Burning Mouth Syndrome: Review of Current and Emerging Therapeutic Strategies

Abstract

Background/Objectives: Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder characterized by persistent intraoral burning in the absence of detectable mucosal alterations. Diagnosis is challenging due to the lack of specific biomarkers and the need to exclude numerous systemic and local conditions that can mimic oral burning. This literature review aims to summarize current and emerging therapeutic strategies for BMS. Methods: A structured and filtered search of PubMed, Scopus, and Web of Science identified studies evaluating pharmacological, phytotherapeutic, and non-pharmacological interventions. Results: Various antidepressants, anticonvulsants, benzodiazepines, H2 receptor antagonists, and low-dose naltrexone have demonstrated varying degrees of symptom reduction, while alpha lipoic acid (ALA) and phytomedicines such as capsaicin, Hypericum perforatum, Catuama, lycopene, crocin, and melatonin show mixed clinical benefits. Non-pharmacological approaches, including photobiomodulation (PBM), oral cryotherapy, neuromodulation techniques, and cognitive behavioral therapy, also provide meaningful symptom improvement in many patients. Conclusions: Across all modalities, therapeutic responses remain heterogeneous and generally incomplete, underscoring the absence of a universally effective treatment. Current evidence supports an individualized and multidisciplinary approach that integrates pharmacological, psychological, and adjunctive therapies to address the multifactorial nature of BMS.

1. Introduction

Chronic idiopathic orofacial pain (COFP) comprises a heterogeneous group of disorders characterized by diverse clinical features, including spontaneous, continuous, or intermittent pain, often described as stabbing and/or burning, and commonly associated with sensory alterations [1].

Burning mouth syndrome is a COFP because a clearly recognizable cause is not possible to identify [2]. This chronic condition is characterized by a burning sensation in the oral cavity or dysesthesia without any detectable alteration of the oral mucosa. It is often associated with dysgeusia and xerostomia [3]. It affects a small percentage of the general population, with a higher prevalence in women, especially in postmenopausal age [4].

Burning mouth syndrome remains only partially understood, and although it was once considered a psychogenic disorder, it is now regarded as a multifactorial condition, with growing evidence supporting a neuropathic origin [5]. Burning Mouth Syndrome may arise from peripheral small-fiber neuropathy involving increased Transient Receptor Potential cation channel subfamily V member 1 (TRPV1) expression in the oral mucosa, from subclinical trigeminal neuropathy indicated by abnormal masseter and blink reflexes (~20% of patients) [6], or from centrally mediated pain linked to dopaminergic hypofunction resembling that seen in Parkinson’s disease [6]. Neurophysiological and imaging findings further implicate dysfunction of the nigrostriatal dopaminergic system, also associated with affective disorders; psychological and physical symptoms may reflect a shared central dysfunction [7,8]. Anxiety and depression appear frequently in BMS patients, as supported by systematic and STAI-based assessments [9,10]. Additional alterations include reduced plasma adrenaline levels [11] and variable evidence of neuroinflammatory involvement, with some studies reporting elevated IL-6 or TNF-α in affected individuals [12,13].

Patients with BMS commonly report a persistent burning sensation, usually bilateral, affecting the anterior two-thirds of the tongue and sometimes extending to the palate, gingiva, oral mucosa, and, in about 10% of cases, the lower lip; symptoms may include allodynia, sharp or electric-shock pain, tingling, numbness, and itching, often worsened by spicy or acidic foods [14]. A second type of burning mouth syndrome is a secondary syndrome (SOB), characterized by local or systemic alterations that can explain the symptoms [15].

Several etiological classifications have been proposed, including the distinction between primary and secondary BMS [3], the identification of three clinical subtypes based on symptom patterns and psychiatric involvement [16], and categorizations of potential causes into local, systemic, psychological, neurological, and idiopathic categories [17]. Systemic factors associated with secondary BMS include autoimmune disorders, nutritional deficiencies, such as iron, zinc, vitamin B12, and folates; endocrine and metabolic disorders, including diabetes, thyroid disease, and anemia; as well as the use of medications such as benzodiazepines, neuroleptics, and antihypertensives [15,18].

