Studies on nerve terminations in human mucosa and skin

In spite of their accessibility and important sensory function, the nervous tissue components of human oral and vaginal mucosa and skin have been subject to very few, if any, systematic investigations. Studies on the innervation of oral tissues have mainly focused on the dental pulp, the periodontium and the gingiva, probably because of specific clinical interest, thus largely neglecting the mucosa. Genital studies comprise only in a few cases the vagina and when the vagina is included, morphological descriptions of the innervation are often very meager. In cutaneous innervation, interest has been focused on certain neural end structures, e.g. Meissner corpuscles, Merkel cell-neurite complexes, hair follicles and Pacinian corpuscles. The general purpose of the present thesis was to further our understanding of the neurohistology of the human mucosa and skin. Particular emphasis was put on regional differences in innervation within and between organs. The work also includes studies on quantification methods suitable for unbiased estimates of peripheral innervation. The last part of the thesis deals with nerve-related pathosis, where the knowledge from the first parts is applied.

The following specific conclusions were drawn: (1) The human oral mucosa possess intraepithelial nerve fibres, Merkel cell-neurite complexes, non-innervated Merkelcell-like cells, lamellar and glomerular nerve corpuscles, nerves in close connection to blood vessels, accessory salivary glands, salivary gland ducts and different sized nerve bundles. Salient differences exist both in number and organisation of the intraepithelial nerve endings as well as organised corpuscles; (2) The human vaginal mucosa possess intraepithelial nerve fibres, non-innervated Merkel cell-like cells, glomerular nerve corpuscles, nerves in close connection to blood vessels and smooth muscle cells and different sized nerve bundles. The distal areas of the vaginal wall have more nerve fibres compared to the more proximal parts. The anterior wall is generally more densely innervated than the posterior wall. Larger nerve coils is found in the anterior vaginal wall only and intraepithelial nerves exclusively in the introitus region. (3) The human skin possess intraepithelial nerve fibres, Merkel cell-neurite complexes, lamellar nerve corpuscles, nerves in close connection to blood vessels, eccrine and apocrine sweat glands, hair follicles and the smooth muscle cells of the arrector pili as well as different sized nerve bundles. Evidence for the existence of free nerve endings in human epidermis was obtained. (4) Ultrastructural studies confirm that the PGP9.5 positive fibres throughout the whole living epidermis are nerve fibres. (5) For both theoretical and practical purposes, it was concluded that the nerve fibre profile and fragment estimation methods are simple, quick and reliable. The use of the nerve fibre estimation method is dubious and the nerve length estimation method should be used if differences in epithelial and section thickness and the nerve fibres shape factors cannot be controlled for. (6) The skin intraepithelial nerve fibres varying their number and distribution pattern between body areas, with most fibres in the back and chest skin and least in the extremities. (7) The appearance of recurrent oral herpes lesions at exclusive sites correspond with local neurohistology. Only regions with epithelial innervation will express the classical intraepithelial vesicles. (8) Stress urinary incontinent women have a significant decrease in their paraurethral innervation compared to continent controls. It is suggested that an impaired innervation may reduce the sensory feed-back in this area and result in a decreased stimulus to pelvic floor contraction in order to avoid urinary leakage.