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ABSTRACT: An erythematous and hypersensitive vestibular mucosa has been observed during the use of combined oral contraceptives (COC). Hormonal effects on the vestibular morphology have not been studied.
Our aim was to evaluate the morphology of the vulval vestibular mucosa during the influence of COC and during the menstrual cycle.
Forty-five healthy women (20 using COC and 25 not using COC) were included. A 6-mm punch biopsy was obtained from the right posterior vestibule on days 7-11 of the menstrual cycle. A corresponding biopsy was taken 2 weeks later in 16 women without COC. The epithelial morphology was estimated by measuring interdermal papilla distance, dermal papilla to surface, from basal layer to surface and width of dermal papillae. A histopathological assessment was made.
The vulval vestibular mucosa of women using COC displayed a larger distance between the dermal papillae (P = 0.04) and a larger space from the dermal papillae to the epithelial surface (P = 0.03) compared with controls in the follicular phase. Women without COC displayed a larger interdermal papilla distance in the luteal phase compared with the follicular phase, P = 0.02. Histopathology showed more superficial blood vessels in the COC users (P < 0.01).
The vulval vestibular mucosa of women with COC display an altered morphological pattern with shallow and sparse dermal papillae compared with the follicular phase. Similar findings are seen in women without COC during the luteal phase which indicate a gestagenic effect on the mucosa. Associations between the morphological pattern and changes in mucosal mechanical sensitivity require further studies.
British Journal of Dermatology 10/2007; 157(3):487-93. · 3.67 Impact Factor
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ABSTRACT: To evaluate vascular changes as a possible underlying cause of mucosal erythema in women with vulvar vestibulitis.
Laser Doppler perfusion imaging was used to map the superficial blood flow in the vestibular mucosa in 20 women with vestibulitis and in 21 healthy control subjects. A possible correlation between perfusion values and graded erythema (1-5) around the vaginal introitus was analyzed. Changes in microvascular density in the posterior part of the mucosa were investigated in sections from ten patients and ten controls by a computer-assisted image-processing program. Induced vasoconstriction of terminal arterioles in the same posterior area was also studied.
Significant increases in perfusion values were registered in the posterior parts of the vestibular mucosa in patients compared with controls. The highest blood flow was registered in the posterior fourchette. The most pronounced erythema was also located in the posterior vestibule in the patients. However, there was no significant correlation between perfusion values and degree of erythema in the same individual. The microvascular density or the ability of vestibular arterioles to constrict did not differ between patients and controls.
Women with vestibulitis have an increased superficial blood flow and erythema in the posterior parts of the vestibular mucosa. The increased perfusion, most probably caused by a neurogenic vasodilatation contributes to, but does not fully explain the erythema. Atrophic changes of the surface epithelium should also be considered in the evaluation of an erythema.
Obstetrics and Gynecology 01/2002; 98(6):1067-74. · 4.73 Impact Factor
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ABSTRACT: Vulvar vestibulitis syndrome (VVS) is a long lasting disorder of superficial dyspareunia in young women. Quantitative sensory testing, including mechanical and temperature pain thresholds and warm/cold difference limen (WCL), was performed in the vestibular mucosa in 22 women (mean age 25.0 years) with vestibulitis and 20 control subjects (mean age 25.6 years). The tests were carried out on days 7-11 of the menstrual cycle. Patients had allodynia to mechanical testing with von Frey filaments, 14.3+/-3.1mN in the symptomatic posterior area as compared with 158+/-33.5mN in healthy subjects, P<0.0001. The pain threshold to heat was 38.6+/-0.6 degrees C in patients and 43.8+/-0.8 degrees C in controls, P<0.0001. In addition, pain threshold to cold was 21.6+/-1.2 degrees C in patients whereas cooling down to 6 degrees C was usually not painful in controls. WCL was 4.9+/-0.5 degrees C in patients and 9.6+/-1.5 degrees C in healthy subjects, P<0.01. The results are compatible with the hypothesis that patients with VVS have an increased innervation and/or sensitization of thermoreceptors and nociceptors in their vestibular mucosa.
