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Abstract

Introduction

Burning mouth syndrome is a painful condition of the oral cavity with ambiguous pathogenesis and diagnosis. Neuron-specific enolase is increased in several conditions including peripheral neuropathy of diabetes, ophthalmopathies, spinal cord injuries and tumors. Evidence on association of burning mouth syndrome and neuron-specific enolase is limited.

Aim

This study aims to evaluate neuron-specific enolase levels in primary and secondary burning mouth syndrome patients and compare the levels of neuron-specific enolase with associated conditions in secondary burning mouth syndrome.

Methods

One hundred and twenty-eight patients of more than 18 years of age with no gender predilection and having clinical symptoms of burning mouth syndrome and 135 healthy subjects were included. All the patients fulfilled Scala’s criteria for the diagnosis of burning mouth syndrome, including “primary” (idiopathic) and “secondary” (resulting from identified precipitating factors) burning mouth syndrome patients. Blood samples were obtained from burning mouth syndrome patients. Serum neuron-specific enolase was evaluated using enzyme-linked immunosorbent assay. To compare means and standard deviations, among primary and secondary burning mouth syndrome, data was analysed with analysis of variance and multiple comparisons test.

Results

The mean age of the study participants for burning mouth syndrome and healthy subjects was 53.30 and 51.6 years, respectively. Amongst the secondary burning mouth syndrome group, 32 (25%) of the patients had menopause, 15 (11.7%) had diabetes, eight (6.2%) of the patients had nutritional deficiency, seven (5.4%) had combined diabetes, menopause, and depression, six (4.6%) had combined diabetes and depression, four (3.1%) were diagnosed with Sjögren’s syndrome. A minor percentage of 2.3% (three) had gastroesophageal reflux disease, while the remaining three (2.3%) patients in the secondary burning mouth syndrome group were on anti-depressants. There was a statistically significant increase in the levels of neuron-specific enolase in primary burning mouth syndrome as compared to the secondary burning mouth syndrome and healthy groups. Among the subgroups of secondary burning mouth syndrome, diabetic individuals showed a significant increase in neuron-specific enolase level when compared with other conditions in the secondary burning mouth syndrome patients.

Discussion and conclusion: The raised serum neuron-specific enolase levels in patients suffering from primary burning mouth syndrome highlight a possible neuropathic mechanism. It was also increased in the sub-group of secondary burning mouth syndrome patients having diabetes. Although it cannot be ascertained whether the deranged values in the diabetic group were due to burning mouth syndrome or due to diabetes, the raised quantity of neuron-specific enolase in the primary burning mouth syndrome group is a reliable diagnostic indicator. Future studies on the assessment of neuron-specific enolase levels as a diagnostic tool for onset and management of primary and secondary burning mouth syndrome are recommended.

Keywords

Burning mouth syndrome neuron-specific enolase serum diabetes diagnosis biomarker

Introduction

Burning mouth syndrome (BMS) is defined as an intra-oral burning or dysesthesic sensation, recurring daily for more than 2 h/day for more than 3 months, without clinically evident causative lesions (1). The condition has been attributed as a syndrome because of the dysgeusia and subjective xerostomia involved (2). It is a psychologically and physically debilitating condition without a complete cure, owing to its complex pathogenesis and ambiguous diagnosis. Because of the heterogeneity in the symptoms, there is no data on any diagnostic test, imaging technique or other modalities for the definitive diagnosis of BMS. Even the latest advances in the etiology and risk factors of BMS presume the etiology is complex and multifactorial (3). The origin of pathology in the primary form is unknown, whereas there is an inciting factor that gives rise to secondary BMS.

The anterior two thirds of the tongue is the most commonly affected site. Other sites involved, in order of decreasing frequency, are the lateral borders of the tongue, the anterior part of the hard palate and the labial mucosa (1,2). The prevalence of BMS increases considerably with age, with the middle-aged and elderly individuals being largely affected and the prevalence increasing three- to 12-fold with advancing age (4). There is striking female predilection, with females being affected three to seven times more when compared to males (5). The syndrome is relatively rare before the fifth decade and has never been reported in children and adolescents (4). The disease prevalence is impartial to any specific ethnicity or socioeconomic class (5). There is no established set of clinical symptoms that are standardised in all patients suffering from BMS. However, patients usually complain of chronic pain along with burning lasting for 2–3 h a day for a minimum of 4–6 months.