Zinc deficiency has been implicated, as supplementation has been shown to significantly reduce pain scores compared with controls [19]. Thyroid dysfunction, particularly hypothyroidism, as well as abnormalities in TSH, anti-TPO, anti-TG, and FT3 levels, has been associated with BMS and is frequently accompanied by taste disturbances. Local contributing factors include inadequate denture fit, parafunctional habits, oral galvanism, allergic reactions, oral mucosal abnormalities (candidiasis, lichen planus) and xerostomia [20,21]. Diagnosis is primarily based on the exclusion of secondary causes through detailed history taking, comprehensive clinical examination, and appropriate laboratory investigations, complemented by psychometric assessment and evaluation for gastroesophageal reflux [14]. The diagnosis of secondary BMS is established after a careful evaluation of the patient’s clinical and pharmacological history, physical examination, and laboratory findings [22]. Management is primarily directed at the underlying causes, often leading to symptom remission [23], and frequently requires a multidisciplinary approach involving dentists, physicians, nutritionists, and other specialists [5].

Burning mouth syndrome is associated with several clinical challenges. Diagnosis is often difficult, as it is based on exclusion and lacks specific clinical signs or biomarkers; all potential local and systemic causes of oral burning must therefore be ruled out before BMS can be confirmed [22]. This diagnostic process is often lengthy and may lead to misdiagnosis or delayed diagnosis, particularly because of overlap with other conditions such as oral candidiasis, thyroid disorders, and gastrointestinal diseases [5]. In addition, responses to available treatments are often inconsistent, and spontaneous remission seems to be rare, with reported rates of approximately 3–4% after 5–6 years from diagnosis [24].

Currently, no universally accepted guidelines exist for the treatment of BMS, and available review articles mainly report clinical studies with short follow-up periods (<2 months) [25]. The significant impact of BMS on patients’ quality of life and stomatognathic function highlights the need for further investigation into its underlying causes, with the aim of improving diagnostic accuracy and expanding therapeutic options [5].

The aim of this study is to provide a comprehensive overview of the therapeutic approaches currently available for the management of BMS, including both established interventions and emerging treatment modalities.

2. Materials and Methods

This narrative and comprehensive review includes a structured search strategy and protocol to select the most relevant items from the literature, ensuring the information provided is reliable and trustworthy. The search strategy used the PubMed, Web of Science, and Scopus databases. The search strategy was conducted using the following search terms: “Burning Mouth Syndrome” “BMS” “Stomatodynia” “Oral Pain” “Neuropathic Pain” “Oral Cavity” “BMS” “Diagnosis” “Treatment”. The chosen articles were arranged in a structured document that included the authors’ names, publication year, type of study, and the key information and conclusions presented. Therefore, the collected data were organized in “Management of Patients Affected by BMS”, which was further structured into “Pharmacological therapy”, “Oral Cryotherapy”, “Saliva substitutes”, “Alpha-lipoic acid (ALA)”, “Phytomedicine”, “Photobiomodulation (PBM)”, and “Neuromodulation and physiological techniques against BMS”.

2.1. Eligibility Criteria

Studies were included if they met the following criteria: (1) studies published in the English language; (2) studies addressing therapeutic approaches for BMS; and (3) Clinical studies (randomized and non-randomized trials), observational studies, systematic and narrative reviews, case series, and case reports. Studies were excluded if they met one or more of the following criteria: (1) studies not published in the English language; (2) conference proceedings and abstracts; and (3) studies not addressing the therapeutic management of BMS.