Pain 11/2001; 94(2):177-83. · 5.78 Impact Factor
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ABSTRACT: Although women with vulvar vestibulitis syndrome have principal symptoms of inflammation such as local erythema and pain in the mucosa around the vaginal introitus, it is not clear if vestibulitis is an inflammatory condition. Cyclooxygenase 2 and inducible nitric oxide synthase are known to be upregulated during inflammation. The aim of the present study was to analyze the expression of these enzymes in the vestibular mucosa in order to evaluate the inflammatory activity in the tissue.
Ten women fulfilling Friedrich's criteria of vulvar vestibulitis syndrome and ten control subjects were included in the study. Punch biopsies were obtained from the vestibular mucosa for analysis of cyclooxygenas 2 and inducible nitric oxide synthase, using indirect immunohistochemistry and Western dot-blot analyses.
Both methods used showed low expression of cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of all women. There was no difference observed between the groups.
There is a low expression of the inflammatory markers cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of women with vulvar vestibulitis syndrome as well as in healthy control subjects. The results indicate no active inflammation present and imply that topical corticosteroids in the treatment of vulvar vestibulitis are unfounded.
Acta Obstetricia Et Gynecologica Scandinavica 08/2001; 80(7):638-44. · 1.77 Impact Factor
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ABSTRACT: No morphologically defined synaptic structures have so far been detected between nerve terminals and the dentine-producing odontoblasts. Recent studies of the molecular mechanisms in neuronal exocytosis have identified several proteins that participate in synaptic-vesicle exocytosis. By localizing these proteins with immunohistochemical methods, information about the capacity for synaptic exocytosis should be obtained. Here, antibodies directed against some of the exocytosis-related proteins were used to investigate whether they are present in nerve fibers within the dentinal tubules in rat molars. Antibodies against synaptosome-associated protein of 25 kDa, Rab 3, synaptotagmin and synapsin all produced a punctuate staining pattern, suggesting that the proteins are accumulated in bouton-like elements. The results demonstrate that a set of exocytosis-related proteins is accumulated in the dentinal tubules, most probably within the intradentinal nerves. This finding is consistent with the hypothesis that intradentinal nerves can mediate efferent signals.
Archives of Oral Biology 04/1999; 44(3):223-31. · 1.60 Impact Factor
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ABSTRACT: Women with vulvar vestibulitis syndrome (VVS) have a distinct burning pain provoked by almost any stimuli in the area around the vaginal introitus. In a previous study we observed an increased number of intraepithelial free nerve endings in women with VVS. The aim of the present study was to neurochemically characterize the superficial nerves in the vulvar vestibular mucosa of women with VVS. Immunohistochemical methods were used to detect neuropeptides normally found in various types of nerve fibers. Calcitonin gene-related peptide, which is known to exist in nociceptive afferent nerves, was the only neuropeptide detected in the superficial nerves of the vestibular mucosa. These findings confirm our previous theory that the free nerve endings within the epithelium are nociceptors.
Gynecologic and Obstetric Investigation 02/1999; 48(4):270-5. · 1.28 Impact Factor
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ABSTRACT: The intraepidermal nerves of normal adult human skin were demonstrated by employing a powerful marker of neuronal elements, protein gene product (PGP) 9.5. There were two types of epidermal nerves, free nerve endings and nerves in the Merkel cell-neurite complex. The free nerve endings distributed to, and terminated in, all the strata basale, spinosum and granulosum, and they appeared as thin fibers, mostly varicose, branched or single processed, straight or bent. They existed at every site of the human body, including face, trunk and extremities. However, the densities of these nerves varied in different body parts and areas. The number of nerves decreased from the trunk to the distal parts of the limbs, and small denser 'innervation patches' showed up in the epidermis which were identified in confocal microscopy as one morphologic terminal field coming from the same dermal nerve bundle. This study has confirmed the existence of epidermal nerves in normal adult human skin, and presented a more clear picture than earlier. The difference between densities of epidermal nerves at different body areas implies area-specific functions of the intraepidermal nerve terminals. The observed intraepithelial nerve fibers may have a pain-perceiving role, however, also trophic or immunoregulatory roles can not be excluded.