In the last few decades, the most contentious subject in research pertaining to BMS is its pathophysiology. Different authors have contrasting standpoints regarding the underlying pathology responsible for the disease. Whilst some authors postulate BMS is psychogenic (6,7), others believe that it is due to subclinical inflammation (8 –10) while still others have posited that it is neurogenic (11). Some researchers have concluded that BMS is not an aftermath of a single factor (12). Nonetheless, there are multiple factors interplaying to generate BMS symptoms (12,13). The most widely accepted theory on etiopathogenesis of BMS points towards a neuropathic involvement (11). Various psychophysical, neuropathological, neurophysiologic and functional imaging studies have postulated the subclinical involvement of neuraxis at different levels (14). Lauria et al. were one of the first researchers who took biopsies from the anterior two-thirds of the tongues of patients suffering from BMS, to discover small-fiber sensory neuropathy (14). They reported the presence of axonal degeneration in epithelial and sub-papillary nerve fibers in the anterior two-thirds of the tongue (14). Although the neuropathological mechanism responsible for BMS postulated varies, there is consensus in literature on the fact that the pathophysiologic alterations occurring in the nervous system cannot be diagnosed on clinical grounds alone. It is imperative to carry out confirmatory tests in order to identify the pathology and pinpoint the subgroup of BMS the patient belongs to. A common reason proposed for the painful sensations in BMS is a decrease in the density and change in the morphology of oral epithelial and sub-epithelial nerve fibres (15). A trigeminal small-fibre sensory neuropathy or axonopathy is predicted, since the morphologic changes are consistent with axonal degeneration (14). This axonal damage could lead to a rise in the levels of neuron-specific enolase (NSE) by mechanisms similar to diabetic neuropathy (16,17).

NSE is an intracellular enzyme with a principal location in the cytoplasm of neuroendocrine cells and the central and peripheral neurons. NSE is present in the body fluids in insignificant amounts (4–12 μg/L) in physiological conditions, where it is responsible for survival, differentiation and regeneration of neurites and neurons. NSE performs its physiological functions by activation of phosphatidylinositol 3‐kinase (PI3K) and mitogen‐activated protein (MAP) kinase signal transduction pathways. However, its secretion increases after neuronal damage, following which it is released into the blood and cerebrospinal fluid. NSE is regarded as a useful biomarker in assessing functional damage to neurons according to multiple reports (16,18,19).

BMS adversely impacts the quality of life of patients by having a negative influence on their physical and psychological health. Prior to a confirmatory diagnosis, patients are known to have been attending neurologists, dentists, general practitioners, dermatologists, psychologists and gastroenterologists. The availability of a specific serum biomarker would make the diagnosis more objective and precise. Once a definite marker for BMS is identified, a standard diagnostic procedure can be suggested, which could further assist in effective management planning. The serum NSE parameter could be a viable option for the objective diagnosis of burning mouth syndrome, the diagnosis of which is largely based on patient symptoms.

It is hypothesised that serum NSE would be higher in patients with secondary BMS as compared to patients with primary BMS and that the levels of NSE may be associated with clinical conditions in secondary BMS. Therefore, this study aims to evaluate NSE levels in primary and secondary BMS patients and compare the levels of NSE with associated conditions in secondary BMS.

Materials and methods

The present study followed the guidelines and reporting checklist described in the STROBE statement and conforms to the principles of the Declaration of Helsinki. This was a case-control study where study participants were recruited from the Outpatient Department of Oral Diagnosis, Ziauddin College of Dentistry, Ziauddin University, Karachi and Civil Hospital, Karachi, Pakistan. Using a prevalence of 4% (8,13,24), a total of 128 participants in the BMS group were recruited in this study by estimating sample size with power of 90% and 95% confidence interval. Patients were requested to sign an informed consent and were allowed to exit the study without any consequences.

