Xerostomia correlates with pain sensitivity in burning mouth syndrome patients

Abstract

Patients with burning mouth syndrome (BMS) often exhibit abnormal somatosensory function, and xerostomia is a common accompanying symptom. This study aimed to explore whether xerostomia is associated with pain sensitivity in patients with BMS. A total of 82 female patients with BMS were enrolled, including 55 with xerostomia. The pressure pain threshold (PPT) on the tongue was measured via a digital pressure algometer. Pain sensitivity was assessed via the Pain Sensitivity Questionnaire (PSQ). Whole saliva flow rates were measured. The severity of xerostomia was evaluated via the Summated Xerostomia Inventory (SXI). Descriptive statistics were performed, along with chi-square tests, Pearson correlation analyses, and multiple linear regression analyses. There were no significant differences in the PPT or stimulated saliva flow rates between BMS patients with and without xerostomia (112 ± 53 vs. 129 ± 57, p = 0.5837; 1.55 ± 0.73 vs. 1.64 ± 0.62, p = 0.5837, respectively). BMS patients with xerostomia had significantly higher PSQ-minor scores (4.55 ± 1.36 vs. 3.93 ± 1.11, p = 0.0432 < 0.05). PSQ-minor scores were correlated with the duration of xerostomia (β = 0.399, p = 0.003) but not with the severity of xerostomia. Xerostomia had different effects on the two pain sensitivity dimensions in patients with BMS: there was no significant change in the experimentally obtained pain threshold, while the self-assessed suprathreshold pain intensity increased.

Introduction

The International Headache Society (IHS) defines burning mouth syndrome (BMS) as “a burning sensation in the mouth for which no medical or dental cause can be found”¹. The aetiology of BMS is multifactorial and unclear; it is potentially mediated by neuropathic pain arising from varying degrees of peripheral and central nervous system dysfunction². With a prevalence of 3.31% in populations over 50 years old, BMS is relatively common and primarily affects perimenopausal and postmenopausal women, significantly impacting their quality of life^3,4. Burning pain in the tongue or other oral mucous membranes is the primary complaint of BMS patients⁵. Pain perception is a subjective and multidimensional experience, exhibiting considerable individual variability⁶. The intensity of perception to painful stimuli (in daily life, clinically, or experimentally) is often abstracted to reflect an individual’s “pain sensitivity” compared with other members of a group. Pain sensitivity has proven to be a useful concept in clinical and experimental pain research and is useful for predicting acute postoperative pain in individuals. Furthermore, patients with idiopathic chronic pain disorders generally exhibit increased pain sensitivity, a finding that has facilitated the exploration of the pathophysiology of these conditions^7,8. Studies have shown that BMS patients have somatosensory dysfunction both intraorally and extraorally, although quantitative sensory testing results are inconsistent². It has been reported that pain sensitivity in BMS patients may be related to factors such as anxiety, sleep quality, and sociodemographic variables⁹.

Xerostomia is a subjective sensation of oral dryness, which may be related to hypofunction of the salivary glands. However, only 37% of patients with xerostomia actually have decreased saliva flow rates¹⁰. Xerostomia is primarily assessed via questionnaire scales¹¹. Earlier studies have suggested a correlation between sensory changes in the oral mucosa and oral dryness¹². A previous animal study reported that rats with dry tongues exhibit mechanical hyperalgesia¹³. Subjects wearing complete dentures with xerostomia exhibit increased pressure pain sensitivity in the oral mucosa¹⁴. Approximately 25% of BMS patients experience xerostomia¹⁵. To our knowledge, there are few reports on whether xerostomia is correlated with somatosensory function changes in BMS patients.

In this study, we compared pain sensitivity measures between groups and explored their associations with dry mouth. To distinguish between the pain threshold and pain intensity assessment dimensions of pain sensitivity, we used the experimental pressure pain threshold (PPT) and a self-reported pain sensitivity questionnaire (PSQ-minor score), respectively. The pressure pain threshold (PPT) is defined as the minimum pressure that elicits pain and has been used in some studies to measure pain sensitivity in the oral mucosa¹⁶. The PSQ-minor scores are based on pain intensity ratings of imagined painful daily life situations and have been shown to be highly correlated with experimental pain intensity perception but not with experimental pain thresholds¹⁷. We hypothesized that xerostomia is associated with changes in sensory function in BMS patients and that BMS patients with xerostomia have greater pain sensitivity than those without xerostomia.

Methods

Participants

A cross-sectional study was conducted at the Stomatological Medical Center of the First Affiliated Hospital of Zhengzhou University from June 2023 to August 2024. The study was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of Zhengzhou University (2023-ky-1298). All the participants gave their informed consent and all methods were performed in accordance with the relevant guidelines and regulations.

