The use of self‐report questionnaires in an analysis of the multidimensional aspects of pain and a correlation with the psychological profile and quality of life in patients with burning mouth syndrome: A case‐control study

Abstract Background The symptomatology in Burning Mouth Syndrome (BMS) is complex and it should be considered in accordance with a biopsychosocial model. Objectives To evaluate the multidimensional aspects of pain with a complete battery of tests and to analyse its relationship with potential predictors such as mood disorders, sleep and quality of life. Methods Forty patients with BMS versus an equal number of age and sex‐matched healthy controls were enrolled. The VAS, SF‐MPQ, BPI, PD‐Q, BDI‐II, STAI, PSQI, ESS, SF‐36 and OHIP‐14 were administered. Results The scores of the VAS, SF‐MPQ, BPI, PD‐Q, BDI‐II, STAI, PSQI, SF‐36 and OHIP‐14 were statistically significantly higher in the BMS patients than the controls (p < .001**). A strongly linear correlation between pain (VAS, SF‐MPQ, BPI and PD‐Q) and disease onset (STAI, BDI‐II, PSQI and sub‐items of SF‐36 and OHIP‐14) was found. In the multiple regression analysis, the contributions of the BDI‐II and OHIP‐14 were found to be statistically significant with the SF‐MPQ, PD‐Q and BPI in terms of severity and interference, while the contributions of the STAI and sleep were found to be statistically significant with the SF‐MPQ and BPI in terms of severity and interference, respectively. Conclusions Pain tests are differently correlated with mood and quality of life. Therefore, a complete analysis of the patient requires several tools to better understand the multidimensional aspects of pain in BMS.


| INTRODUC TI ON
Burning Mouth Syndrome (BMS) is a complex chronic oro-facial pain disorder characterised by pain in the oral cavity without any evident clinically causative lesions. In accordance with the International Classification of Oro-facial Pain, 1st edition (ICOP 2020), 1 BMS is defined as an intra-oral burning or dysaesthetic sensation, recurring daily for more than 2 h per day for more than 3 months, without evident causative lesions on clinical examination and investigation; including patients report not only bilateral intra-oral or facial pain but also those with a unilateral symptomatology. The aetiology is unknown and is probably of multifactorial origin, with increasing evidence that BMS may be a neuropathic disorder involving the central and peripheral nervous system. 2 The worldwide prevalence of the disease is around 4% but varies considerably in relation to the different definitions of BMS with consequent different inclusion criteria considered. The prevalence increases in post-menopausal women (18%), with a female-to-male ratio ranging from 3:1 to 20:1. 3 This is probably due to a reduction in the sexual hormones, which can cause a toxic effect on the peripheral and central neurons.
The main symptom reported by patients affected by BMS is pain. 4 This is, therefore, the primary element to consider in any BMS diagnosis. The pain is usually persistent, of moderate intensity and poorly localised and described as dull, pressing or of a burning character, either scalding, tingling or numbing. It does not disturb sleep and is less severe in the morning, getting worse during the day, although generally alleviated by eating and drinking. The most common site for the pain or burning is the tongue (the anterior two-thirds or the tip), followed by the hard palate, gingivae, lower lips and pharynx. The symptomatology is frequently complicated by additional symptoms such as dysgeusia, subjective xerostomia, a bitter/metallic taste, sialorrhea, globus and foreign body sensation. 3 Pain manifested in the physical and anatomical dimensions is characterised by psychological, social and cultural dimensions that affect the subjective experience of pain in a biopsychosocial context. The complete analysis of the symptoms of BMS and of the way in which they can affect the life of the patient is very complex and continues to be a challenge for clinicians. For this reason, various questionnaires have been used in the assessment of pain in patients with BMS in order to evaluate every feature of this multidimensional symptomatology. 3 Traditionally, the Visual Analogue Scale (VAS), 5,6 the Numeric Rating Scale (NRS) 7 and the short form of the McGill Pain Q uestionnaire (SF-MPQ ) [8][9][10] have been the most frequently used tools for measuring and estimating pain intensity and quality in BMS. In addition, recently, in three studies [11][12][13] the Pain DETECT Questionnaire (PD-Q) has been used in a screening stage to evaluate the neuropathic component of pain in this disease. However, none of these questionnaires are able to assess how the pain interferes with the patient's functioning. In contrast, the Brief Pain Inventory (BPI) 14 is a simple and valid tool able to measure not only the intensity and location of the pain but also the degree of interference in the lives of patients with either nociceptive or neuropathic pain. Accordingly, it has been used only in our previous study and in the study of Lee et al. 15 Until now, few studies have investigated the pain experience of patients affected by BMS through a comprehensive pain assessment including several questionnaires, taking into account also the psychological profile of the patients and analysing the potential predictors of pain. [16][17][18] Therefore, the primary outcome of this study has been to investigate the intensity, quality and interference of the pain through the use of different questionnaires such as the VAS, SF-MPQ, PD-Q and BPI in order to obtain a comprehensive multidimensional analysis. The secondary outcome has been to evaluate the relation between pain, mood disorders (anxiety, depression and sleep disorders) and quality of life (QoL) to better understand, which are the most important predictors that may affect the experience of pain.