Ethical statement

Approval was obtained from the Ethics Review Committee of Ziauddin University, Karachi, Pakistan (Reference code: 0641118JKOM). The complete procedure was explained to all the study participants prior to the commencement of the study and the aforementioned written consent was taken from each study participant.

Study participants

One hundred and twenty-eight patients of more than 18 years of age with no gender predilection and having clinical symptoms of BMS and 135 patients as healthy controls were included. Patients with known malignancies and/or nervous system diseases were excluded from the study. Patients with “primary” (idiopathic) and “secondary” (resulting from identified precipitating factors) BMS fulfilling Scala’s criteria for the diagnosis of BMS were included in the study (20). Scala’s criteria include a) daily deep burning sensation of oral mucosa (bilateral); b) pain for at least 4–6 months; c) constant intensity or increasing intensity of pain/burning during the day; d) characteristic symptoms are not getting worse/sometimes there may be an improvement over the ingestion of food and liquid; e) no interference with sleep.

Study procedures

Patients were asked to fill out an interview-based questionnaire. The contents of the questionnaire included personal details, demographics, medical history, medication history, past dental history and dental visits. The second section of the questionnaire was completed by the operator by undertaking full mouth intra- and extra-oral examination. A detailed record was made of the number of teeth, decayed, filled or missing teeth and prosthesis present. Under soft tissue examination, the tongue, soft and hard palate, and the labial and buccal mucosa were examined for red or white lesions, lacerations, ulcerations, pigmentations, or swellings.

Following the clinical examination, the patients were seated in a comfortable position and apprised with the final step. Asepsis was achieved using a sterile alcohol swab on the left hand of the patient. Five millilitres of blood was slowly drawn and a dry piece of sterile cotton wool was placed with firm pressure for hemostasis. The contents of the syringe were then transferred into a labelled yellow-top tube. The whole blood was allowed to clot by leaving it undisturbed for 30 min at room temperature. The clot was then removed by centrifuging at 3000 rpm for 10 min in a refrigerated centrifuge (ThermoFisher Scientific, USA) to obtain serum. The obtained serum was then transferred into labelled Eppendorf tubes using micropipettes and the samples were stored at −80°C until sufficient samples were collected.

Neuron-specific enolase (NSE) assessment

Enzyme-linked immunosorbent assay (ELISA) was carried out using a Cloud-clone Human NSE kit (Cloud-Clone Corp. Product#: SEA537Hu). All the kit components and samples were kept to room temperature (18–25°C) before use. To prepare the Standard, it was reconstituted with 0.5 mL of standard diluent, which was kept for 10 min at room temperature. Seven tubes were prepared containing 0.25 mL standard diluent with the concentration halving with each subsequent tube. The final concentrations of the standard in the seven tubes were 40 ng/mL, 20 ng/mL, 10 ng/mL, 5 ng/mL, 2.5 ng/mL, 1.25 ng/mL and 0.625 ng/mL. Detection Reagent A and Detection Reagent B were prepared by centrifuging the stock reagents followed by diluting them 100-fold with their respective assay diluents.

Statistical analysis

Data analysis was performed using Statistical Package for the Social Science (SPSS) version 20 and a p-value of <0.05 was taken as significant. Mean and standard deviation was computed for quantitative variables whereas frequencies and percentages were evaluated for categorical variables. Inter-group difference of biomarker level between primary, secondary BMS and healthy controls were evaluated using one-way analysis of variance (ANOVA). ANOVA and Student’s t-test was used to compare the association between different types of BMS.

Results

One hundred and twenty-eight participants for BMS and 135 for healthy controls were recruited in this study. The BMS participants were divided into primary (39%) and secondary (61%) BMS. Secondary BMS patients were distributed into eight categories according to the comorbid conditions including menopause, gastroesophageal reflux disease (GERD), nutritional deficiencies, Sjögren’s syndrome, patients on anti-depressants, diabetes, diabetes with depression, menopause with diabetes and depression.