Journal of the Peripheral Nervous System 02/1999; 4(1):43-52. · 2.80 Impact Factor
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ABSTRACT: The proper assessment of neuron numbers in the nervous system during physiological and pathological conditions, as well as following various treatments, has always been an important part of neuroscience. The present paper evaluates three methods for numerical estimates of nerves in epithelium: I) unbiased nerve fiber profile and nerve fiber fragment estimation methods, II) the traditional method of counting whole nerve fibers, and III) the nerve fiber estimation method. In addition, an unbiased nerve length estimation method was evaluated. Of these four methods, the nerve length per volume method was theoretically optimal, but more time-consuming than the others. The numbers obtained with the methods of nerve fiber profile, nerve fragment and nerve fiber estimation are dependent on the thickness of the epithelium and the sections as well as certain shape factors of the counted fiber. However for those, the actual counting can readily be performed in the microscope and is consequently quick and relatively inexpensive. The statistical analysis showed a very good correlation (R > 0.96) between the three numerical methods, meaning that basically any method could be used. However, dependent on theoretical and practical considerations and the correlation statistics, it may be concluded that the nerve fiber profile or fragment estimation methods should be employed if differences in epithelial and section thickness and the nerve fibers shape factors can be controlled. Such drawbacks are not inherent in the nerve length estimation method and, thus, it can generally be applied.
Journal of the Peripheral Nervous System 02/1999; 4(1):53-7. · 2.80 Impact Factor
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ABSTRACT: Women with vulvar vestibulitis syndrome (VVS) suffer from severe pain and discomfort in the area around the introitus at almost any stimulus that causes pressure within the vestibule. In spite of the severe sensory symptoms present in these women, the influence of the peripheral nerves in the vulvar vestibulum has not been clarified before. In this study the nerve supply in the vestibular mucosa in women with VVS and in healthy women free from vulvar symptoms has been revealed by PGP 9.5 immunohistochemistry. The results show a significant increase in the number of intraepithelial nerve endings in women with VVS, indicating an alteration in the nerve supply in the afflicted area.
Gynecologic and Obstetric Investigation 02/1998; 46(4):256-60. · 1.28 Impact Factor
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ABSTRACT: To determine whether there is a difference in the innervation of the paraurethral vaginal epithelium between stress urinary incontinent women of fertile age and comparable controls.
Transvaginal biopsies close to the external orifice of the urethra were obtained from 11 stress urinary incontinent women and from ten comparable controls. The specimens were processed for indirect immunohistochemistry using protein gene product 9.5 (PGP 9.5) as a general neuronal marker. From each biopsy, ten randomly selected fields of 1 mm2 projected area were investigated and nerve fibre profiles were quantificated in a microscope equipped with light- and dark-field optics.
Nerve fibre profiles/mm2 of projected epithelial area were significantly lower in the incontinent group than in the control group (P < 0.01).
Our study indicates that stress urinary incontinent women have a significantly lower total innervation of the paraurethral vaginal epithelium than continent controls.
European Journal of Obstetrics & Gynecology and Reproductive Biology 04/1997; 72(2):195-8. · 1.97 Impact Factor
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ABSTRACT: In the present study, facial skin from so-called "screen dermatitis" patients were compared with corresponding material from normal healthy volunteers. The aim of the study was to evaluate possible markers to be used for future double-blind or blind provocation investigations. Differences were found for the biological markers calcitonin gene-related peptide (CGRP), somatostatin (SOM), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), neuropeptide tyrosine (NPY), protein S-100 (S-100), neuron-specific enolase (NSE), protein gene product (PGP) 9.5 and phenylethanolamine N-methyltransferase (PNMT). The overall impression in the blind-coded material was such that it turned out easy to blindly separate the two groups from each other. However, no single marker was 100% able to pin-point the difference, although some were quite powerful in doing so (CGRP, SOM, S-100). However, it has to be pointed out that we cannot, based upon the present results, draw any definitive conclusions about the cause of the changes observed. Whether this is due to electric or magnetic fields, a surrounding airborne chemical, humidity, heating, stress factors, or something else, still remains an open question. Blind or double-blind provocations in a controlled environment are necessary to elucidate possible underlying causes for the changes reported in this investigation.
