10.59987/ads/2010.1.14-18
Background and objective. Burning Mouth Syndrome (BMS) is a common disease but still a diagnostic and therapeutic challenge for clinicians. Despite many studies its nature remains obscure and controversial; nowadays there is no consensus about definition, diagnosis and classification. BMS is characterized clinically by burning sensations in the tongue or other oral sites, often without clinical and laboratory findings. According to the etiology, BMS cases should be subdivided into three subtypes: BMS by local factors (lfBMS), BMS by systemic factors (sfBMS) and neurological BMS (nBMS), the most frequent, in which the symptom is caused by central or peripheral neurological malfunctions affecting in particular the taste pathway. To establish the type of BMS, both anamnesis and clinical examination, including laboratory tests, are necessary; nBMS cases will be recognized by exclusion of any other type. In case of lfBMS or sfBMS, the treatment of the main pathology will be resolutive; in nBMS cases many Authors proposed different pharmacological trials without satisfactory results and the current opinion is that a multidisciplinary approach is required to keep the condition under control.
This pilot study aimed to investigate whether the biostimulative effect of Low Level Laser Therapy (LLLT) could enhance the symptoms of nBMS cases, improving patients’ quality of life. Study design/materials and methods. Among 160 patients affected by oral burning sensation attending to the Oral Pathology Complex Operative Unit of the Department of Stomatological Sciences of Sapienza University of Rome, 77 resulted affected by nBMS. Twenty-five of these patients, 16 females and 9 males, were randomly selected for low level laser applications. All the patients were irradiated with a double diode laser (Lumix 2 Prodent, Italy) emitting contemporarily at 650 nm and 910 nm, with a fluence of 0.53 J/cm² for 15 minutes twice a week for 4 weeks. The areas of irradiation were the sides of the tongue on the path of taste fibers. A NRS (numerical rating scale) evaluation of maximum and minimum pain was registered before and after the treatment. In each case to the total value of NRS rates registered before the treatment was deducted the total NRS rate registered after the treatment. The difference was estimated effective if over two points. The Kruskall-Wallis test revealed the significance of the study (p&lt;0.0001) and the Dunn’s Multiple Comparison test, applied to compare NRS rates before and after the treatment, showed that there is not a statistically relevant difference between min NRS ratings before and after treatment, while there are statistically significant differences between max NRS ratings (p&lt;0.05). Results. All the patients agreed the treatment confirming the general good compliance related to laser treatments. No side effects were registered and all the patients completed the therapy without interruption. Seventeen patients (68%) had relevant benefits from the treatment with valid reduction of NRS ratings. In 8 cases the differences of NRS rates were not relevant being under the limit of reliability established in study design. In no case there was a worsening of the symptoms.
Conclusions: According to the results of this pilot study it is reasonable to suppose that LLLT may play an important role in the management of nBMS cases, more investigations are needed to clarify, by a greater number of cases and a placebo control group, the real effectiveness of this innovative LLLT application.
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Annali di stomatologia
laser dentistry
The low level laser therapy in the management of neurological burning mouth syndrome. A pilot study
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The low level laser therapy in the management of neurological burning mouth syndrome. A pilot study
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    The low level laser therapy in the management
    of neurological burning mouth syndrome.
    A pilot study




                                                                                               i
                                                                                             al
                                                                                           on
    Umberto Romeo, DDS1                                        partment of Stomatological Sciences of Sapienza
    Alessandro Del Vecchio, DDS1                               University of Rome, 77 resulted affected by nBMS.
    Mauro Capocci, DDS1                                        Twenty-five of these patients, 16 females and 9
    Claudia Maggiore, MD, DDS2                                 males, were randomly selected for low level laser ap-
    Maurizio Ripari, MD, DDS1                                  plications. All the patients were irradiated with a dou-




                                                                                         zi
                                                               ble diode laser (Lumix 2 Prodent, Italy) emitting
    “Sapienza” University of Rome, Rome, Italy                 contemporarily at 650 nm and 910 nm, with a fluence
    1 Department of Oral Sciences, (A. Polimeni)               of 0.53 J/cm² for 15 minutes twice a week for 4 weeks.