Demographics

The overall age range of patients included in this study was 28–92 years, of which 46.6% (60) were in the age range of 46–60 years and 40% (68) of the participants fell in the age range of 31–45 years. The mean age and gender distribution for all the groups are presented in Table 1. The mean age of the BMS and healthy participants was 53.3 and 51.6 years, respectively. Eighty-two participants were females and 46 were males in the BMS group, while 94 participants were females, and 41 participants were males in the healthy control group.

Table 1.

Demographic details of the study participants.

Characteristics	BMS	Healthy control
Total sample size, n	128	135
Gender, n (M/F)	46/82	41/94
Mean age (±SD)	53.3 ± 12.5	51.6 ± 11.3

SD: standard deviation; n: sample size; M: male; F: female.

Sample categorization according to Scala

Out of 128 patients, 50 (39%) patients suffered from primary BMS while 78 (61%) patients had secondary BMS (20). Amongst the secondary BMS group, 25% had menopause, 11.7% had diabetes, 6.2% suffered from nutritional deficiency, 5.4% had diabetes, menopause, and depression, 4.6% had diabetes and depression, and 3.1% were diagnosed with Sjögren’s syndrome. Three (2.3%) participants with secondary BMS had GERD and three (2.3%) were on anti-depressants respectively (Table 2).

Table 2.

Mean biomarker level according to Scala’s classification.

BMS classification	Number of cases, n (%)	Mean NSE level (µg/L ± SD)
Healthy control	135 (100)	1.84 ± 0.77
Primary (No associated condition)	50 (39)	16.24 ± 3.38
Secondary
Menopause	32 (25)	6.23 ± 1.42
GERD	3 (2.3)	9.89 ± 1.81
Nutritional deficiency	8 (6.25)	6.10 ± 0.84
Sjögren’s syndrome	4 (3.12)	5.31 ± 0.57
Anti-depressants	3 (2.3)	8.78 ± 1.56
Diabetes	15 (11.7)	16.38 ± 1.75
Diabetes + antidepressant	6 (4.6)	17.23 ± 1.70
Diabetes + menopause + antidepressant	7 (5.4)	17.85 ± 3.59

µg/L: micrograms per liter; SD: standard deviation.

Serum NSE levels

The mean NSE in healthy control subjects was 1.84 µg/L. The mean NSE level in primary BMS patients was 16.24 ± 3.38 µg/L, whereas in secondary BMS it was 8.52 ± 4.41 µg/L (Table 3). The levels were higher than the physiological range in the primary BMS patients, whereas the levels of NSE in the secondary group fell within the normal range. There was a significant difference in the NSE levels among healthy controls and primary and secondary BMS patients (p = 0.001).

Table 3.

Inter-group difference of biomarker level between primary and secondary BMS.

Variables	Biomarker level (µg/L)	p-value*
Healthy control	1.84 ± 0.77	0.001
Primary	16.24
Secondary	8.52

Note: p-value of <0.05 was considered significant using Mann-Whitney U test.

Intra-group comparisons of biomarker levels among sub-groups of secondary BMS are reported in Table 4. It was observed that all the secondary BMS patients having diabetes (p < 0.001), diabetes + antidepressants (p < 0.001) and diabetes + anti-depressants +menopause (p < 0.001) showed significantly higher NSE levels compared to other subgroups (Table 4).

Table 4.

Intra group comparison of biomarker level among sub-groups of secondary BMS.