2.2. Study Selection

To conduct this narrative review, the authors followed the SANRA (Scale for the quality Assessment of Narrative Review Articles) guidelines [26]. Two independent authors (P.B. and R.P.) carried out the primary literature search and then conducted a subsequent evaluation of the selected articles, excluding studies that did not meet the predefined eligibility and inclusion criteria. The full texts of the eligible studies were then reviewed to determine their suitability for final inclusion. Disagreements between the reviewers were resolved through discussion and re-evaluation. The most recent search was conducted on 16 October 2025. The retrieved records were downloaded and imported into Zotero (Corporation for Digital Scholarship, Vienna, VA, USA), where the screening process was subsequently conducted.

3. Management of Patients Affected by BMS

The initial approach to managing patients affected by BMS focuses on ruling out underlying systemic or local conditions through a thorough clinical evaluation and laboratory testing [27]. Symptom alleviation and enhancement of quality of life are achieved using traditional pharmacological approaches, including anticonvulsants (such as gabapentin and pregabalin) and antidepressants (such as amitriptyline and nortriptyline) [24]. Medicinal plants and natural supplements, such as alpha-lipoic acid (ALA) and phytotherapeutics, have demonstrated modest benefit in pain reduction for some patients [25]. A multidisciplinary approach that combines medical treatment with psychological therapy, including cognitive behavioral therapy, is recommended to address both pain and associated psychological comorbidities [28].

3.1. Pharmacological Therapy

3.1.1. Antidepressants

Selective Serotonin Re-uptake Inhibitors (SSRIs) inhibit the re-uptake of serotonin, prolonging its availability at the synaptic cleft [29]. The study of Adamo et al. reported that sertraline, paroxetine, and vortioxetine were all associated with sustained symptom improvement in the long-term. However, a clear reduction in vortioxetine’s therapeutic response was observed at the six-month evaluation [30].

Serotonin–norepinephrine re-uptake Inhibitors (SNRIs) act on both noradrenergic and serotonergic neurons in the nervous system. Serotonin and norepinephrine mediate the endogenous mechanisms of pain inhibition [31]. Among these, milnacipran has demonstrated significant efficacy in reducing chronic orofacial pain [32]. This effect appears to be dose-dependent, as Kato et al. [33] reported progressively higher improvement rates with daily doses of 30, 60, and 90 mg. Trazodone is a second-generation antidepressant with serotonergic activity and has been used in the treatment of anxiety and pain symptoms. A regimen of 100 mg/day for the first four days followed by 200 mg/day for eight weeks did not result in significant pain reduction compared with placebo [24]. Moreover, its clinical use is limited by frequent adverse effects, including dizziness, drowsiness, abdominal discomfort, headache, palpitations, tremor, xerostomia, and urinary incontinence [34].

Amitriptyline, a tricyclic antidepressant, is commonly used for its analgesic properties. In a recent retrospective study comparing amitriptyline and clonazepam, both treatments were associated with pain reduction at six weeks and three months. The main issue with Amitriptyline is its frequent side effect of xerostomia, which can worsen the pre-existing dry mouth associated with BMS [35].

3.1.2. Anticonvulsants

Gabapentin and Pregabalin reduce the release of excitatory neurotransmitters such as glutamate, noradrenaline, and substance P by binding to the α2δ subunit of voltage-gated calcium channels. Because of their favorable hepatic safety profile, these drugs are commonly used to manage pain associated with diabetic neuropathy and post-herpetic neuralgia [36].

In a crossover study, patients with BMS were treated with Gabapentin, ALA, a combination of both, or a placebo. Fifty percent of the patients receiving Gabapentin reported improvement in pain scores, compared with only 15% in the placebo group. The combination of the anticonvulsant with ALA produced superior effects, with a 70% reduction in patient pain [25]. Similar findings were already reported in a previous study, in which administration of 300 mg of Gabapentin combined with ALA resulted in significant pain improvement and, in some cases, complete recovery after two months of treatment [37].