                                                                   na
    University of L’Aquila, L’Aquila, Italy                    The areas of irradiation were the sides of the tongue
    2 School of Dentistry, Oral Surgery Unit (C. Maggiore)     on the path of taste fibers. A NRS (numerical rating
                                                               scale) evaluation of maximum and minimum pain
    Corresponding author:                                      was registered before and after the treatment. In each
    Prof. Umberto Romeo                                        case to the total value of NRS rates registered before




                                                                 er
    Department of Oral Science                                 the treatment was deducted the total NRS rate regis-
    Via Caserta, 6 - 00161 Rome, Italy                         tered after the treatment. The difference was esti-
    Ph. +39-06-4997                                            mated effective if over two points. The
                                                               Kruskall-Wallis test revealed the significance of the
    E-mail: umberto.romeo@uniroma1.it                        ntstudy (p<0.0001) and the Dunn’s Multiple Compari-
                                                               son test, applied to compare NRS rates before and
                                                               after the treatment, showed that there is not a statis-
                                                 iI
    Summary                                                    tically relevant difference between min NRS ratings
    The low level laser therapy in the management of           before and after treatment, while there are statisti-
    neurological burning mouth syndrome. A pilot study.        cally significant differences between max NRS rat-
                                                               ings (p<0.05).
                                    on

    Background and objective. Burning Mouth Syn-               Results. All the patients agreed the treatment con-
    drome (BMS) is a common disease but still a diag-          firming the general good compliance related to laser
    nostic and therapeutic challenge for clinicians.           treatments. No side effects were registered and all
    Despite many studies its nature remains obscure and        the patients completed the therapy without interrup-
                            i


    controversial; nowadays there is no consensus              tion. Seventeen patients (68%) had relevant benefits
                         iz



    about definition, diagnosis and classification. BMS        from the treatment with valid reduction of NRS rat-
    is characterized clinically by burning sensations in       ings. In 8 cases the differences of NRS rates were not
    the tongue or other oral sites, often without clinical     relevant being under the limit of reliability estab-
          Ed




    and laboratory findings. According to the etiology,        lished in study design. In no case there was a wors-
    BMS cases should be subdivided into three sub-             ening of the symptoms.
    types: BMS by local factors (lfBMS), BMS by sys-           Conclusions: According to the results of this pilot
    temic factors (sfBMS) and neurological BMS (nBMS),         study it is reasonable to suppose that LLLT may play
    the most frequent, in which the symptom is caused          an important role in the management of nBMS cases,
    by central or peripheral neurological malfunctions af-     more investigations are needed to clarify, by a
    fecting in particular the taste pathway. To establish      greater number of cases and a placebo control
IC




    the type of BMS, both anamnesis and clinical exam-         group, the real effectiveness of this innovative LLLT
    ination, including laboratory tests, are necessary;        application.
    nBMS cases will be recognized by exclusion of any
    other type. In case of lfBMS or sfBMS, the treatment
C




    of the main pathology will be resolutive; in nBMS          Key words: oral pain, BMS, LLLT, laser dentistry.
    cases many Authors proposed different pharmaco-
    logical trials without satisfactory results and the cur-
    rent opinion is that a multidisciplinary approach is       Objectives and background
©




    required to keep the condition under control.
    This pilot study aimed to investigate whether the          Burning Mouth Syndrome (BMS) is a common disease that
    biostimulative effect of Low Level Laser Therapy           represents a diagnostic and therapeutic challenge for cli-
    (LLLT) could enhance the symptoms of nBMS cases,           nicians. Despite many studies tried to investigate this par-
    improving patients’ quality of life.                       ticular disorder, its real nature remains still obscure and
    Study design/materials and methods. Among 160 pa-          controversial, and at this moment there is no consensus
    tients affected by oral burning sensation attending to     about even the diagnosis and the classification of BMS.
    the Oral Pathology Complex Operative Unit of the De-       A lot of terms are used to describe similar situations, such

    14                                                                            Annali di Stomatologia 2010; I (1): 14-18
    The low level laser therapy in the management of neurological burning mouth syndrome. A pilot study


    as glossodynia, glossopyrosis, stomatodynia, and oral dy-        dosages, benzodiazepines, tricyclic antidepressant or an-
    sestesia.                                                        ticonvulsants may be effective; in patients with nBMS, ho-
    Affected patients often present with multiple oral complaints,   wever it must be considered that a long period treatment
    including burning, xerostomia and taste alterations. The         with these drugs may induce a xerostomia worsening the
    prevalence of BMS is 1.8-19% in the general population           oral distress.




