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Burning mouth syndrome is a debilitating condition of chronic oral pain and/or burning, which mainly affects pre and postmenopausal women. It can be characterized by the presence of other symptoms, such as a sensation of dry mouth (xerostomia), a bitter or metallic taste (dysgeusia) and tingling. BMS can be classified into two clinical forms: primary and secondary BMS. The primary BMS is essential or idiopathic, in which the organic local/systemic causes cannot be identified.
The secondary BMS is caused by local, systemic, and/ or psychological factors; thus, its diagnosis depends on identification of the exact causative factor. Its etiology is complex and not well defined, suggesting neuropathic mechanisms.
Its diagnosis continues to be a challenge for the clinician since there are no sufficiently objective and universally accepted criteria. This disease is usually characterized by presenting many symptoms, but without clinical signs, which makes its diagnosis difficult as it excludes lesions in the oral mucosa by its own definition.
Therapy has been found to be effective for reducing the oral burning or pain symptom in some BMS patients previous clinical trials found that drug therapy with capsaicin, alpha-lipoic acid, clonazepam, and antidepressants may provide relief of oral burning or pain symptom but given the complexity of this syndrome, there are currently no widely accepted guidelines for its treatment.
Aim :Update knowledge on burning mouth syndrome treatment, pathophysiology, analyzing current and innovative therapeutic procedures and assessing their effective efficacy.
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1971-1441
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en
R. Gatto
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Annali di stomatologia
burning tongue
Burning mouth syndrome: a literary review and an uptade 
Text.Serial.Journal
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Original Article
2023-03-03
2023-03-03
2021-12-01
2023-12-04
2-5
Ann Stomatol (Roma)
R. Gatto
2021
10.59987/ads/2021.1-4.2-5
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Pediatric Dentistry, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy  (pediatric dentistry)
1971-1441
1-4
burning tongue
en
5
Burning mouth syndrome: a literary review and an uptade 
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                                                                                                     Original article


Burning mouth syndrome:
a literary review and an uptade


Matteo Mazzuka1                                             Keywords: Burning mouth syndrome, xerostomia,
Gianluca Botticelli2*                                       dysgeusia, glossodynia; oral pain; burning tongue.
Enrico Ivagnes1
Antonino Spagnolo1                                          Introduction
Sara Caruso2
Roberto Gatto2                                              Definition Burning mouth syndrome (BMS) is an enigmatic,
                                                            idiopathic, chronic and often painful clinical form for which
1
  Private practice                                          no validated and standardized definitions, diagnostic crite-
2
  Pediatric Dentistry, Department of Life, Health and En-   ria or classifications have yet been established. It was first
  vironmental Sciences, University of L’Aquila, 67100       described by Fox in 1935 (1). The American Academy of
  L’Aquila, Italy (pediatric dentistry)                     Orofacial Pain defines BMS as a burning sensation in the
* Corresponding Author                                      oral mucosa despite the absence of clinical findings and
                                                            abnormalities in laboratory tests or imaging (2,3).
                                                            The International Association for the Study of Pain
Corresponding author:                                       (IASP) defines BMS as a burning pain of the tongue
Roberto Gatto                                               or other oral mucosal membrane associated with nor-