Topical gabapentin is administered as an oral rinse preparation (commonly 250 mg/mL) and targets local neuropathic pain by inhibiting voltage-gated calcium channels and reducing excitatory neurotransmitter release [38]. A retrospective study reported that topical gabapentin led to a median 2-point reduction in burning pain scores on a 0–10 numeric rating scale over a median follow-up of 86 days, with mild adverse reactions (15.8%), such as transient oral discomfort, and no serious safety concerns [38]. Systematic reviews also support modest efficacy of gabapentin, particularly in combination with ALA [25].

The study of Adamo et al. [39] evaluated the effect of pregabalin at a dose of 150 mg/day on pain reduction in patients with treatment-resistant BMS. After four months of therapy, patients who were non-responders to initial SSRI or SNRI treatment and received pregabalin augmentation reported a significant reduction in visual analog scale (VAS) scores, indicating relevant clinical improvement in oral burning symptoms. Pregabalin was generally well tolerated, with a low rate of adverse events, supporting its use as an adjunctive option in refractory cases of BMS [39]. In addition, systemic use of Pregabalin (150 mg), compared to Clonazepam (2 mg), showed significant efficacy in reducing pain scores, although it was associated with the risk of more severe potential side effects [40].

Clonazepam topical administration seems to be a suitable option for the initial management of BMS. It provides rapid pain relief, although short duration, and reduces the side effects associated with oral administration [41]. In the study of Rodríguez de Rivera Campillo et al. [42], Clonazepam (0.5–2.0 mg) significantly reduced pain intensity compared with placebo after just one month of treatment. At six months, most patients treated with this benzodiazepine showed a 50% reduction in symptoms, with five experiencing total remission. Furthermore, a meta-analysis by Cui et al. [43] confirmed that topical Clonazepam is an effective treatment modality for both short-term (less than ten weeks) and long-term (more than ten weeks) use. However, mood, taste dysfunction, and xerostomia did not show clear improvement, and side effects such as dizziness, transient diarrhea, and myalgia have been reported [44].

3.1.3. H2 Receptor Antagonists

Lafutidine is an H2 receptor antagonist that inhibits gastric acid secretion [45]. A randomized controlled study involving 71 patients with BMS demonstrated the benefits of administering 10 mg of Lafutidine twice daily. In the group treated with the drug, the improvement in VAS scores compared to baseline was significant after four, eight, and twelve weeks of treatment. Minor side effects, including mild nausea and abdominal distension, did not require treatment discontinuation [46]. However, evidence supporting the use of H2 receptor antagonists in BMS remains limited.

3.1.4. Low Dose Naltrexone

Low-dose naltrexone (LDN), usually administered at 3–4.5 mg daily, acts as a partial opioid receptor antagonist and has anti-inflammatory and immunomodulatory effects, potentially modulating central and peripheral pain pathways. Case reports and small clinical studies suggest that LDN may reduce pain intensity by up to 50% in refractory BMS, with additional benefits for comorbid pain conditions and minimal side effects [47,48]. Nevertheless, high-quality randomized controlled trials are still lacking, and its use remains off-label.

3.2. Oral Cryotherapy

Oral cryotherapy involves the application of cold stimuli to the oral mucosa, typically using ice chips or cold water rinses, aiming to reduce local nerve conduction and inflammation. Its mechanism is hypothesized to decrease peripheral nerve activity and modulate pain signaling [49]. In a recent multi-institutional randomized controlled trial, oral cryotherapy, especially when combined with photobiomodulation (PBM), demonstrated significant pain reduction and improvement in anxiety symptoms in patients with burning mouth syndrome, with a high overall response rate and no severe adverse events reported, indicating a favorable safety profile [49].

3.3. Saliva Substitutes

Saliva substitutes, such as lysozyme–lactoperoxidase and urea, often relieve xerostomia in patients with burning mouth syndrome, which can further affect taste function [50,51]. Mouth rinses with lysozyme–lactoperoxidase did not show a reduction in pain compared to placebo in the long term (four months) [50]. Topical application of urea also did not show a statistically significant difference compared to placebo after three months [51].

