Neuropeptides in saliva of subjects with burning mouth syndrome: a pilot study

Oral Diseases (2010) 16 , 365–374 Objective: A neuropathic basis has been suggested for burning mouth syndrome (BMS) and an altered concentration of neuropeptides has been reported in lingual oral mucosa and saliva in this disease. The aims of this study were to compare the levels of nerve growth factor (NGF), substance P (SP) and degranulation products from mast cells and neutrophils in the saliva of BMS subjects with those of control subjects. Material and Methods: Salivary flow rate, protein concentration, NGF peptide and mRNA, SP, mast cells tryptase, neutrophil myeloperoxidase and calprotectin were analyzed in saliva of 20 BMS subjects and of 20 age‐ and gender‐matched healthy subjects. Results and Conclusions: NGF peptide and tryptase activity were shown to be significantly and persistently higher in saliva of BMS subjects, with respect to control values. Conversely the salivary levels of SP were shown to be significantly lower, while neutrophil markers didn’t show any change. We conclude that the neuropathic origin of the disease is confirmed at salivary level. Furthermore, the higher tryptase activity indicates a possible involvement of mast cells. The salivary neuropeptide concentration in BMS subjects, together with mast cell derived compounds, could be useful biomarkers for diagnosis and monitoring of this disease.     

Mast cell expression in oral lichen planus: A systematic review

Lichen planus is a common chronic, inflammatory, immune‐mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen planus has been debated. Establishing a definitive part played by mast cells and its degranulation would possibly provide a permanent, cost‐effective treatment modality for oral lichen planus (OLP). This review aims to study the expression of mast cells qualitatively and quantitatively in OLP. The research questions were framed to assess the mast cell count, localization within the epithelium basement membrane zone and degranulation of mast cells. We performed a systematic search of PubMed, Medline, Cochrane and Web of Science. We found a total of 120 studies from which 12 were found suitable for the review. There is a marked increase in the number of mast cells in OLP. The mast cells were seen in increased numbers in the epithelial and connective tissue junction at areas of basement membrane disruption. There was also an increase in the degranulation of mast cells. It is evident that there is an increase in the mast cell number in lichen planus and its subsequent degranulation.     

Adaptation of craniofacial muscles in subjects with craniomandibular disorders

The purpose of this study was to examine muscle function in subjects with muscle pain. Forty-three subjects with pain in the craniomandibular muscles, clinically determined by manual palpation, were studied for alteration in recruitment of temporalis, masseter, and suprahyoid muscles during a series of phasic movements. Seventeen normal subjects were used as controls. The subjects with muscle pain were divided into three subgroups: (1) those with pain in both mandibular and neck muscles; (2) those with pain in these two muscle groups with joint degeneration; and (3) those subjects with pain only in mandibular muscles. Surface electromyographic (EMG) recordings were taken as each subject performed 16 different responses in which mandibular incisor movement was tracked simultaneously. The results show that the subjects with muscle pain use their anterior temporalis muscles with less frequency (i.e., probability) and with less intensity in several responses than normal subjects. These responses include rapid vertical closing movements, retrusion, ipsilateral laterotrusion, and natural as well as contralateral mastication. The masseter muscle is impaired much less in its function, and the recruitment of the suprahyoid muscles is not affected in the patients with muscle pain. Comparison of the bilateral activity in the anterior temporalis muscles during intercuspal clenching shows that the subjects with muscle pain often demonstrate a more severe asymmetrical recruitment of these muscles than the more symmetrical recruitment seen in normal subjects. Similar observations were made for the masseter muscle. These studies demonstrate that subjects with muscle pain in craniomandibular muscles alter the recruitment of their jaw muscles, thus supporting the concept that the neuromuscular system is altered in patients with craniomandibular disorders.     