NSE levels	Associated conditions	P-value
Diabetes	Menopause	0.001
	GERD	0.001
	Nutritional deficiency	0.001
	Sjögren’s syndrome	0.001
	Antidepressants	0.001
	Diabetes + antidepressants	0.99
	Diabetes + antidepressants + menopause	0.80
Menopause	GERD	0.08
	Nutritional deficiency	1.00
	Sjögren’s syndrome	0.99
	Antidepressants	0.47
	Diabetes + antidepressants	0.001
	Diabetes + antidepressants + menopause	0.001
GERD	Nutritional deficiency	1.35
	Sjögren’s syndrome	0.83
	Antidepressants	0.99
	Diabetes + antidepressants	0.001
	Diabetes + antidepressants + menopause	0.001
Nutritional deficiency	Sjögren’s syndrome	0.99
	Antidepressants	0.56
	Diabetes + antidepressants	0.001
	Diabetes + antidepressants + menopause	0.001
Sjögren’s syndrome	Antidepressants	0.37
	Diabetes + antidepressants	0.001
	Diabetes + antidepressants + menopause	0.001
Antidepressant	Diabetes + antidepressant	0.001
Antidepressant	Diabetes + antidepressants + menopause	0.001
Diabetes + antidepressant	Diabetes + antidepressants + menopause	1.11

Note: p-value of <0.05 was considered significant.

NSE levels among secondary BMS patients with menopause (6.23 ± 1.42), GERD (9.89 ± 1.81), nutritional deficiency (6.10 ± 0.84), Sjögren’s syndrome (5.31 ± 0.57), and anti-depressants (8.78 ± 1.56) were statistically comparable (p > 0.05) (Tables 2 and 4). In addition, NSE levels among patients on anti-depressants alone were significantly lower compared to NSE levels of patients on anti-depressants with diabetes (17.23 ± 1.70) and patients on anti-depressants with menopause (17.85 ± 3.59).

Inter-group comparisons of biomarker levels between primary and sub-groups of secondary BMS are reported in Table 5. A statistically significant difference was noted when mean levels of serum NSE in primary BMS were compared with secondary BMS associated with menopause, GERD, nutritional deficiency, Sjögren’s syndrome and patients taking anti-depressants (p < 0.001). in addition, the levels of NSE were comparable between primary BMS and diabetes (p = 1.00), diabetes + anti-depressants (p = 0.99) and diabetes + menopause + anti-depressants (p = 0.76).

Table 5.

Inter-group comparison of biomarker level between primary and sub-groups of secondary BMS.

	Secondary BMS	p-value
Primary BMS (no associated condition)(16.24 ± 3.38)	Menopause(6.23 ± 1.42)	0.001
	Diabetes(16.38 ± 1.75)	1.00
	GERD(9.89 ± 1.81)	0.001
	Nutritional deficiency(6.10 ± 0.84)	0.001
	Sjögren’s syndrome(5.31 ± 0.57)	0.001
	Antidepressants(8.78 ± 1.56)	0.001
	Diabetes + antidepressants(17.23 ± 1.70)	0.99
	Diabetes + menopause +antidepressants(17.85 ± 3.59)	0.76

Note: p-value of <0.05 was considered significant.

Discussion

The present study aimed to evaluate NSE levels among healthy controls and primary and secondary BMS patients and compare the levels of NSE with associated conditions in secondary BMS. The outcomes of the study showed a significant increase in the levels of NSE in primary BMS compared to the secondary BMS and healthy patients. Among the subgroups of secondary BMS, patients having diabetes showed significantly increased NSE levels when compared with other conditions in the secondary BMS. This study potentially associates increased levels of a serum biomarker in the form of NSE with primary and secondary BMS.

Burning mouth syndrome is a disease with complex pathogenesis, that compromises the quality of life with major psychological implications. The clinical manifestation of BMS suggests that anxiety, stress, depression, and other psychological conditions lead to sensations of burning and pain in the oral cavity. Studies indicate that endocrinological, immunological and inflammatory biomarkers are either up-regulated or down-regulated in the serum (20 –22). However, there have been no studies that identified the exact etiology of BMS at the molecular level.