                                                                                                      i
    (1-4) and it is higher in middle-aged post-menopausal wo-        Topical capsaicin has been used in some trials (22); Fe-




                                                                                                    al
    men (Male:Female ratio = 1:7), while children are never          miano and coll. (23) registered an enhancement of oral pain
    affected. The anterior two third of the tongue is the most       in nBMS with α-lipoic acid, confirming the neurological in-
    frequently affected site, followed by hard palate, lips and      volvement of this kind of BMS.
    gums (5-9).                                                      The aim of this study is to verify whether the biostimula-




                                                                                                  on
    Many causes, local or systemic, can raise these particu-         tive effect of low level laser therapy (LLLT) may enhance
    lar oral sensations creating great problems in diagnosis         the symptoms of nBMS cases improving patients quality
    and treatment.                                                   of life.
    Many patients affected by this pathology present eviden-




                                                                                                zi
    ce of anxiety, depression and personality disorders, but it
    is unresolved if the pain led to the psychological disorder      Materials and methods
    or vice versa (10-14).
    As a first, BMS patients should be sub-divided into two ca-      The study was realized at the Department of Stomatolo-




                                                                         na
    tegories, the first including all the cases presenting clini-    gical Sciences of Sapienza University of Rome in the pe-
    cal mucosal signs; the second one including all those pa-        riod between January 2004 and April 2009.
    tients without mucosal affections. Seventy-five per cent of      In this period 160 patients affected by oral burnings at-
    BMS cases belong to this second category (15).                   tended to the Oral Pathology Complex Operative Unit. In




                                                                       er
    The symptoms vary from different entity of burning sen-          order to identify the exact kind of the oral burning, in each
    sation, to pain, dry mouth (xerostomia), unpleasant and          case a clinical examination was performed and a series
    altered taste sensation and itching (16). Symptoms involve       of laboratory tests was requested. The complete series of
    tongue, palate, lips, and gums often in relation with re-        laboratory tests requested is reported in Table 1. After this
    movable dentures. Patients awaken without pain and re-
    fer increasing symptoms through the day and into the eve-
    ning. Symptoms often decrease during meals and working
    activity. The onset is sudden and sometimes related to den-
                                                               nt    first screening, only 77 patients could be recognized as af-
                                                                     fected by nBMS (Tab. 2).
                                                                     Amongst these cases, 25 patients, 16 females and 9 ma-
                                                                     les, were randomly selected for low level laser applications.
                                                     iI
    tal procedures. Most patients suffer from the pathology for      In every case a written informed consent to LLLT was re-
    long time, ranging from months up to years. According to         quested and obtained.
    its etiology, BMS should be differenced into three subtypes:     All the patients were irradiated with a double Gallium Ar-
                                        on

    BMS by local factors (lfBMS), BMS by systemic factors            senide (GaAs) laser (Lumix 2 by Prodent, Italy). This de-
    (sfBMS) and idiopathic BMS (iBMS) (17); lfBMS is caused          vice emits contemporarily at two wavelengths, 650 nm and
    by various pathologies affecting oral mucosa, such as ero-       910nm, in the red and near infrared respectively. The bio-
    sive lichen planus, acute or chronic candidiasis, allergies,     stimulative trial was performed by a cycle of 15 minutes
    trauma, geographic tongue, trigeminal neuralgia and pa-          of irradiating time, repeated twice a week for 4 weeks. The
                               i


    rafunctions. The sfBMS occurs as oral sign of systemic con-      fluence (F) irradiated was 0.53 J/cm². According to the hy-
                            iz



    ditions such as Sjögren syndrome nutritional deficiencies        pothesis of peripheral nerve damage in nBMS cases, the
    (e.g.: iron and B complex), type II diabetes (formerly known     irradiation areas were the sides of the tongue on the ana-
    as no-insulin dependent), hormonal changes, as during me-        tomical path of taste fibers. A NRS evaluation of maximum
           Ed




    nopause (18), hypothyroidism (19), and drug induced xe-          and minimum pain was registered before the first appli-
    rostomia.                                                        cation and after the whole treatment.
    The iBMS differs from the two previous conditions by lack        In each case to the total value of NRS rates registered be-
    of local signs and being often associated with neurologi-        fore the treatment was deducted the total NRS rate regi-
    cal disturbances like anxiety, hypochondriasis and espe-         stered after the treatment. The difference was estimated
    cially depression, so many Authors consider the main psy-        effective if over two points.
    chological factors responsible for this situation. In iBMS sa-
IC




    livary flow rates seems to keep into normal values as de-
    monstrated by Zhao et al (20). Recent studies about iBMS         Results
    have pointed to dysfunction of several cranial nerves as-
    sociated with taste sensation (16) or reduction of density       All the patients completed the treatment confirming the ge-
C