Staining mast cells in human gingiva

This study was undertaken to select a specific, consistent stain-fixative combination which permits easy identification of all mast cells in human gingiva in order that meaningful studies of alterations in mast cell populations and distributions in periodontal disease could be performed. Previous investigators have employed a variety of metachromatic or non-specific stains for such studies with highly variable and conflicting results. In this study, a number of stain-fixative combinations were investigated. The metachromatic stains (i.e. toluidine blue, methylene blue, etc.) gave inconsistent or unreliable results and were difficult to read. In the presence of inflammation mast cells were frequently indistinguishable from other cells. Other nonspecific stains (i.e. aldehyde fuchsin, Giemsa, etc.) presented similar difficulties. The use of aqueous as compared with non-aqueous fixatives had no consistent effect on numbers of mast cells which could be visualized. For reliable, specific, easily readable staining of human gingival mast cells, the histochemical technique for the demonstration of the trypsin-like esterase activity in mast cells devised by and (1962) proved to be vastly superior to all other techniques studied.     

Influence of mucosal mechanoreceptors on elevator muscle activity in healthy subjects

An analysis of saliva swallowing and tonic electromyographic activity was undertaken in 15 healthy subjects with complete natural dentitions with and without a palatal base inserted. Recordings were performed by placing surface electrodes on the left anterior temporal and masseter muscles. In eight subjects tonic electromyographic patterns of activity differed for the two muscles, depending upon the presence of the palatal base, whereas during swallowing of saliva only four subjects showed different patterns. In tonic activity of elevator muscles, there is probably a differential peripheral and/or central modulation of motoneuron pools of both elevator muscles. The lower different pattern in electromyographic activity of the two muscles during saliva swallowing in the intercuspal position suggests that periodontal mechanoreceptor stimulation might have such a powerful influence on electromyographic activity of both muscles that any difference originating in other inputs could have been obscured.     

Salivary gland changes in chronic fatigue syndrome: a case-controlled preliminary histologic study

OBJECTIVE: The purpose of this preliminary study is to compare labial salivary gland changes of 11 patients with chronic fatigue syndrome with control subjects. STUDY DESIGN: Changes in labial salivary glands were graded from 0 to 3+ for acinar dilatation, ductal dilatation, periductal fibrosis, plasmacytic infiltrate, lymphocytic infiltrate, mast cell infiltrate, and lymphocytic aggregates or foci. RESULTS: Four of the 11 subjects had 2+ to 3+ changes in at least 4 of the 7 parameters examined. Only the presence of mast cells was statistically significant between the 2 groups. Two of these 4 patients had 1 lymphocytic focus per 4 mm(2) of tissue. CONCLUSIONS: The salivary gland changes in patients with chronic fatigue syndrome show varying degrees of ductal and acinar dilatation, periductal fibrosis, lymphoplasmacytic infiltrates, and occasional lymphocytic foci, all suggestive of primary gland damage. The one parameter that showed statistical significance was the presence of mast cells (Fisher exact test, 0.0125).     

肥大细胞脱颗粒在牙周炎病理中的作用

目的:探讨肥大细胞脱颗粒在牙周炎病理中的意义。方法:将自愿接受研究的受试者分为3组:轻度慢性牙周炎组(轻度组,17例)、重度慢性牙周炎组(重度组,18例)、正常对照组(15例)。取牙龈活检组织制作连续切片,HE染色在光镜下观察各组牙周组织的组织学改变;甲苯胺蓝染色法观察各组肥大细胞的数量及肥大细胞脱颗粒状况;天狼猩红染色法观察各组牙周组织纤维化的程度。结果:与正常对照组相比,各慢性牙周炎组的牙周组织中肥大细胞显著增多(P<0.01);重度组与轻度组相比较肥大细胞数量和脱颗粒率均明显升高(P<0.01),牙周组织纤维化程度更加严重(P<0.05)。结论:肥大细胞的募集、脱颗粒和纤维化程度与牙周炎的严重程度相关,提示肥大细胞可能在牙周炎的发病和疾病进程中起着重要的作用。     

