermal plexus, der mal nerve trunks, and nerve terminals around sweat glands. Effects of dener vation on the plantar surface of the hind foot was assessed by comparing th e thickness of the epidermis, which was innervated by the sciatic nerve. Wi thin 48 h after sectioning of the sciatic nerve, protein gene product (+)-n erves in the territory of the sciatic nerve were completely degenerated. Th ere was a significant thinning of the denervated epidermis 72 h post-transe ction (30.5 +/- 1.1 vs 41.4 +/- 2.9 mu m, 74 +/- 4% of the control side). T he reduction in epidermal thickness persisted when skin remained denervated (69-75% of the control side). Incorporation of bromodeoxyuridine was reduc ed 24 h after denervation (71 +/- 6% of the control side). Reduction in bro modeoxyuridine-incorporation was most pronounced within 48 h after denervat ion (19 +/- 6% of the control side). Therefore, the reduction in bromodeoxy uridine-labeling followed a similar temporal course as the thinning of the epidermis (25-50%). Both epidermal thinning and reduced bromodeoxyuridine-l abeling were reversed by epidermal reinnervation three months after denerva tion. Patterns of keratinocyte differentiation and programmed cell death we re unaffected by skin denervation. These findings are consistent with the notion that skin innervation exerts influence on the proliferation of keratinocytes and the thickness of the ep idermis, and offers a new look at the interaction between nociceptive nerve s and their innervated targets. (C) 1999 IBRO. Published by Elsevier Scienc e Ltd.