Experimental Dermatology 11/1996; 5(5):279-85. · 3.54 Impact Factor
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ABSTRACT: The purpose of the present investigation was to study resorption and regeneration of periodontal tissues incident to orthodontic tooth movement, in particular cells resorbing the root surface and the subsequent regeneration of the periodontal epithelial network and forming reparative cementum. The study was carried out using a select number of immunohistochemical markers on extracted human teeth which had been treated orthodontically. The most striking finding in the resorbing areas was the presence of what appeared to be two populations of KP 1+ mononuclear cells located at a distance of 50-100 microns from the root surface and multinucleated cells in resorption lacunae in close contact with the root surface. KP 1+ has previously not been reported for odontoclasts. The mononuclear KP 1+ cells in the periodontal ligament may represent either precursors to odontoclasts or phagocytic scavenger cells of the macrophage lineage. The subsequent healing of the resorption lacunae was characterized by re-establishment of nervous, vascular and epithelial tissues as evidenced by S-100+ filamentous delicate structures, factor VIII+ vessels and cytokeratin+ clusters of cells, respectively. However, cytokeratin+ single cells in close contact with the unresorbed cementum did not re-appear within the healing period. Although the present results are not quantitative in nature, cementoblasts located in the vicinity of resorption lacunae, especially healing ones, appeared to show an up-regulation of epidermal growth factor (EGF) receptors. It may be suggested the intense positive staining for EGF receptors may be an expression of an auto- or paracrine stimulatory pathway increasing the rate of reparative cementum formation.
The European Journal of Orthodontics 11/1996; 18(5):435-44. · 0.89 Impact Factor
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ABSTRACT: Current conflicting information on the innervation of the human oral cavity indicates technical problems such as different detectability of the neural structures according to the various staining methods used and difficulties in reproducibility. The possibility of intraoral regional differences has not been properly considered.
Human biopsies of mucosa from different intraoral regions were prepared for immunohistochemistry using protein gene product 9.5 (PGP 9.5; a marker for neuronal structures).
Nerves were found consistently in all the biopsies. The neural pattern showed clear regional differences. Intraepithelial nerve fibers were found in the gingiva, labia, palate, within certain fungiform papillae, and in some salivary excretory ducts. Organized nerve endings were found in varying frequencies in all but one (sublingual) region, appearing as lamellar (Meissner-like), coiled or glomerular neural structures. Merkel cell-neurite complexes were observed in the buccal, gingival, and palatal epithelia. Immunoreactive cells with many similarities to Merkel cells but without a neural connection were also encountered.
Conflicting results from earlier innervation studies of the oral cavity could be attributed to regional innervation differences. The distribution of the nerves also casts doubt on some of the present theories concerning the function(s) of intraoral nerves, such as the free nerve endings and the Merkel cell-neurite complexes.
The Anatomical Record 09/1996; 245(4):621-32.
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ABSTRACT: Soft tissues surrounding Brånemark titanium implants and single crystal sapphire implants were studied by conventional light- and transmission electron microscopy and by immunohistochemical markers for cytokeratin, protein S-100, Factor VIII and KP1. Histological sections of biopsies obtained from clinically healthy peri-implant mucosa were separated into a keratinized outer implant epithelium and an inner, non-keratinized epithelium, both immunoreactive towards cytokeratin. The inner implant epithelium terminated in a junctional epithelium, apically not a few cell layers thick. The cells adjacent to the implant showed a condensed cytoplasm, resembling hemidesmosomes. In the underlying connective tissue, rich in fibroblasts and factor VIII immunoreactive blood vessels, the bundles of collagen ran in different directions. S-100 immunoreactive nerve structures were more frequently found beneath the outer than the inner implant epithelium. Inflammatory cell infiltrates, some KP1 positive, were observed in the apical parts of the inner implant epithelium. S-100 positive Langerhans' cells were present mainly within the the outer implant epithelium. For the two implant systems, the techniques disclosed no qualitative structural differences in the adjacent soft tissues.
Clinical Oral Implants Research 04/1996; 7(1):1-10. · 2.51 Impact Factor
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ABSTRACT: An intradermal administration of histamine into human skin results in a local erythema, edema and often also the sensations of itch and/or pain. These effects have classically been attributed to the presence of histamine-containing mast cells. However, in the present investigation, we report the observation of histamine-immunoreactive nerves in the skin of Sprague-Dawley rats using a new and highly sensitive immunohistochemical approach. These data suggest a more direct route of cutaneous histamine effects, mediated exclusively by the peripheral nervous system. The findings could also give a new basis for explaining histamine-related issues, such as itch.