3.4. Alpha Lipoic Acid (ALA)

Alpha lipoic acid is a powerful universal antioxidant used in treating diabetic neuropathies [52] and has been investigated in randomized controlled trials (RCTs) for the management of BMS. In a double-blind placebo-controlled trial on 60 patients, daily administration of 600 mg of ALA resulted in symptomatic improvement in 64% of treated individuals, with most of these patients maintaining some benefit one month after therapy. A reduction in symptoms was also observed in a portion of placebo-treated subjects [53]. In another randomized study comparing ALA and low-level laser therapy (LLLT) in both BMS and secondary oral burning (SOB), ALA increased unstimulated salivary flow in BMS and contributed to symptom relief in both conditions [54].

3.5. Phytomedicine

3.5.1. Capsaicin

Capsaicin, derived from Capsicum frutescens, is a potent agonist of the TRPV1 (transient receptor potential vanilloid) receptor, a non-selective cation channel predominantly expressed in sensory neurons. Initially, its application causes a transient burning sensation due to the binding of capsaicin to TRPV1, which opens the channel, allowing the influx of Na+ and Ca++ ions and subsequent membrane depolarization [55]. For this reason, pre-treatment with anesthetic cream has been proposed to reduce the temporary increase in intraoral burning sensation caused by capsaicin patches [56]. This initial burning sensation is followed by a longer phase of analgesia, during which pain fibers become less sensitive to nociceptive stimuli due to functional and structural changes in the nerve fibers; this may explain the long-lasting pain relief associated with capsaicin, and supports its possible role in chronic pain conditions such as BMS [57]. Previous studies have shown that these receptors are increased in the lingual mucosa of patients with BMS. Activation of TRPV1 in the peripheral nerve endings triggers the release of neuropeptides such as substance P, neurokinin A (NKA), and calcitonin gene-related peptide (CGRP), which may contribute to pain through hyperalgesia and inflammation [7,58]. Short-term studies (two months) on capsaicin have reported symptom improvement in 76% of participants, with a significant reduction in VAS scores; in long-term studies (four months), topical capsaicin also maintained a significant reduction in VAS scores, suggesting sustained efficacy in managing symptoms over time [50]. The oral administration of capsaicin appears to improve VAS scores in patients with BMS, although its use is limited by the possibility of adverse effects such as gastric pain [59].

3.5.2. Hypericum Perforatum

The active extracts derived from Hypericum perforatum have a strong affinity for gamma-aminobutyric acid (GABA), adenosine, serotonin 5HT1 receptors, and benzodiazepine receptors. Additionally, they act as a monoamine oxidase inhibitor (MAOI), contributing to antidepressant and anxiolytic effects [60]. By inhibiting the re-uptake of norepinephrine, serotonin, and dopamine, Hypericum perforatum may provide antidepressant effects [60]. As a GABA agonist, it induces temporary hyperpolarization of the neuronal membrane, leading to desensitization and inhibition of neurotransmission, and therefore, anxiolytic and analgesic effects [61]. Ślebioda et al. [62] systematically reviewed randomized controlled trials on BMS and concluded that Hypericum perforatum did not produce a significant reduction in pain compared with placebo. Moreover, Hypericum perforatum is generally well-tolerated, and it rarely causes adverse reactions, except for dizziness. However, when used in combination with other medications, it may lead to severe interactions. By activating cytochrome P450 enzymes, which are involved in drug metabolism, it reduces the plasma concentration and potency of certain drugs, such as warfarin, cyclosporine, oral contraceptives, anticonvulsants, digoxin, theophylline, and HIV protease inhibitors. Additionally, it may increase the serotonergic action of serotonin receptor agonists (triptans), SSRIs, SNRIs, TCAs, and MAOIs [63].