In the present study, the mean age of the population was 53 years and 60% of our patients were aged between 46 and 65 years. This was in accordance with studies by Kohorst et al. and Riordain et al., who stated that there is a sharp increase in BMS incidence after the fifth decade of life (21,22). Sixty-four percent of the patients in our study were females, which was in keeping with previous studies that state that there is a female preponderance in BMS (8,22,23). The high ratio of females to males can be attributed to the fact that females seek dental advice and attention more frequently than males. Secondly, females experience a fluctuation of hormones in the perimenopausal age, which contributes to the pain and burning experienced in burning mouth syndrome (23,24). Out of a total of 128 patients included, 50 (39%) had primary BMS while 78 (61%) had secondary BMS, complaining of morbidities along with BMS. This data was also heterogeneous in various studies since some articles included only primary BMS (25,26), some exclusively secondary BMS (27), while others did not categorise their patients as primary or secondary (28). Among the secondary BMS category, the highest number of patients had menopause (25%) as an associated and causative condition leading to BMS. This finding was similar to previous reports where menopausal women comprised a large number of the study population (27,29). Although the exact cause is unclear, it is suggested that the dysregulation of gonadal steroids in menopause causes an alteration in the production of neuroactive steroids in skin and mucosa that leads to symptoms of pain and burning (30). This hypothesis remains questionable since hormone replacement therapy in menopause proves to be of little help in reducing the symptoms of BMS (31). The second possibility that has been proposed in these patients is that the change in contents, pH, amount and viscosity of saliva contributes to BMS symptoms (32,33).

In our study, 6.2% of the patients had a known deficiency of vitamin B12. B12 deficiency causes a clinical minor atrophy of the tongue epithelium, allowing an easy access for irritants through the atrophic epithelium. This sensitizes the free nerve endings and causes pain and burning (34). In addition, 2.3% of the included patients were diagnosed cases of GERD. BMS in GERD can be because of direct contact of acid with the mucosal surfaces that may eventually result in erythema of the soft tissues (35). However, the patients in the current study had a clinically normal mucosa. This could be explained by the fact that GERD may also cause a reduction in salivary flow as well as a change in the buffering capacity of saliva, which could contribute to pain and burning (36). Sjögren’s syndrome was a comorbidity in 3.1% of the study population. Sjögren’s syndrome is a connective tissue disorder wherein the innate immunity of the body is dysregulated. Reduction in salivary flow is a hallmark of Sjögren’s syndrome, leading to xerostomia (37). This may lead to burning and pain, with or without other clinical changes. It could also be conceived that oral burning and pain could be a result of Sjögren’s syndrome-associated neuropathies (38). In the present study, 2.3% of the subjects were suffering from psychosomatic conditions and hence taking antidepressants. Depression, anxiety, and stress produce an anticholinergic affect in the body, reducing the salivary content (39). Additionally, use of antidepressants also causes hyposalivation, precipitating the pain and oral burning (40). Barry et al. proposed yet another plausible hypothesis, stating that disruption of the cytokine profile, particularly that of IL-8, potentially correlates with depressive symptomatology of BMS (8).

When the mean NSE level was calculated for the entire study population, a value of 9.40 ± 4.50 µg/L was obtained. It is suggested that normal serum NSE levels ranges from 4 to 12 μg/L among healthy individuals (41). This is the first time that serum NSE has been assessed in BMS, therefore a comparison is not possible. As observed in the present study, the mean level of NSE in primary BMS was higher (16.24 ± 3.38 µg/L) than the normal range (4–12 µg/L), while in the secondary BMS group NSE levels fell (8.52 ± 4.41 µg/L) within the normal range. NSE levels in primary BMS patients were significantly higher than the levels in secondary BMS patients overall. This increase in serum NSE can be attributed to neuronal degeneration in primary BMS. This is in line with studies by Lauria et al. (14) and Yilmaz et al. (42), who pioneered the discovery of neural fiber loss in oral tissues for BMS. As a result, various authors provided evidence of peripheral nerve degeneration in BMS (11,43). It has been observed that neurons under various types of stress like neuronal repair, neuronal damage, and neuronal death release NSE to compensate for the increased energy demands (44). We postulate that disruption in the nerve damage and nerve repair in BMS balances in favour of nerve damage, causing an upsurge of NSE to meet the increased demand of glycolysis. The reason postulated for the normal NSE level in the secondary group is that some conditions associated with secondary BMS like GERD, nutritional deficiency, and menopause show a non-neuronal pathway that leads to an overall stable NSE mean value.