| Study design and participants
This was an observational case-control study, which was con- The target sample size equal to 40 patients for each group (BMSs and controls) was set by fixing a power test value (1-Beta) no less than 99% associated with a significance of no more than 1%. This sample size was carried out using the effect size value of 1.49, measured in a previously published research study regarding the PSQI scale. 20 The calculations were computed using Gpower software (v 3.1.9).
At the beginning 90 participants were recruited, aged 55-75 years. They included patients from our group suffering from BMS at the first consultation who had never been treated and, in addition, healthy subjects presenting for routine dental treatment during the study period. Every eligible subject was invited to participate in this study and provided written informed consent. No payment was provided for participation. The patients with BMS and the controls were enrolled in order to match the sample by age, gender and educational level. At the baseline appointment (time 0), 46 patients in the study group and 44 in the control group were considered eligible for this study. At the end of this process, considering the target sample size, 40 individuals in each group met the inclusion and exclusion criteria.
In accordance with the International Classification of Oro-facial Pain (ICOP 2020) 1st edition, 1 the inclusion criteria of the BMS group were: • patients experiencing an intra-oral burning or dysaesthetic sensation, recurring daily for more than 2 h per day for more than 3 months, without evident causative lesions on clinical examination and investigation; the pain has the characteristics of burning quality and is experienced superficially in the oral mucosa; • patients, male or female, aged at least 18; • patients with normal blood test findings (including blood count, blood glucose levels, glycated haemoglobin, serum iron, ferritin and transferrin); • patients who are not currently in treatment with psychotropic drugs.
The BMS group exclusion criteria were: • patients suffering from diseases that could be recognised as a causative factor of BMS; • patients unable to understand or complete the questionnaires; • patients having a history of a psychiatric disorder or a neurological or organic brain disorder; • patients undergoing treatment with psychotropic drugs or systemic drugs possibly associated with oral symptoms; • patients having a history of alcohol or substance abuse; • patients suffering from obstructive sleep apnoea syndrome (OSAS).
The inclusion criteria of the healthy subjects were: • subjects without any lesion of the oral mucosa; • subjects referring to the dental clinic for routine dental care without acute/chronic pain; • subjects, male or female, aged at least 18; • subjects without a psychiatric disorder or a neurological or organic brain disorder; • subjects without a history of BMS; • subjects with normal blood test findings (including blood count, blood glucose levels, glycated haemoglobin, serum iron, ferritin and transferrin); • subjects who had not undergone treatment with psychotropic drugs.
The exclusion criteria of the healthy subjects were: • subjects unable to understand or complete the questionnaires; • subjects having a history of alcohol or substance abuse; • subjects suffering from OSAS.

| Measures
At their first consultation, all the participants underwent a careful medical analysis, specifically an intra-and extra-oral examination by an expert clinician in oral medicine (DA). Their gender, age, years of education, family situation, job status, disease onset (in years), sleep duration (in hours), risk factors (current smoking status, alcohol consumption), oral symptoms and their location, medical comorbidities and systemic drugs taken were recorded and their Body Mass Index (BMI) was calculated.
In addition, the patients and controls underwent the following battery scales for a complete analysis of any pain experienced and their psychological profile and QoL ( Figure 1).

| Pain assessment
The Visual Analogue Scale (VAS) 21 is a validated instrument used to measure the intensity of pain. Patients mark a 10 cm scale ranging from the absence of pain (at the 0 cm end) to maximum pain (at the 10 cm end); the distance between 0 and the patient's mark indicates the intensity of the pain suffered.
The short form of the McGill Pain Questionnaire (SF-MPQ) 22 is a measure of the quality of pain. It is a multidimensional pain questionnaire, which measures the sensory, affective and evaluative aspects of the perceived pain. 23 It comprises 15 items from the original MPQ, each scored from 0 (none) to 3 (severe). There are no established critical cut-off points for the interpretation of the scores and, as for the MPQ, a higher score indicates worse pain.
The Pain DETECT Questionnaire (PD-Q) 11 is a reliable screening tool with a high sensitivity and specificity for the identification of neuropathic pain. 24 It is a self-reported questionnaire useful to classify pain into three groups: neuropathic, unclear or nonneuropathic pain. It consists of nine items: seven descriptive items describe the patient's sensorial experience rated on a scale from 0 to 5 (never, hardly, slightly, moderately, strongly and very strongly noticed), one item for the pain radiating pattern (0 to 2 points), and one item for the pain temporal pattern (−1 to 1 point). For diagnostic purposes, a validated algorithm was used to calculate a total score ranging from 0 to 38. A score of less than 12 indicates the presence of nociceptive pain, a score of 12-19 is suggestive of possible neuropathic pain while a score of over 19 confirms certain neuropathic pain. 11 The Brief Pain Inventory (BPI) 14 is a validated and widely used inventory that has been developed to assess the severity of pain and the interference of pain. 25 It is a 9-item self-administered questionnaire in which the pain severity is assessed by 4 items, including the worst and least severe pain experienced in the previous 24 h, the pain severity on average and the pain 'right now', ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The pain-related interference assesses the degree to which the pain affects the 7 domains of functioning (general activity, mood, walking ability, normal work, relations with other people, sleep and the enjoyment of life).

| Depression
The Beck's Depression Inventory (BDI-II) 26 is a self-administered test used, in clinical practice and research, to assess depression. It is composed of 21 items, each scored from 0 to 3, with higher scores indicating higher levels of depression.