3.5.3. Catuama

Catuama is an herbal product composed of four medicinal plant extracts: Paullinia cupana (guarana), Trichilia catigua (catuaba), Zingiber officinale (ginger), and Ptychopetalum olacoides (muirapuama). It acts on dopaminergic, serotonergic, and opioid pathways, demonstrating antidepressant, antinociceptive, and vasorelaxant effects in animal models [64]. Catuama has shown a significant reduction in pain scores in patients with BMS after three months compared to the placebo group. Mild side effects reported include drowsiness, weight gain, and insomnia [65].

3.5.4. Lycopene

Lycopene is a carotenoid found in fruits and vegetables, particularly in tomatoes. It has antioxidant, anti-inflammatory, and anti-apoptotic properties [66,67]. In a double-blind study on 60 patients with BMS, the effect of administering olive oil enriched with lycopene (300 ppm) was compared to a placebo (water and coloring) over 12 weeks. Both groups showed improvement in VAS scores, but without statistically significant differences [68].

3.5.5. Crocin

Crocin is a carotenoid found in flowers of the Crocus genus; it has neuroprotective effects by reducing oxidative stress and cell death by inhibiting microglial activation and suppressing inflammatory cytokine production [69,70]. It was demonstrated that Crocin is a source of antioxidant activity against reactive oxygen species (ROS) [71]. Palmitoylethanolamide (PEA) is an endogenous compound (fatty acids and ethanolamide) with anti-inflammatory and analgesic properties belonging to the N-acyl ethanolamines. Its micronized (mPEA) or ultra-micronized (umPEA) forms have shown a progressive reduction in pain intensity, statistically more significant than the control, in patients suffering from chronic and/or neuropathic pain [72]. Its efficacy has also been studied in patients with BMS. After administering 1200 mg/day of umPEA, a significant short-term benefit (60 days) was observed, although this effect diminished after four months [73].

3.5.6. Melatonin

Melatonin is a neurohormone that regulates circadian biological rhythms and possesses antioxidant, anti-inflammatory, anticancer, anxiolytic, and antinociceptive activities [74]. A crossover clinical study of Varoni et al. [75] using high doses of melatonin, thus 12 mg/day, did not provide pain relief or improvement in sleep scores compared to placebo in the short term (two months). Four patients discontinued the treatment due to side effects such as severe tremors, sexual dysfunction, blurred vision, and a severe sensation of heaviness. Castillo-Felipe et al. [76] reported that the administration of significantly lower doses of melatonin (1 mg/day) reduces the burning sensation, depression, and anxiety without the occurrence of serious side effects.

3.6. Photobiomodulation (PBM)

Photobiomodulation uses various light sources to modulate cellular and tissue responses, supporting wound healing and providing antimicrobial effects. It has analgesic, anti-inflammatory, and biological stimulation effects, improving pain relief and tissue healing [77].

Low-level laser therapy is a modality within PBM that employs lasers with power typically below 500 mW, using either red or infrared wavelengths, and has demonstrated efficacy in reducing pain and improving oral health-related quality of life in BMS [78]. In addition, it reduces the burning sensation by increasing the release of serotonin and β-endorphins while decreasing bradykinin secretion. It blocks the depolarization of C fibers, which transmit heat and pain stimuli [79]. Reduced burning may also occur due to the decrease in vasodilation caused by the narrowing of the capillary diameter [80].

A long-term study suggested the advantage of PBM in orofacial neuropathic pain, including BMS, with a 4.5-fold likelihood of pain reduction compared to placebo. However, no improvement was observed in the patients’ psychological well-being or quality of life [81]. Other studies have also highlighted the efficacy of PBM, such as the one conducted by Arbabi-Kalati et al. [82], who evaluated 20 patients with BMS divided into two groups (laser and placebo). The laser group received irradiation (gallium-arsenide-iodine laser, 630 nm, 30 mW, 1 J/cm²) twice weekly for two weeks, targeting 10 sites of the oral mucosa, while the placebo group received the same treatment with the laser turned off. At the end of the two-week treatment, the laser group showed a statistically significant improvement in VAS scores compared with placebo.