BMS patients were recruited via convenience sampling. The inclusion criteria for the diagnosis of BMS in this study were as follows^9,18,19: (1) intraoral burning or dysesthesia daily for > 2 h/day for > 3 months; (2) patients may have had other subjective symptoms (such as xerostomia, oral paresthesia and taste disorders); (3) no obvious oral lesions were observed; and (4) there was a lack of evidence for a specific etiology that may cause the oral burning sensation, such as trigeminal neuralgia, diabetes, malnutrition, and connective tissue disease. Patients who are unable to understand or complete the questionnaire, have a history of mental, neurological, or organic brain diseases, have a history of alcohol or drug abuse, or are currently receiving psychotropic medications or systemic medications that may be related to oral symptoms will be excluded.

An a priori power analysis was conducted via G*Power Version 3.1.9.2, which indicated that a sample size of 82 BMS patients (55 with xerostomia and 27 without xerostomia) would be needed to achieve a power level of 0.95, with a significance level of no more than 5% and an effect size value of 0.77²⁰.

Pain sensitivity assessment

The Pain Sensitivity Questionnaire (PSQ) is a self-assessment tool for evaluating pain sensitivity that has been validated in both healthy subjects and patients with chronic pain^17,21. The PSQ consists of 17 items, each describing a daily life situation and requiring participants to rate how painful that situation is for them via a numerical rating scale (NRS) ranging from 0 (not painful at all) to 10 (the most intense pain). Since previous studies have shown that PSQ-minor scores may be equally or more strongly correlated with experimental pain tests than the PSQ-total score is¹⁷, only the PSQ-minor score was analysed in this study. The Mandarin version of the PSQ has undergone formal reliability and validity checks²².

The pressure pain threshold (PPT) was measured via a digital pressure algometer (YISHENG VICTOR TECH CO. LTD., Shenzhen, China; Model: − 50, Range: 0–50 N). Each participant sat in a dental chair with their head supported by a headrest. One of the trained examiners applied a 1 cm² rubber tip to the participant’s tongue tip, and during the test, the pressure increased at a rate of 50 kPa/s²³. When the stimulation became painful, the participant signalled, and the pressure was immediately released. The process was repeated three times, with a 3-min interval between each measurement. The PPT was determined as the average of the three recordings. A lower PPT indicates greater pain sensitivity.

Oral dryness assessment

The subjective degree of oral dryness was assessed via the Summated Xerostomia Inventory (SXI), which includes the following five questions: “My mouth feels dry,” “I have difficulty eating dry foods,” “My mouth feels dry when eating a meal,” “I have difficulties swallowing certain foods,” and “My lips feel dry.” The participants were asked to rate each item via a three-point Likert scale, where 1 indicates “never,” and 3 indicates “always.’ The total SXI score is the sum of the five individual scores, ranging from 5 to 15, with higher scores indicating more severe dry mouth²⁴. On the basis of these scores, the degree of dry mouth was classified as follows: 5, no dry mouth; 6–8, mild dry mouth; 9–12, moderate dry mouth; and 13–15, severe dry mouth.

Objective salivary flow rate measurements were conducted according to previously validated methods, following standardized procedures to assess total salivary flow at rest and during stimulation²⁵. All participants were instructed not to consume any food or beverages (except water) for 1 h before the test. To avoid the influence of diurnal rhythms, collections were performed between 9:00 AM and 12:00 PM. Unstimulated whole saliva (USWS) was collected first, followed by stimulated whole saliva (SWS) collected after 3 min of chewing a sugar-free lemon-flavoured candy. The participants spit the saliva into preweighed tubes, with each collection lasting for 5 min.

Statistical analysis

All analyses were performed via SPSS software version 22.0 (SPSS Corporation, Chicago, Illinois, USA). Descriptive statistical methods were used to summarize the clinical characteristics and oral-related symptom features of the BMS patients. Continuous variables are presented as the means (+ /− SD) and ranges (minimum–maximum) for patient characteristics, whereas categorical variables are presented as frequencies and percentages. Pearson correlation analysis was conducted to determine the correlation between pain sensitivity indicators and xerostomia. Multiple linear regression was used to assess the impact of these clinical factors as independent variables on the dependent variable, the PSQ-minor score. The R² value represents the explanatory power of the regression model. The independence of residuals was calculated via the Durbin–Watson statistic, and values close to 2 indicate no issues with the independence assumption. The variance inflation factor (VIF) was used to evaluate multicollinearity, with a VIF > 5 indicating high multicollinearity.