    of epithelial nerve fibers (21), as possible causes of the pa-   neral excellent compliance of laser treatments. The results
    thology, for this reason it should be reasonable to call this    obtained are reported in Table 3; in 17 cases (68%, 10 fe-
    particular form neurological BMS (nBMS) (Fig. 1).                males and 7 males) a clear reduction of total NRS rates
    Nowadays the diagnostic approach to BMS patients is still        was registered (total difference over 2 points). In remai-
©




    very difficult and needs a wide knowledge of the various         ning 8 cases (32%, 6 females and 2 males) the results were
    aspects of this pathology. In order to establish what kind       under the limit of efficacy established in study design (to-
    of BMS is affecting the patient, both anamnesis and cli-         tal difference between 0 and 2 points) and were considered
    nical examination, including laboratory tests are necessary.     ineffective. In no case a worsening of symptoms was re-
    In case of lfBMS or sfBMS the treatment of local or sy-          gistered. The Kruskall-Wallis test revealed the significance
    stemic pathology will be resolutive.                             of the study (p<0.0001) and the Dunn’s Multiple Compa-
    In nBMS patients a multidisciplinary approach has been           rison test, applied to compare NRS rates before and af-
    proposed to keep the condition under better control. In low      ter the treatment, showed that there is not a statistically

    Annali di Stomatologia 2010; I (1): 14-18                                                                               15
    U. Romeo et al.



     a                                                                 c




                                                                                                        i
                                                                                                      al
                                                                                                    on
                                                                                                  zi
                                                                      Figure 1a, b, c - Clinical normal appearance of a nBMS patient.
     b




                                                                          na
                                                                      Rochkind and coll. (25) that tested in rats the efficacy of
                                                                      780 nm laser phototherapy versus non irradiated controls
                                                                      on the acceleration of axonal growth and the nerve re-




                                                                        er
                                                                      generation after peripheral nerve reconstruction by poly-
                                                                      glicolic acid neurotube. The study demonstrated that the
                                                                      nerves were morphologically reconstructed in both groups,
                                                                      but the Sciatic Functional Index and the total number of
                                                                nt    myelinated axons were higher in laser treated group. Ih-
                                                                      san and co. (26) in 2007 in rabbits, showed the efficacy
                                                                      of 901 nm low level irradiation versus control, in regene-
                                                                      rative processes after surgical induced peroneal nerve sec-
                                                         iI
                                                                      tions. The evaluation was registered in the short and mid-
                                                                      dle period after surgery. Compared to the control groups,
                                                                      thicker nerve fibers, more regular myelin layers and
                                       on

    relevant difference between min NRS ratings before and            clearer Ranvier nodes were observed in treated group.
    after treatment, while there are statistically significant dif-   The differences between two groups were yet relevant in
    ferences between max NRS ratings (p<0.05)                         a short period, 2 weeks after surgery, and highly signifi-
                                                                      cant in mid period, 6 and 8 weeks, after surgery. Oron and
                                                                      coll. (27) investigated in vitro whether low level diode la-
                              i


    Discussion                                                        ser irradiation could enhance the ATP production in cul-
                           iz



                                                                      tured normal human neural progenitor (NHNP). The results
    The effectiveness of low level laser irradiation in peripheral    showed an almost double ATP production in irradiated cells
    nerve regeneration was demonstrated in several studies            versus non lased controls (7513 ± 970 units vs. 3808 ± 539
           Ed




    (24) both in vitro and in animal trials. One of the most in-      units), supporting the hypothesis of a good effectiveness
    teresting results in this research pathway was obtained by        of low level laser irradiation in human neuronal cells too.
                                                                      A peripheral nerve dysfunction, especially of taste pathway,


    Table 1 - Laboratory tests for clinical screening.
IC
C
©




    16                                                                                    Annali di Stomatologia 2010; I (1): 14-18
    The low level laser therapy in the management of neurological burning mouth syndrome. A pilot study


                                                                     Table 2 - Diagnosis after clinical and laboratory screening.




                                                                                                      i
                                                                                                    al
                                                                                                  on
                                                                                                zi
    Figure 2 - Low level laser irradiation of tongue.