Comparative analysis of the mast cell density in normal oral mucosa, actinic cheilitis and lip squamous cell carcinoma

Previous studies have shown that the number of mast cells is increased in ultraviolet (UV) irradiated skin and in neoplasias. Actinic cheilitis (AC) is a lesion caused by excessive exposure to sunlight that can transform into lip squamous cell carcinoma. The aim of this study was to compare the number of mast cells in 4 groups: NOM = normal oral mucosa (n=6); MDAC = mild dysplasia in actinic cheilitis (n=13); SDAC = severe dysplasia in actinic cheilitis (n=13); and LSCC = lip squamous cell carcinoma (n=15). The sections were stained by histochemical technique of blue toluidine and visual counting was performed with the aid of a reticulum coupled to the microscope ocular. A calibrated observer performed the count in 5 fields by case at x400 magnification. The largest mean number of mast cells per group was observed in LSCC (40.1), followed by MDAC (30.5), SDAC (28.6) and NOM (12.2). There were significant differences between NOM and MDAC (p<0.05) and between NOM and LSCC (p<0.05). The increased density of mast cells observed in AC and in LSCC compared to NOM suggests a role for the mast cells in the development of these lesions.     

Correlations between EMG jaw muscle activity and facial morphology in complete denture wearers

In a sample of fifteen partially edentulous subjects assigned for immediate complete denture treatment, a correlation analysis was performed between pre-extraction facial morphology determined from lateral cephalograms, and EMG activity of the anterior temporal and masseter muscles in maximal clench and tapping of teeth. Marked correlations observed between vertical and sagittal jaw relations and mean voltages of the jaw-closing muscles indicated strong biting activity in subjects with a square facial type. No significant associations were observed between biting strength and the age of the subjects. Correlations between facial morphological changes and changes in EMG biting activity after denture insertion and during 1 year of denture wear indicated that the anterior temporal muscles were extremely sensitive to sagittal changes in anterior occlusion. The masseter muscles were less sensitive, but responded in some instances to changes in vertical jaw relationship.     

Facial pain in negative and positive work of human jaw muscles

abstract – Ten healthy human male subjects with a mean age of 21 years performed negative and negative/positive work with the jaw muscles for about 21 min. The average amount of negative work was 13.3 kgm, while that of negative/positive work was 48.5 kgm. Eight subjects developed either spontaneous or provoked facial pain subsequent to the exercise. No positive correlations were demonstrated between the total number of facial pain sites and the amounts of work and power of the muscles, nor between the number of pain sites and the speed of mandibular movement. It is suggested that the appearance of facial pain was associated with the pre-experimental strength and conditioning of the jaw muscles.     

Facial pain in negative and positive work of human jaw muscles.

Ten healthy human male subjects with a mean age of 21 years performed negative and negative/positive work with the jaw muscles for about 21 min. The average amount of negative work was 13.3 kgm, while that of negative/positive work was 48.5 kgm. Eight subjects developed either spontaneous or provoked facial pain subsequent to the exercise. No positive correlations were demonstrated between the total number of facial pain sites and the amounts of work and power of the muscles, nor between the number of pain sites and the speed of mandibular movement. It is suggested that the appearance of facial pain was associated with the pre-experimental strength and conditioning of the jaw muscles.     

Substance P and mast cells: preliminary histologic analysis of the human temporomandibular joint

PURPOSE: Neuropeptide-containing nerves can serve as a mechanism for nervous system regulation of host defense responses. Because bacteria associated with reactive arthritis have been identified in the temporomandibular joint (TMJ), this study investigates whether the presence of substance P (SP) neuropeptide-containing nerves and mast cells can be identified in the TMJ. MATERIAL AND METHODS: Posterior bilaminar tissue removed during TMJ surgery from 9 women was evaluated for the presence of neuropeptide-containing nerves by staining with a monoclonal antibody to SP. Staining of the TMJ tissue sections with 0.5% toluidine blue was performed to identify the presence of mast cells. RESULTS: SP-containing nerves and mast cells were identified within the posterior bilaminar tissue associated with the vasculature. CONCLUSIONS: The presence of neuropeptide nerves and mast cells within the TMJ has been shown. Mast cell degranulation products and SP release can contribute to TMJ inflammation.     