Results

A total of 82 female patients with burning mouth syndrome (BMS) were included in this study to eliminate sex differences (Table 1). All patients complained of typical burning pain. On the basis of the presence of subjective oral dryness, patients were divided into a dry-mouth group and a nondry-mouth group. There were no significant differences between the two groups in terms of age, menstrual status, average body mass index, or pain duration. In the dry-mouth group, the average duration of xerostomia was 7.33 ± 1.34 months, with 23.64% of patients having symptoms for more than 12 months and the longest duration being 19 months. The average SXI score was 7.75 ± 1.34, with 72% of patients scoring below 8, indicating mild dry mouth in most cases. Compared with that in the nondry-mouth group, the resting salivary flow rate in the dry-mouth group was significantly lower (0.22 ± 0.17 vs. 0.32 ± 0.21, p = 0.0233 < 0.05), whereas there was no significant difference in the stimulated salivary flow rate (1.55 ± 0.73 vs. 1.64 ± 0.62, p = 0.5837). The PSQ-minor scores were significantly greater in the dry-mouth group than in the nondry-mouth group (4.55 ± 1.36 vs. 3.93 ± 1.11, p = 0.0432 < 0.05). Although the PPT was lower in the dry-mouth group than in the nondry-mouth group, the difference was not statistically significant (112 ± 53 vs. 129 ± 57, p = 0.5837). The dry-mouth group had significantly greater self-rated pain sensitivity than the nondry-mouth group did, while there was no significant difference in mechanical pain sensitivity on the tongue. To explore the factors influencing PSQ-minor scores in BMS patients with xerostomia, Spearman’s rank correlation coefficient was used to study the correlation between PSQ-minor scores and unstimulated whole saliva (UWS), stimulated whole saliva (SWS), SXI scores, and PPT in the dry-mouth group (Table 2). The study revealed a significant positive correlation between the duration of dry mouth and the PSQ-minor score (r = 0.309, p = 0.022 < 0.05). That is, the longer the duration of dry mouth is, the higher the PSQ-minor score is, indicating greater pain sensitivity in patients. Multiple linear regression analysis was performed to investigate the impact of the UWS, SWS, SXI score, and PPT on the PSQ-minor score in BMS patients with xerostomia (Table 3). The regression analysis results revealed that the regression equation was significant (F = 10.008, p = 0.003 < 0.05). Among them, a dry mouth duration of more than 12 months significantly positively predicted PSQ-minor scores (β = 0.399, p = 0.003).

Table 1.

Clinical characteristics of BMS patients.

Variables	BMS (n = 55) with xerostomia	BMS(n = 27) without xerostomia	p-value
Age (years)a	59.5 ± 11.7	56.6 ± 10.3	0.2765
Menopauseb	78.3%	70.4%	0.4389
Body Mass Indexa	26.2 ± 3.62	27.1 ± 2.49	0.2486
Pain duration (months)a	9.7 ± 8.3	9.2 ± 7.5	0.7922
PSQ-minora	4.55 ± 1.36	3.93 ± 1.11	0.0432*
PPTa	112 ± 53	129 ± 57	0.1868
UWS (ml/min)a	0.22 ± 0.17	0.32 ± 0.21	0.0233*
SWS (ml/min)a	1.55 ± 0.73	1.64 ± 0.62	0.5837
SXI	7.75 ± 1.34	–
Xerostomia duration	7.33 ± 5.11	–
≤ 6 months	28(50.91%)	–
> 6 months, and ≤ 12 months	14(25.45%)	–
> 12 months	13(23.64%)	–

PSQ, pain sensitivity questionnaire; BMS, burning mouth syndrome; PPT, pressure pain threshold; UWS, unstimulated whole saliva; SWS, stimulated whole saliva; SXI, Summated Xerostomia Inventory. ^at-test, ^bPearson’s chi-squared test. *p < 0.05.

Table 2.

Associations with PSQ-minor scores in BMS patients with xerostomia.

	UWS	SWS	SXI	PPT	Xerostomia durations
PSQ-minor
r	− 0.156	− 0.149	0.030	− 0.174	0.309
p	0.128	0.138	0.413	0.102	0.022*

PSQ, pain sensitivity questionnaire; BMS, burning mouth syndrome; PPT, pressure pain threshold; UWS, unstimulated whole saliva; SWS, stimulated whole saliva; SXI, Summated Xerostomia Inventory. r represents Pearson’s correlation coefficient. *p < 0.05.

Table 3.

Multiple linear regression for BMS patients with oral dryness in relation to UWS, SWS, SXI, PPT, and xerostomia durations.