In the present study, comparing the levels of NSE in primary BMS with that of secondary BMS associated with diabetes, it was observed that levels of NSE were comparable. Although it is not clear whether the increased levels in the secondary BMS associated with diabetes are due to burning mouth syndrome or diabetes, it can be implied that diabetic neuropathy, which is a sequel of long-standing diabetes, plays a role in BMS pathogenesis (45). Previous researchers observed hyposalivation as well as presence of oral Candida growth in diabetes (46), both of which stimulate symptoms and manifestations of BMS. Contradicting these findings, it is suggested that BMS symptoms in diabetes are a consequence of peripheral neuropathy (25,47,48), which occurs due to a microangiopathy of nerve fibres causing a chronic impairment of nerve conduction (49). Neuropathy in the oral region can cause impairment of taste, which is possibly responsible for the symptom of altered taste sensation in BMS (50). Literature has previously identified serum NSE as a potential biomarker associated with diabetic neuropathy, retinopathy, and ketoacidosis (17,51 –54).

Some limitations exist in the present study. The estimation of oral health-related quality of life and their association with the biomarker levels may have resulted in the assessment of patient’s degree of comfortability and ability to participate in daily routine life. This case-control study could not identify the exact cause of elevated NSE levels. There could have been a possibility of neuronal regeneration via central mechanisms involving BMS contributing to the elevated NSE levels. Since diabetes was a lateral finding, we did not have sufficient data regarding the type, duration and severity of the disease and therefore it could not be associated with NSE levels. The underlying medical conditions were identified through a self-reported questionnaire only. Since this was a case-control study, the chicken-egg conundrum was involved and it could not be ascertained whether BMS caused the increase in NSE or vice versa. Since this study was done cross-sectionally, the exact cause of disrupted NSE levels could not be identified. Furthermore, future longitudinal clinical trials should be conducted to assess the evolution of changes in the biomarker levels, both at the salivary and serum levels among BMS patients to assess the pattern of the disease at oral and systemic level.

Conclusion

Although the levels of NSE were within the physiological range in patients suffering from secondary BMS, there was a significant increase in serum NSE in individuals having primary burning mouth syndrome, highlighting a possible neuropathic mechanism involved. It was also increased in the sub-group of secondary BMS patients having diabetes. Future studies on the marker could further validate its importance in the diagnosis of burning mouth syndrome.

Clinical implications

There is an increase in serum NSE in individuals having primary burning mouth syndrome, highlighting a possible neuropathic mechanism.

Serum NSE may serve as a potential biomarker associated with BMS.

BMS symptoms in diabetes are possibly a consequence of peripheral neuropathy.

Footnotes

Ethics approval and patient consent

Approval was obtained from the Ethics Review Committee of Ziauddin University, Karachi, Pakistan (Reference code: 0641118JKOM). The ethical standards of the 1964 Helsinki declaration and national and/or institutional research committee were strictly followed while performing all the procedures. Informed written consent was obtained from each subject before conducting any procedures. Additional information on the study was provided verbally by the study investigator or in a written format.

Acknowledgment

The authors are grateful to the Researchers supporting project at King Saud University for funding through Researchers supporting project No. (RSP-2019-44)

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors are grateful to the Researchers supporting project at King Saud University for funding through Researchers supporting project No. (RSP-2019-44).

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Evaluation of serum neuron specific enolase levels among patients with primary and secondary burning mouth syndrome

Abstract

Introduction

Aim

Methods

Results

Keywords

Introduction

Materials and methods

Ethical statement

Study participants

Study procedures

Neuron-specific enolase (NSE) assessment

Statistical analysis

Results

Demographics

Sample categorization according to Scala

Serum NSE levels

Discussion

Conclusion

Clinical implications

Footnotes

Ethics approval and patient consent

Acknowledgment

Declaration of conflicting interests

Funding

References