Given its effects on pain reduction and quality of life, PBM may represent an alternative option for BMS. Photobiomodulation has been reported to be superior to Clonazepam in providing consistent and long-lasting pain relief [83]. However, further evidence is needed to confirm its efficacy and safety. In addition, treatment parameters (wavelength, power, dose, exposure time, spot size) and application techniques still require optimization.

3.7. Neuromodulation and Physiological Techniques Against BMS

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique proposed for BMS after brain neuroimaging studies reported changes in the pain matrix [84]. Unilateral rTMS of the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) produced widespread analgesic effects in both experimental and clinical pain studies [85]. Umezaki et al. [86] reported a rapid decrease in VAS scores, which remained stable for up to two months following rTMS treatment. However, this approach requires expensive equipment and considerably more time and commitment in the clinic than conventional pharmacological treatments.

Cognitive Behavioral Therapy (CBT) is used to manage depression, anxiety, and physical symptoms. Techniques include biofeedback, relaxation, exposure, and cognitive reframing. In BMS, pain-related catastrophizing affects both the intensity of pain and the quality of life and may sustain chronic symptoms. Interventions aimed at reducing pain-related catastrophizing have significantly improved symptoms in patients with BMS [87].

Cognitive behavioral therapy demonstrates favorable efficacy in the management of BMS, with evidence supporting both short- and long-term symptom improvement. A systematic review of randomized controlled trials reported that CBT, along with topical capsaicin, clonazepam, and laser therapy, was associated with significant reductions in pain scores and improved coping with chronic oral discomfort in BMS patients. The review highlights that psychological interventions such as CBT are among the few non-pharmacological approaches with sustained benefit, particularly in patients with comorbid anxiety or depression, and recommends further high-quality studies to establish standardized protocols for psychological support in BMS treatment [24].

3.8. Limitations and Future Perspectives

This study has limitations. First, due to its narrative design, the evidence is synthesized descriptively, which limits the generalizability of the findings and precludes the formulation of definitive clinical recommendations. Second, a structured comparison between treatments was not conducted, as differences in study design, sample size, follow-up, and outcome measures limit direct comparability across interventions. Finally, the current evidence appears insufficient to clearly establish links between underlying pathophysiological mechanisms and treatment selection in BMS, which limits the ability to develop targeted, mechanism-based therapeutic strategies [88].

Future research on BMS should prioritize large and randomized controlled trials with standardized outcome measures. Emerging therapies, including LDN, oral cryotherapy, and rTMS, require further validation in controlled studies. Salivary biomarker development is a promising frontier, with salivary metabolomics revealing shifts in tyrosine metabolism that may reflect impaired dopaminergic transmission, and meta-analytic data identifying elevated salivary cortisol and α-amylase as potential diagnostic biomarkers [89,90]. Personalized treatment strategies should be guided by mechanistic subtyping-tailoring therapy to the underlying etiopathogenetic mechanism and individualizing it to patient-specific contributing factors.

4. Conclusions

Burning Mouth Syndrome remains a complex condition with unclear etiology, challenging diagnosis, and highly variable therapeutic outcomes. Available pharmacological options, including antidepressants, anticonvulsants, benzodiazepines, H2 receptor antagonists, and selected phytotherapeutics, may provide partial symptom relief, while PBM, oral cryotherapy, neuromodulation techniques, and CBT represent promising adjuncts. However, no single intervention offers a consistent long-term resolution. The current evidence indicates that effective management requires a personalized and multidisciplinary strategy that addresses neuropathic, psychological, hormonal, and local contributing factors. Further well-designed studies with standardized protocols and longer follow-up are needed to establish optimal treatment approaches and improve clinical outcomes.