Proliferation of mast cells in normal and DMBA-treated mouse skin

To examine the pattern of proliferation of mast cells in the skin of Swiss Webster mice, single or multiple pulses of 3H-thymidine, autoradiography and selective staining techniques were combined to detect DNA synthesis. A very low labelling index was found for the mast cells of normal skin but alteration of the mast-cell population using the chemical carcinogen dimethylbenzathracene led to increased labelling of mast cells. A series of studies of experimentally altered skin showed a pattern of mast cell labelling which suggested derivation of new mast cells by local self-replication. The labelling pattern indicated that mast cells labelled after 1 h divided to produce 2 daughter cells and that the rate of increase in the number of labelled mast cells following repeated labelling for up to 20 days was linear. These data do not suggest major recruitment of mast cells from a distant source during this period.     

The immediate effect of splint-induced changes in jaw positioning on the asymmetry of submaximal masticatory muscle activity

Maxillary full-arch splints in the retruded position (RP) and in a right lateral occlusion (1.0-1.5 mm to the right of the retruded contact position) were fabricated for ten subjects. Surface electromyography of the masseter and anterior temporal muscles was performed during submaximal clenching in order to investigate the immediate effects of the splints on the activity patterns of these muscles relative to the patterns found with the subjects occlusion in the inter-cuspal position. The splints in the RP were found to have no effect on the asymmetry of the activity of the masseter and the anterior temporal muscles, while the splints in a right lateral occlusion resulted in relative increases in right anterior temporal muscle activity (P less than 0.005).     

Proliferation of mast cells in normal and DMBA-treated mouse skin

To examine the pattern of proliferation of mast cells in the skin of Swiss Webster mice, single or multiple pulses of -³H-thymidine. autoradiography and selective staining techniques were combined to detect DNA synthesis. A very low labelling index was found for the mast cells of normal skin but alteration of the mast-cell population using the chemical carcinogen dimethylbenzanthracene led to increased labelling of mast cells. A series of studies of experimentally altered skin showed a pattern of mast cell labelling which suggested derivation of new mast cells by local self-replication. The labelling pattern indicated that mast cells labelled after 1 h divided to produce 2 daughter cells and that the rate of increase in the number of labelled mast cells following repeated labelling for up to 20 days was linear. These data do not suggest major recruitment of mast cells from a distant source during this period.     

Silent Period of Masticatory Cycles in Dentate Subjects and Complete Denture Wearers

Purpose: The purpose of this study was to assess, through electromyographic activity (EMG), the silent period (SP) of masseter and anterior temporal muscles in dentate subjects (DS) and complete denture wearers (CDW). Materials and Methods: The evaluations were performed at the initial and final period of the mastication for the DS group. For the CDW group, the evaluations were performed at the initial period of mastication, with old complete dentures worn for more than 10 years (OCDW) and at the final period of the mastication with new complete dentures (NCDW), 5 months after rehabilitation. Twenty‐four asymptomatic subjects (12 DS, 12 CDW) answered a questionnaire based on the Research Diagnostic Criteria for temporomandibular disorders. The CDW group answered the questionnaire before and after new denture insertion and after 5 months of rehabilitation. The SP of the muscles was recorded through EMG at the initial and final periods of mastication using artificial food (Optocal). The operator monitored 35 chewing cycles performed to grind the artificial food and selected eight open‐close‐clench‐chewing cycles for the record. Results: The SP of the muscles analyzed with new complete dentures showed no statistical difference in comparison to the old dentures. There was a statistically significant difference in the SP between the CDW and DS groups for initial and final chewing. Conclusion: Lowered muscular capacity and ability reduced the SP of muscles after rehabilitation with NCDWs.     