	PSQ-minor
	B	SE	β	t	P	VIF
Constant	29.762	1.361		21.874	0.000
Xerostomia durations
> 12 months	8.853	2.799	0.399	3.164	0.003*	1.00
UWS	− 0.163	− 1.298	0.2	1.001
SWS	− 0.129	− 1.028	0.309	1.001
SXI	0.003	0.025	0.980	1.000
PPT	− 0.048	− 0.361	0.720	1.094
Xerostomia durations
6 < and ≤ 12 months		− 0.023	− 0.172	1.118	1.118
F = 10.008 (P = 0.003), R2 = 0.159, adR2 = 0.143, D–W = 1.929

PSQ, pain sensitivity questionnaire; BMS, burning mouth syndrome; PPT, pressure pain threshold; UWS, unstimulated whole saliva; SWS, stimulated whole saliva; SXI, summated Xerostomia Inventory; B, regression coefficient; SE, standard error; β, beta; t, tolerance; VIF, variance inflation factor; D–W, Durbin–Watson statistic.

*p < 0.05.

The data were analyzed by the multiple linear regression.

Discussion

Pain is the primary complaint of BMS patients, and increased pain intensity is significantly associated with increased depression and anxiety²⁶. The greater the patients’ sensitivity to pain is, the lower their quality of life¹⁹. In our study, we found that BMS patients with dry mouth had significantly higher PSQ-minor scores and increased pain sensitivity. The duration of dry mouth was a predictor of pain sensitivity in patients with BMS, indicating that the longer dry mouth is experienced, the greater the pain sensitivity of patients with BMS. To our knowledge, we are the first to report that long-term xerostomia may increase pain sensitivity in BMS patients.

Xerostomia (or oral dryness) is a major complaint of many BMS patients and is associated with unpleasant sensations in the mouth and throat²⁷. Scala et al. reported that 46–67% of BMS patients claim to experience xerostomia, regardless of whether salivary flow is reduced; notably, xerostomia is often subjective and not a true decline in salivary gland function²⁸. Studies have reported that treatment with clonazepam for the treatment of BMS can simultaneously alleviate xerostomia and reduce burning pain, suggesting the existence of similar neuropathological pathways²⁰. Perimenopausal women often experience concurrent xerostomia and oral burning²⁹. This evidence suggests a close relationship between xerostomia and the occurrence of burning pain. Our data revealed that there was no significant difference in the stimulated salivary flow rate between BMS patients with or without xerostomia; however, BMS patients with xerostomia had significantly reduced resting salivary flow rates, which is consistent with previous reports^30,31. Our findings further indicated that most BMS patients with dry mouth had mild to moderate dryness, and there was no significant correlation between the severity of oral dryness and salivary flow rates. The sensation of dry mouth is perceived by the peripheral nervous system and transmitted to the central nervous system, but the mechanism remains unclear¹². Xerostomia is correlated with salivary flow rates, as well as the wettability of the oral mucosa surface and changes in salivary composition³². This explains the discrepancy between subjective symptoms of dry mouth and objective indicators of salivary flow rates.

Saliva is essential for the maintenance of oral health. Saliva coats the oral soft tissues in the form of what is known as the mucosal pellicle, which has the functions of barrier, lubrication and immunomodulation^33,34. Xerostomia may increase the risk of mucosal abrasive injuries and candidiasis, leading to oral mucosal atrophy or erythema, which can subsequently induce localized nociceptive pain. BMS is a diagnosis of exclusion, characterized by the absence of organic lesions². Localized nociceptive pain caused by xerostomia may not be the primary pathological mechanism underlying BMS. In recent years, growing evidence suggests that BMS is associated with sensory dysfunction and represents a neuropathic pain disorder accompanied by central or peripheral nerve sensitization³⁵.

In this study, we evaluated pain perception (pain sensitivity) in patients with BMS in two dimensions: experimental pain thresholds and pain intensity scores. We selected the tip of the tongue, which is most commonly affected in BMS patients, as the site for measuring experimental pain thresholds. After confirming the accuracy and test–retest reliability of the electronic algometer, we used it to measure the PPT at this site. Unlike previous findings by Inamochi, there was no significant difference in the PPT between BMS patients with and without dry mouth¹⁴. The PPT reflects deep pain sensitivity, possibly mediated by C- and A-δ fibres, and is significantly and independently correlated with sex, anxiety level, and sleep quality^23,36. PPT differs across different regions of the oral mucosa, as well as between head and non-head regions³⁷. Differences in subjects, study sites, and peripheral neuropathological mechanisms may explain the discrepancies between our findings and those of previous reports. Xerostomia may not be a key factor affecting experimental pain thresholds in patients with BMS. It has been reported that pain intensity scores may have greater clinical relevance than experimental pain thresholds do, as suprathreshold stimulation may be more closely related to clinical situations³⁸. In this study, we used the PSQ instead of experimental pain intensity scores, which have been previously reported to have a good correlation. In our study, the BMS patients in the dry-mouth group had significantly higher PSQ-minor scores, indicating greater general pain sensitivity in the BMS patients with xerostomia.