                                                                         na
    in the aetiology of nBMS is long lasting, since Fox first ob-
    servations in 1931 (28). Many studies related the lack of        According with these observations we designed this pilot
    function of taste in predisposed subjects, the so-called su-     study to investigate whether neurological biostimulative ef-
    pertasters, with the burnings typical of the syndrome (29,       fects of LLLT could enhance oral nBMS patients’ complaints




                                                                       er
    30). The reliability of this hypothesis was showed as a first    by a reduction of symptoms. For this first observation the
    by histological study by Suarez and coll. (21) that showed       site of irradiation was arbitrarily established in the tongue
    in tongue biopsies a relevant lower density of epithelial ner-   sides, according to the anatomic distribution of taste fibers
    ve fibres in BMS patients versus controls. Similarly Lau-        (Fig. 2), independently from the referred sites of symptoms.
    ria and coll. (31) demonstrated that BMS patients tongue,
    compared to normal ones, shows a reduction of trigemi-
    nal small fibres.
                                                               nt    The obtained results of 68% effectiveness are encoura-
                                                                     ging together with no worsening cases and good patients’
                                                                     compliance. The study was also statistically significant by
                                                        iI
    Table 3 - Minimum and maximum NRS rates registered before and after LLLT.
                               i         on
                            iz
            Ed
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C
©




    Annali di Stomatologia 2010; I (1): 14-18                                                                                17
    U. Romeo et al.


    Kruskall-Wallis test (p<0,0001); the comparative Dunn’s            12. Grushka M, Epstein JB Gorski M. Burning mouth syndrome
    test showed significant results for Max NRS rates diffe-               and other oral sensory disorders: a unifying hypothesis. Pain
    rences (p<0,005) between pre and post treatment eva-                   Res Manag. 2003; 8(3): 133-5.
                                                                       13. Maina G, Albert U, Gandolfo S, Vitalucci A, Bogetto F. Per-
    luation, while min NRS rates differences were not signi-
                                                                           sonality disorders in patients with Burning mouth syndrome.
    ficant. This difference could be explained with the difficulty         J Pers Disord. 2005; 19(1): 84-93.




                                                                                                           i
    to establish clearly an exact value of minimum pain level,         14. Popper F. Psychogenic aspects of the Burning mouth. J Dent




                                                                                                         al
    while it is easier for a patient to be accurate in establishing        Assoc S Afr. 1968; 23(10): 357-8.
    the maximum pain evaluation rate.                                  15. Pindborg JJ. Atlas of diseases of the oral mucosa. Mun-
                                                                           ksgaard ed (COPENHAGEN) 1992; 238.
                                                                       16. Eliav E, Kamran B, Schaham R, Czerninski R, Gracely R,




                                                                                                       on
    Conclusion                                                             Benoliel R. Evidence of chorda tympani disfunction in patients
                                                                           with Burning mouth syndrome JADA; 2007; 138(5): 628-33.
                                                                       17. Balasubramaniam R, Klasser GD, Delcanho R. Separating
    This is only the first step of a research pathway that pre-            oral burning from burning mouth syndrome: unravelling a dia-
    views further investigations, in order to clarify the other que-       gnostic enigma. Aust Dent J 2009; 54; 293-99.




                                                                                                     zi
    stions still unresolved at the moment. As a first a higher         18. Del Vecchio A, Podda G, Rossi L, Francalanci P. Burning
    number of cases are mandatory to obtain statistically si-              Mouth Syndrome: indagine immunoistochimica sulla presenza
    gnificant results and versus control study is necessary to             nelle mucose orali di recettori specifici per gli estrogeni. In




                                                                           na
    avoid placebo effects. At last, it could be necessary to ap-           Atti II Simposio SIOG Padova 1992; 255.
    ply multiple system of pain evaluation to prevent subjec-          19. Femiano F, Lanza A, Bonaiuto C, Gombos F, Nunziata M,
                                                                           Cuccurullo L, Cirillo N. Burning mouth syndrome and Bur-
    tive bias in records.
                                                                           ning mouth in hypothyroidism: proposal for a diagnostic and
    According to this pilot experience it is reasonable to pre-            therapeutic protocol. Oral Surg Oral Med Oral Pathol Oral
    sume that LLLT biostimulative effects may play an effec-               Radiol Endod. 2008; Jan 105(1): e22-7.




                                                                         er
    tive role in the management of nBMS cases, however fur-            20. Zhao M, Chen Q, Lin M. Relationship between the symptom
    ther studies are needed to establish whether it can be cle-            of xerostomia and non-stimulated salivary flow rates in pa-
    arly considered the resolution of this long lasting clinical           tients with burning mouth syndrome. Hua Xi Kou Qiang Yi
    dilemma.                                                               Xue Za Zhi. 2001; 19(3); 169



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©




    18                                                                                      Annali di Stomatologia 2010; I (1): 14-18