                                                            mal signs and laboratory findings lasting at least 4 to 6
                                                            months. The current version of the World Health Organ-
                                                            ization International Classification of Diseases uses the
                                                            term glossodynia, which includes additional terms such
Abstract                                                    as glossopyrosis and painful tongue, and describes the
Burning mouth syndrome is a debilitating condition of       condition as painful sensations in the tongue, including
chronic oral pain and/or burning, which mainly affects      burning sensations (2,4 ).
pre and postmenopausal women. It can be character-           The epidemiology of BMS is difficult and imprecise since
ized by the presence of other symptoms, such as a           there are no universally accepted definitions, the differ-
sensation of dry mouth (xerostomia), a bitter or metallic   ent epidemiological studies often refer to different clinical
taste (dysgeusia) and tingling. BMS can be classified       entities in which there are no lesions of the oral mucosa.
into two clinical forms: primary and secondary BMS.         Therefore, the prevalence varies greatly from one study
The primary BMS is essential or idiopathic, in which the    to another, probably in relation to the diagnostic criteria.
organic local/systemic causes cannot be identified.         The prevalence of glossodynia in the general population
The secondary BMS is caused by local, systemic, and/        is estimated at 2.5 to 5.1% (5). In a study by Bergdahl
or psychological factors; thus, its diagnosis depends       and Bergdahl (6), the prevalence was estimated at 3.7%
on identification of the exact causative factor.            of 1,427 subjects aged between 20 and 69 years ,espe-
Its etiology is complex and not well defined, suggest-      cially postmenopausal women (7).
ing neuropathic mechanisms. Its diagnosis continues
to be a challenge for the clinician since there are no
sufficiently objective and universally accepted criteria.
                                                            Etiology
This disease is usually characterized by presenting         Primary BMS is essential or idiopathic, in which the
many symptoms, but without clinical signs, which            causes cannot be identified, and it is probable that there
makes its diagnosis difficult as it excludes lesions in     is a neuropathological cause that manifests itself with
the oral mucosa by its own definition.                      sensory alterations (hypoesthesia), is due to the reduc-
Therapy has been found to be effective for reducing         tion of the nociceptive trigger threshold, or due to neuro-
the oral burning or pain symptom in some BMS pa-            physiological where there are no defined findings.
tients previous clinical trials found that drug thera-      Secondary BMS is caused by systemic,local and psy-
py with capsaicin, alpha-lipoic acid, clonazepam, and       chological nature factors like, anemia, vitamin B defi-
antidepressants may provide relief of oral burning or       ciency, folic acid and zinc, diabetes, thyroid disease,
pain symptom but given the complexity of this syn-          drugs such as angiotensin-converting enzyme inhibitors
drome, there are currently no widely accepted guide-        and hypoglycemic agents, irritations, parafunctional hab-
lines for its treatment.                                    its and oral infections. At the immunological level, there
Aim :Update knowledge on burning mouth syndrome             could be those of allergic origin, such as the hypersen-
treatment, pathophysiology, analyzing current and in-       sitivity reaction to dental materials. In fact, it is possible
novative therapeutic procedures and assessing their         that allergies may play a role in the development of burn-
effective efficacy.                                         ing mouth syndrome (2,8).

