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Observational Study
. 2025 Apr 8;25(1):507.
doi: 10.1186/s12903-025-05878-7.

Evaluation of salivary nitric oxide levels and anxiety in multiple sclerosis patients, with and without Xerostomia: correlation with clinical variables

Affiliations
Observational Study

Evaluation of salivary nitric oxide levels and anxiety in multiple sclerosis patients, with and without Xerostomia: correlation with clinical variables

Aynaz Khabazian et al. BMC Oral Health. .

Abstract

Background: Xerostomia is a prevalent but often overlooked condition in multiple sclerosis (MS) patients, significantly impacting their quality of life and oral health. This cross-sectional observational study investigates the role of nitric oxide (NO) in the pathophysiology of multiple sclerosis (MS) and explores its association with xerostomia in MS patients. The primary objective was to compare salivary NO concentrations and stress levels between MS patients with and without xerostomia.

Methods: MS patients diagnosed by neurologists and MRI were categorized into two groups: those with xerostomia and those without. Unstimulated whole saliva samples were collected using the spitting method, and salivary NO levels were quantified using an enzyme-linked immunosorbent assay (ELISA) kit based on the Griess reaction. Stress levels were assessed using the Beck Anxiety Inventory (BAI) questionnaire. The presence of xerostomia was evaluated through the Xerostomia Inventory (XI) and clinical examinations.

Results: Salivary NO levels were significantly higher in MS patients without xerostomia (227.47 ng/mL) compared to those with xerostomia (102.37 ng/mL, p < 0.001). Stress levels were also notably higher in MS patients with xerostomia (17.23) versus those without (11.77, p = 0.03). A moderate negative correlation was observed between salivary NO levels and xerostomia (r = 0.44, p < 0.001), indicating that lower NO levels were associated with a higher likelihood of xerostomia. The correlation between stress levels and xerostomia was weaker but still significant (r = 0.28, p = 0.03). Multivariate binary logistic regression analysis identified salivary NO, stress levels, and age as significant predictors of xerostomia in MS patients. The logistic regression model achieved an 80% accuracy in predicting xerostomia based on salivary NO levels and stress.

Conclusion: This study highlights a significant negative correlation between salivary NO levels and xerostomia, suggesting that decreased salivary NO concentrations are associated with an increased risk of xerostomia in MS patients. Additionally, stress levels were positively correlated with xerostomia, indicating a potential link between higher stress and the likelihood of xerostomia in MS patients.

Keywords: Anxiety; Multiple sclerosis; Nitric oxide; Oral health; Saliva; Stress; Xerostomia.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Tehran University of Medical Sciences Ethical Committee (Ethical code: IR.TUMS.DENTISTRY.REC.1400.185). After the study objectives were described, all the participants signed informed consent before participating in this study. All methods were performed in accordance with the relevant guidelines and regulations and all methods were performed in accordance with the Declaration of Helsinki [49]. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Online version: https://ethics.research.ac.ir/ProposalCertificateEn.php? id=240623&Print=true&NoPrintHeader=true&NoPrintFooter=true&NoPrintPageBorder=true&LetterPrint=true. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
STROBE flow diagram illustrating the enrollment of MS patients with and without xerostomia (STROBE: strengthening the reporting of observational studies in epidemiology)
Fig. 2
Fig. 2
Heatmap showing the correlation coefficients and p values for xerostomia, salivary NO, and other features in MS patients * Other systemic diseases is consist of celiac disease, IBD, and hypothyroidism
Fig. 3
Fig. 3
A) Comparison of salivary NO levels between MS patients with and without xerostomia B) Comparison of stress levels between MS patients with and without xerostomia

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