Presence of mast cells in various oral mucosal sites in juvenile and adult rats

The present investigation was designed to study the number of mast cells in various oral mucosal sites in juvenile and adult rats, with special reference to presence of subtypes of mast cells. Fifteen juvenile (1-month-old) and 15 adult (6-month-old) rats were used. Biopsies were taken from tongue, bucca, marginal gingiva (incisor area), and intestine (jejunum). For optimal preservation of the stainability of subtypes of mast cells, a fixative with low aldehyde concentration and low pH was used. The biopsies were embedded in paraffinwax. The first of three consecutive sections (5 μ) was stained in toluidine blue for 30 s, the second in toluidine blue for 7 days, and the third in astra blue/safranine. The total number of mast cells was represented by all cells positive to toluidine blue after 7 days' staining, or the sum of cells positive to astra blue and safranine. Cells positive to toluidine blue after 30 s were classified as connective tissue mast cells (CTMCs), and those positive after 7 days, but not after 30 s, as mucosal mast cells (MMCs). Cells positive to safranine in the astra blue/safranine staining sequence were classified as CTMCs, and those positive to astra blue as MMCs. Cells with intermediate staining characteristics in the astra blue/safranine staining sequence were recorded separately. The total number of mast cells in the tongue, buccal mucosa, and gingival mucosa was significantly higher in the juvenile than in the adult rats. In the buccal and gingival mucosa, more than twice as many mast cells were found in the young animals. In the intestine, however, the juvenile rats showed a significantly lower number of mast cells. In general, a higher number of cells with histochemical characteristics similar to the MMCs of the intestine was found in the oral sites of the juvenile animals. The differences in the total number of mast cells and the different composition of the mast cell population in the two age groups may indicate an age-related difference in the potential for biologic reactions involving mast cells.     

Mast cells in oral lichen planus

Biopsies from lichen planus affected oral mucosa were compared with biopsies from healthy oral mucosa, in terms of the number of mast cells, their location and their morphological alteration at the light microscopic and electron microscopic level. In comparison with the normal oral mucosa an increased number of mast cells was found below the subepithelial infiltrate. This difference was statistically highly significant (p < 0.001). In the deeper part of the infiltrate mast cells were found to contain granules which presented an altered morphology upon electron microscopic examination. These cells had many of the ultrastructural changes that have been reported for mast cells undergoing degranulation. The present morphological observations suggest that mast cells participate in the recruitment of lymphocytes to the subepithelial infiltrate.     

Mast cells containing melanin granules in sublingual keratosis

In an ultrastructural study of 3 biopsies taken from the floor of the mouth of 2 patients suffering from sublingual keratosis, it was found that some of the mast cells appearing within the epithelium and connective tissue contained melanin granules which were found to be positive with Masson Fontana stain for melanin. These cells showed all the characteristic features of mast cells and not macrophages. The present results suggest that mast cells have phagocytosed melanin granules and therefore support those views suggesting that mast cells are capable of phagocytosis. They also suggest that not all the cells containing melanin granules and appearing in the lamina propria are the conventional melanophages but some of these may be mast cells.     

Mast cells containing melanin granules in sublingual keratosis

In an ultrastructural study of 3 biopsies taken from the floor of the mouth of 2 patients suffering from sublingual keratosis, it was found that some of the mast cells appearing within the epithelium and connective tissue contained melanin granules which were found to be positive with Masson Fontana stain for melanin. These cells showed all the characteristic features of mast cells and not macrophages. The present results suggest that mast cells have phagocytosed melanin granules and therefore support those views suggesting that mast cells are capable of phagocytosis. They also suggest that not all the cells containing melanin granules and appearing in the lamina propria arc the conventional melanophages but some of these may be mast cells.