Experimental Dermatology 05/1995; 4(2):93-6. · 3.54 Impact Factor
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ABSTRACT: Dendritic cells marked by protein S-100 (S-100) antiserum in the suprabasal layers of the epidermis have previously been identified to be Langerhans' cells. In this study, S-100 immunoreactive cells have been investigated in psoriatic lesioned skin during and after peptide T treatment. Peptide T is an octapeptide with affinity for the CD4 receptor. Nine patients were intravenously infused with peptide T, 2 mg in 500 ml saline per day for 28 days. Sections from involved skin before, every week during, and after the treatment were processed by indirect immunofluorescence using S-100 antiserum. Before the treatment the epidermal Langerhans' cells were numerically decreased or even completely gone in the involved skin of psoriasis as compared to skin from normal healthy controls, while the dermal dendritic cells instead were increased and gathered in cell clusters around vascular structures. Four of the nine patients had histopathological improvements after the peptide T treatment, and, in those cases, the dendritic cells in the dermis were reduced in number, and the Langerhans' cells in the epidermis were numerically increased as well as even reversed to normal position and morphology. These changes in the distribution and density of Langerhans' cells represent their rearrangement during the course of psoriasis and/or the remission after peptide T treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Dermatological Science 02/1995; 9(1):20-6. · 3.72 Impact Factor
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ABSTRACT: In order to obtain a description of the innervation of the vaginal wall we employed an antiserum against the general neuronal marker, protein gene product 9.5, on normal human vaginal mucosa. Specimens were taken from the anterior and posterior fornices, from the anterior vaginal wall at the bladder neck level and from the introitus vaginae region, and then processed for indirect immunohistochemistry. All regions studied revealed a profound innervation, although regional differences were noted. The more distal areas of the vaginal wall had more nerve fibers compared to the more proximal parts. Also, biopsies from the anterior wall generally were more densely innervated than the posterior wall. Some large nerve coils were observed in lamina propria of the anterior wall as well as gatherings of thick-walled medium-sized blood vessels. Free intraepithelial nerve endings were only detected in the introitus vaginae region. These fibers were very thin, always varicose and could be observed just a few cell layers from the surface. In this part of the vagina, protein gene product 9.5 antibodies also stained cells within the basal parts of the epithelium. These cells were also neurone-specific enolase positive and resembled, from a morphological point of view, Merkel cells.
Acta Anatomica 02/1995; 153(2):119-26.
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ABSTRACT: To prove the existence of human intraepidermal nerve fibers at the electron microscopic level, we used both conventional and immunohistochemical ultrastructural techniques. Specimens were obtained from skin of the back, one of the most densely innervated areas of the human epidermis. The immunohistochemical marker protein gene product 9.5 was chosen because it is highly potent in labeling nerves. Thin nerve fibers were found in the basal, spinous, and granular layers of the epidermis with both techniques used, although it was more difficult to identify the nervous structures with the conventional method. The nerves appeared in the intercellular spaces and contacted keratinocyte cell bodies or cilia by membrane-membrane apposition, but without any specialized structures. Nerve fibers in the very superficial part of the vital human epidermis have not been described before at the ultrastructural level.
Journal of Investigative Dermatology 02/1995; 104(1):134-7. · 6.31 Impact Factor
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British Journal of Dermatology 12/1994; 131(5):742-3. · 3.67 Impact Factor
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ABSTRACT: An open-field provocation, in front of an ordinary TV set, of 2 patients regarding themselves as suffering from skin problems due to work at video display terminals (VDTs) is presented. Using immunohistochemistry, in combination with a wide range of antisera directed towards cellular and neurochemical markers, we were able to show a high-to-very high number of somatostatin-immunoreactive dendritic cells as well as histamine-positive mast cells in skin biopsies from the anterior neck taken before the start of the provocation. At the end of the provocation the number of mast cells was unchanged; however, the somatostatin-positive cells had seemingly disappeared. The reason for this latter findings is discussed in terms of loss of immunoreactivity, increase of breakdown, etc. The high number of mast cells present may explain the clinical symptoms of itch, pain, edema and erythema. Naturally, in view of the present public debate, the observed results are highly provocative and, we believe, have to be taken seriously.
Experimental Dermatology 11/1994; 3(5):234-8. · 3.54 Impact Factor
