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 beensubject to very few, if any, systematic investigations. Studies on the innervationof oral tissues have mainly focused on the dental pulp, the periodontium and thegingiva, probably because of specific clinical interest, thus largely neglectingthe mucosa. Genital studies comprise only in a few cases the vagina and when thevagina is included, morphological descriptions of the innervation are often verymeager. In cutaneous innervation, interest has been focused on certain neural endstructures, e.g. Meissner corpuscles, Merkel cell-neurite complexes, hair folliclesand Pacinian corpuscles. The general purpose of the present thesis was to further our understanding of theneurohistology of the human mucosa and skin. Particular emphasis was put on regionaldifferences in innervation within and between organs. The work also includes studieson quantification methods suitable for unbiased estimates of peripheral innervation.The last part of the thesis deals with nerve-related pathosis, where the knowledgefrom the first parts is applied. The following specific conclusions were drawn: (l)The human oral mucosa possessintraepithelial nerve fibres, Merkel cell-neurite complexes, non-innervated Merkelcell-like cells, lamellar and glomerular nerve corpuscles, nerves in close connectionto blood vessels, accessory salivary glands, salivary gland ducts and different sizednerve bundles. Salient differences exist both in number and organisation of the intraepithelialnerve endings as well as organised corpuscles; (2) The human vaginal mucosa possessintraepithelial nerve fibres, non-innervated Merkel cell-like cells, glomerular nervecorpuscles, nerves in close connection to blood vessels and smooth muscle cells anddifferent sized nerve bundles. The distal areas of the vaginal wall have more nervefibres compared to the more proximal parts. The anterior wall is generally more denselyinnervated than the posterior wall. Larger nerve coils is found in the anterior vaginalwall only and intraepithelial nerves exclusively in the introitus region. (3) Thehuman skin possess intraepithelial nerve fibres, Merkel cell-neurite complexes, lamellarnerve corpuscles, nerves in close connection to blood vessels, eccrine and apocrinesweat glands, hair follicles and the smooth muscle cells of the arrector pili aswell as different sized nerve bundles. Evidence for the existence of free nerve endingsin human epidermis was obtained. (4) Ultrastructural studies confirm that the PGP9.5 positive fibres throughout the whole living epidermis are nerve fibres. (5) Forboth theoretical and practical purpouses, it was concluded that the nerve fibre profileand fragment estimation methods are simple, quick and reliable. The use of the nervefibre estimation method is dubious and the nerve length estimation method shouldbe used if differences in epithelial and section thickness and the nerve fibres shapefactors cannot be controlled for. (6) The skin intraepithelial nerve fibres varyin their number and distribution pattern between body areas, with most fibres inthe back and chest skin and least in the extremities. (7) The appearance of recurrentoral herpes lesions at exclusive sites correspond with local neurohistology. Onlyregions with epithelial innervation will express the classical intraepithelial vesicles.(8) Stress urinary incontinent women have a significant decrease in their paraurethralinnervation compared to continent controls. It is suggested that an impaired innervationmay reduce the sensory feed-back in this area and result in a decreased stimulusto pelvic floor contraction in order to avoid urinary leakage. Keywords: Epithelium, herpes simplex, immunohistochemisry, Merkel cell, mucosa,nerves, oral, PGP 9.5, skin, stereology, urinary incontinence, vagina. ISBN 91-628-2649-