Annali di Stomatologia 2021; XII (1-4): 2-5                                                                                  2
    Burning mouth syndrome: a literary review and an uptade

    Among the psychological factors that predispose to suf-        interdisciplinary approach for the proper management
    fering from BMS are psychiatric disorders of anxiety and       of these patients. Although many drugs have been pro-
    severe depression. In fact, in one study Suresh et al.         posed, none of them prove to be a number one stand-
    Identified anxiety and depression as the most common           ard. Treatment planning must be personalized for each
    disorders presented by patients with BMS (9).                  patient. If local, systemic, or psychological factors are
                                                                   evident, treatment or elimination should be attempted
                                                                   (17). A complete clinical examination of the oral muco-
    Pathophysiology                                                sa is crucial in these patients to define a treatment. The
                                                                   lack of pathology of the oral mucosa is mandatory for
    Patients with BMS usually show a series of typical symp-       the diagnosis of BMS. Details related to quality, onset,
    toms of alteration of the trigeminal nerve: altered percep-    persistence, intensity, onset, duration, relieving factors,
    tion of pain, alteration of neural transmission, increased     course, sites involved in pain symptoms are essential.
    excitability and finally, a negative affectation of the
    trigeminal-vascular system, which shows the presence
    of a multifactorial component (10).
                                                                   Non-pharmacological treatment
    Recent studies such as those by Feller et al. 2017 (11),
    Silvestre et al. 2015 (12), and Coculescu et al. 2015 (13),    The initial treatment will be non-pharmacological, trying
    where neurophysiological, psychophysical and neu-              to treat those medical processes that can give rise to
    ropathological factors are included, have clarified that       discomfort or burning in the mouth, managing all those
    several neuropathic mechanisms, mostly subclinical, act        irritative situations that can give rise to small traumas
    at different levels and contribute to the pathophysiology      on the tongue or lips, such as fractures or very promi-
    of primary BMS. Demonstration of loss of small-diame-          nent dental cusps, as well as as areas of hyperpressure
    ter nerve fibers in the epithelium of the tongue with an       of the prosthesis on the mucous membranes. The pa-
    upregulation of the TRPV1 and P2X3 receptor accounts           tient should be informed about her situation, avoiding all
    for the thermal hypoesthesia and increased taste detec-        doubts that could increase her level of anxiety. Mucous
    tion thresholds seen on quantitative sensory testing. As       protectors can be used, which protect against friction,
    in neuropathic pain, decreased brain activation to heat        rubbing and thermal changes (2,14,15).
    stimuli has been shown in patients with primary BMS.
                                                                   Pharmacological treatment
                                                                   The use of Capsaicin is an alternative that has been
    Diagnosis
                                                                   used to control neuropathic pain. It is based on the de-
    The clinical diagnosis is fundamentally based on the dis-      sensitization of thermal, chemical and mechanical stim-
    comfort reported by the patient, also taking into account      uli by acting on C fiber receptors. It is used as a gel or
    that the typical profile will be that of an older woman, be-   mouthwash with which a certain degree of improvement
    tween the 5th and 7th decades of life, accompanied by a        can be obtained, but with a limited effect over time (2) .
    significant anxious component (14,15). In the oral exam-       The use of topical Clonazepam has had very good short-
    ination, it is necessary to rule out the presence of lesions   term results, being effective in 2/3 of patients. This drug
    that demonstrate the existence of some local or systemic       acts by inhibiting pain transmission and suppressing
    process that can explain the appearance of symptoms.           central neuronal hyperactivity in cases of deafferenta-
    Parafunctional habits and alterations secondary to them        tion. In patients resistant to clonazepam, Gabapentin
    can only be seen occasionally.                                 can be used, but its results are contradictory (2). Other
    According to the studies by Zakrzewska et al. (2016) and       types of treatments used have been Amilsupride, Parox-
    Sun et al. (2013) the criteria to be taken into account when   etin and Sertraline. At low concentrations it has an anal-
    diagnosing a patient with BMS are based on (15,16) pres-       gesic action, but the studies carried out do not provide a
    ence of symptoms including daily deep burning sensation        sufficient level of efficacy and evidence.
    of the oral mucosa (bilateral),pain for at least 4-6 months,   In traditional medicine, the first-line treatment of choice
    with variable intensity during the day that do not interfere   for BMS generally consists of selective serotonin reup-
    with sleep.                                                    take inhibitors (SSRIs) or serotonin and norepinephrine
                                                                   reuptake inhibitors (SNRIs). As an alternative treatment,
                                                                   the traditional Japanese medicine (kampo) Rikkosan
    Treatment                                                      was also used. Rikkosan consists of five raw herbs
                                                                   (Asiasarum root (saishin), Cimicifuga rhizome (shoma),
    There are several therapeutic methods that are used            Saposhnikovia root (boufu), Glycyrrhiza (kanzou), and
    in BMS. From a clinical perspective, clinicians should         Japanese Gentian (ryutan)) and are indicated as natural
    initially determine signs and symptoms consistent with         pain relievers (18).They observed Rikkosan mouthrinse
    primary (essential/idiopathic) BMS or with secondary           produces pain relief lasting approximately 1 hour.
    BMS in which symptoms are caused by underlying local           The treatment of BMS requires an interdisciplinary ap-
    or systemic conditions. Secondary BMS requires proper          proach for the proper management of these patients. In
    diagnosis and treatment of such conditions.                    this regard, low-level laser therapy (LLLT) has been con-
    In primary BMS, the cause is unclear, so management            sidered as an alternative for the treatment of SBA due
    options are based on the patient’s symptoms, often             to its analgesic and regenerative action on peripheral
    leading to unsatisfactory results (16). The complex and        nerve fibers. The results of the studies are highly satis-
    multifactorial etiology of BMS requires a systematic and       factory and show a significant improvement in symptoms

3                                                                                      Annali di Stomatologia 2021; XII (1-4): 2-5
M. Mazzuka et al.