Multiple regression analysis revealed that PSQ-minor scores in the dry-mouth group were not significantly correlated with salivary flow rates or the severity of dry mouth, but were significantly associated with the duration of dry mouth. The duration of dry mouth could explain 14.3% of the variation in pain sensitivity in BMS patients with dry mouth. The longer the duration of dry mouth was, the higher the PSQ-minor score was in the BMS patients. Our data revealed only a weak correlation between experimentally obtained PPTs and self-rated PSQ-minor scores, which is consistent with previous reports^17,36,39. Earlier reports have shown that self-reported PSQ-minor scores are positively correlated with increased grey matter volume in the parahippocampal gyrus³⁹. Long-term xerostomia may induce or exacerbate anxiety and depression in BMS patients, and the parahippocampal gyrus is involved in the modulatory effect of these negative emotions on pain^40,41. It is inferred that enhanced parahippocampal gyrus function may mediate the impact of dry mouth on self-rated pain sensitivity.

In clinical practice, individual disparities in pain perception are of significant concern. Since altered pain sensitivity serves as both a trait and a risk element for numerous pain disorders, understanding these differences is crucial⁴². BMS frequently coincides with temporo-mandibular disorder (TMD), fibromyalgia, or visceral pain³⁵. Prolonged xerostomia is correlated with heightened pain sensitivity in BMS. Hence, the early management of dry mouth is advantageous for enhancing the quality of life and may potentially lower the risk of other chronic pain complications. The measures for managing xerostomia encompass, among others, facilitating the application of oral moisturizing substances, curtailing the use of medications causing dryness as authorized by doctors, and implementing behavioral stress management strategies.

Our study is also limited by several issues. The study was cross-sectional, and it was not possible to establish a causal relationship between xerostomia and pain sensitivity in patients with BMS. In this study, pain intensity perception was not measured experimentally, but was rated on the basis of imagined situations. Further research is needed to determine whether the differences in PPT and PSQ-minor scores between BMS patients with and without dry mouth are due to differences in pain thresholds and pain intensity ratings or to differences between experimental and imagined pain stimuli. While our study rigorously excluded patients with visible mucosal damage or systemic conditions linked to xerostomia, it is important to acknowledge that unmeasured variations in salivary composition or subtle mucosal barrier dysfunction might contribute to pain in a subset of patients. This may have increased the risk of uncertainty within the study population. Future research incorporating alterations in salivary components among BMS patients with xerostomia could help further elucidate the pathophysiological mechanisms involved.

Conclusion

Xerostomia, commonly known as oral dryness, constitutes a frequently observed concomitant symptom among patients afflicted by BMS. In the course of our research endeavor, it was ascertained that xerostomia elicits disparate effects on two separate dimensions of pain sensitivity within the BMS patient cohort. Precisely, the mechanical pain threshold measured experimentally exhibited no connection with the presence of xerostomia. On the contrary, xerostomia was associated with an upsurge in the scores of self-assessed suprathreshold pain intensity. The findings of our study contribute to the enrichment of the current knowledge regarding somatosensory abnormalities in BMS patients. This, in consequence, has the capacity to promote a more profound exploration of the pathological processes underlying BMS.

Abbreviations

BMS

Burning mouth syndrome

D–W

Durbin–Watson statistic

HIS

The International Headache Society

PPT

Pressure pain threshold

PSQ

Pain sensitivity questionnaire

SD

Standard deviation

SE

Standard error

SWS

Stimulated whole saliva

SXI

Summated Xerostomia Inventory

USWS

Unstimulated whole saliva

VIF

Variance inflation factor

Author contributions

H.Z. designed and wrote the manuscript. S.R., W.H. analyzed the data. H.Z., K.G., W.L. collected clinical data. All the authors read and approved the manuscript.

Funding

No funding was obtained for this study.

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the local ethics committee, the Medical Research Ethics Committee of the First Affiliated Hospital of Zhengzhou University. The interviewer (before trained) gave the patients detailed information about the study, and the interview was carried out after receiving informed consent from the patients. Patients in this study had a detailed knowledge of the disease and agreed to participate in the investigation.

Consent for publication

Not applicable.