Domain
Test Abbreviation Description E valuation S core Pain Visual Analogue Scale VAS U nidimensional measure of pain intensity. Score is determined by measuring the distance on the line between the "no pain" and the patient's mark, providing a range of scores from 0-10.

Self 1 minute
Total score: 0-10 T o assess the impact that oral health problems can have on an individual's quality of life; it consists of 14 items that explore seven domains of impact (functional limitation, pain, psychological discomfort, physical disability, psychological disability, social disability and handicap). All items are presented with a fivecategory rating scale ranging from "never" (0), "hardly ever" (1), "occasionally" (2), "often" (3), to "very often" (4).   where the respondent has the worst possible health, to 100, where the respondent is in the best possible health.

| Oral health-related quality of life
The OHIP-14 32 is a questionnaire composed of 14-items used to evaluate the consequences of oral diseases in seven dimensions: functional limitations, social handicap, disability, physical disability, psychological disability, discomfort and pain.

| Statistical analysis
The

| RE SULTS
The socio-demographic characteristics, the prevalence of systemic diseases and the drug consumption of the sample are shown in .029*). In addition, no statistically significant differences were found in relation to the prevalence of systemic diseases and drug consumption between the cases and controls.
Comparisons of the clinical parameters between the BMS patients and controls are summarised in The type and location of the oral symptoms are shown in Table 3.
Statistically significant differences were found between the cases and controls in relation to most of the symptoms. All the BMS patients reported a burning sensation followed by xerostomia ( 35%) or after a stressful life event (12; 30%).

p-Value
Age (in years) −0.06 (0.14) .690 −0.06 (0.14) .669 −0.07 (0.14) .602 −0.02 (0.14) .859 −0.02 (0.14) .    The present study provides a wide evaluation of the pain experience and psychological profile in a sample of patients with BMS analysing the intensity, quality, severity and interference of pain on daily life activities and evaluating all the predictors that contribute to the pain experience.

Multiple linear regression model predicting PD-Q Predictors
In this study, pain was described by all the patients as burning in quality and it was considered the worst symptom by 23 (57%). Therefore, a comprehensive evaluation using not only unidimen- Moreover, considering that QoL was the second most important domain according to the IMPACCT recommendations, clinicians should consider the SF-36 and OHIP-14 as additional tools to complete the analysis. 47 It is difficult to select a unique questionnaire among these used because, despite the fact that in this study the OHIP-14 was the tool more closely correlated with several components of the pain, it is also appropriate to consider the SF-36 as a more complete questionnaire, effective in evaluating every component of the QoL.
Regarding the evaluation of the psychological profile, the choice of using self-administration tools, such as the BDI-II, STAI, PSQI and ESS, seems to be adequate in the assessment of anxiety, depression and sleep disturbance in BMS. 7 Indeed, these questionnaires are simple to use and have demonstrated a good correlation with pain.
In particular, as suggested by our results, it must be emphasised that depression was the most important predictor of pain and, therefore, it should be taken into account that a high level of depression may in-

| CON CLUS IONS
The results of the current study show that patients with BMS suffer a high level of pain and that this type of pain, in terms of intensity and quality, seriously interferes with the individual's life activities.
Mood disorders, sleep quality and QoL are differently correlated with the pain questionnaires and these factors may contribute to the pain experience. However, the significance of the role of the psychological constructs on the pain experience remains unclear.
In particular, depression could play a critical role in the pain experience of BMS patients. Conversely, demographic and risk factors, BMI, disease onset and sleep duration did not correlate with pain.
The complexity of the symptomatology in BMS patients dictates the need to evaluate the intensity of pain using not only unidimensional tools, such as the VAS, but also multidimensional questionnaires, such as the SF-MPQ and BPI, in order to better understand the quality and interference of pain. In addition, self-administration questionnaires, such as the BDI-II, STAI, PSQI, ESS, SF-36 and OHIP-14 should be considered for a comprehensive assessment of the psychological profile and QoL in patients affected by BMS.

ACK N OWLED G EM ENTS
Open access funding provided by Universita degli Studi di Napoli Federico II within the CRUI-CARE Agreement.

AUTH O R S CO NTR I B UTI O N S
FC and DA conceptualised the study, EC defined the methodology; FC and EC performed the data collection; LDA and MA performed the statistical analysis; GP, GM and PS participated in conceptualisation of the study and participated in manuscript editing. FC, EC and DA drafted the manuscript; MDM, DA and GP participated in defining the methodology and in manuscript editing; MDM and DA contributing to the scope of discussion. All authors approved the final version of the manuscript.

CO N FLI C T O F I NTE R E S T
The authors have no conflict of interest, no financial support and no off-label or investigational use to declare.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data are available on request from the authors-The data that support the findings of this study are available from the corresponding author upon reasonable request.