after treatment. According to Ana Liz Pereira de Matothe        satisfactory response or remission rate and stabilize ef-
best energy dosage should be between 0.5 and 8 J /              ficacy (22).
cm 2 because it can reduce inflammation and accelerate          According to Daniel L. Neuman the use of variable dos-
wound healing. LLLT has an analgesic effect; however,           age naltrexone up to 4.4 mg has been shown to relieve
the application it must be successive, continuous and in        symptoms after 8 weeks, the patient reported a reduc-
several sessions                                                tion of at least 50% in the severity of subjective pain as-
The therapy that the low-level laser has is described           sociated with the symptoms of burning mouth syndrome
minimal side effect and has a reduction in symptoms in          and the improvements remained consistent during the
BMS (19).                                                       follow-up visits at 11 months, with no need for modifica-
Alpha-lipoic acid (ALA), which is an antioxidant that can       tion. the dosage (23).
scavenge free radicals and exert nerve repair activity,
has also been studied. Clinical trials have investigated        Psychological treatment
the efficacy of this substance in the treatment of BMS,
but the results are conflicting (19).                           Likewise, Komiyama et al. (24) have investigated the
According to Wenqing Zhang photobiomodulation (PBM)             effectiveness of group cognitive behavioral treatment
can help relieve pain, speed up the resolution of inflam-       to improve pain and anxiety in patients with BMS. They
mation process and promote healing of damaged tissues.          designed a brief group CBT intervention to provide dis-
By stimulating mitochondrial cytochromes and then ini-          ease self-management skills and introduce behavioral
tiating secondary cell signaling pathways. Studies have         strategies to manage chronic and persistent BMS pain.
shown that PBM was effective in many parts of the body,         Pain intensity and disturbance in daily life decreased sig-
such as for the treatment of musculoskeletal injuries, de-      nificantly from the first to the second CBT session. The
generative diseases and dysfunctions.A single treatment         state anxiety score also decreased after the CBT ses-
is generally sufficient for acute and postoperative ther-       sion and approached the control value. They report that
apy. However, up to 10 treatments may be needed for             individual and group cognitive therapy has been shown
chronic pain and degenerative diseases presenting min-          to be equally effective in managing chronic pain, since
imal side effects with improvements over clonazepam             there were no significant differences between the two.
in reducing pain sensation over the 12-week follow-up           But according to the patients’ narrative impressions, the
period (21).                                                    CBT group intervention may be more useful to control
According to daniela adamo et all. Vortioxetina is well         persistent pain in patients with BMS, since it provides
tolerated and effective in the treatment of BMS, suggest-       mutual psychological support. Therefore, they conclude
ing a new frontier in the management of this disease and        that a brief cognitive-behavioral intervention group is ef-
other chronic pain conditions by offering good safety           fective in reducing pain and anxiety in patients with BMS.
and tolerability, with lower latency of action, especially in   Likewise, the reduction of anxiety can also be useful to
middle-aged or elderly patients. with medical comorbidi-        reduce the intensity of pain in these patients. Although
ties, also offering improved cognitive function. Treatment      studies of the effect of duration of CBT therapies on
should be performed for at least 12 months to achieve           burning sensation complaints are needed.




Annali di Stomatologia 2021; XII (1-4): 2-5                                                                                   4
    Burning mouth syndrome: a literary review and an uptade

    Conclusion and perspective                                        7.    Dahiya, P., Kamal, R., Kumar, M., Niti, Gupta, R., & Chaud-
                                                                            hary, K. Burning mouth syndrome and menopause. Inter-
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    Therefore, since there is not a single drug capable of                  tal materials in patients with lichenoid oral mucosal lesions
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    were more useful. in reducing burning in the mouth.                     R, Lemmer J. Burning Mouth Syndrome: Aetiopathogenesis
                                                                            and Principles of Management. Pain Research and Man-
    The topical and systemic use of clonazepam has been
                                                                            agement. 2017; Article ID 1926269, 6 pages. https://doi.
    found to be advantageous, with the precaution of tak-                   org/10.1155/2017/1926269
    ing individual measures with the chronic diseases they            12.   Silvestre FJ, Silvestre-Rangil J, López-Jornet P. Síndrome
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                                                                      13.   Coculescu EC, Manole G, Coculescu BI, Purcărea VL.
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    and anxiety, reducing pain intensity and should always            15.   Zakrzewska J, Buchanan JA. Burning mouth syndrome.
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                                                                            nal of Oral Pathology & Medicine. 2013;42(9):649–55. doi:
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                                                                      17.   Wardrop RW, Hailes J, Burger H, Reade PC. Oral discom-
    In the future, with the proper use of diagnostic tests, pa-             fort at menopause. Oral Surg Oral Med Oral Pathol 1989;
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                                                                            burning mouth syndrome. Traditional & Kampo Medicine.
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    to encourage the scientific community to continue with            19.   Daniela Adamo,Giuseppe Pecoraro,Noemi Coppola,Elena
    this line of research, which will benefit both the experts              Calabria1,Massimo Aria,Michele Mignogna .Vortioxetine
    and the patients who suffer from this syndrome.                         versus other antidepressants in the treatment of burning
                                                                            mouth syndrome: An open-label randomized trial.Oral Dis .
                                                                            2021 May;27(4):1022-1041. doi: 10.1111/odi.13602.
                                                                      20.   Barbosa NG, et al. Evaluation of laser therapy and alpha
                                                                            - lipoic acid for the treatment of burning mouth syndrome:
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