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Published in: The Journal of Headache and Pain 1/2017

Open Access 01-12-2017 | Research article

Refractory burning mouth syndrome: clinical and paraclinical evaluation, comorbidities, treatment and outcome

Authors: Dimos D. Mitsikostas, Srdjan Ljubisavljevic, Christina I. Deligianni

Published in: The Journal of Headache and Pain | Issue 1/2017

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Abstract

Background

Burning Mouth Syndrome (BMS) is a chronic pain condition characterized by persistent intraoral burning without related objective findings and unknown etiology that affects elderly females mostly. There is no satisfactory treatment for BMS. We aimed to observe the long-term efficacy of high velanfaxine doses combined with systemic and topical administered clonazepam in a particular subgroup of BMS patients who do not respond to current clinical management.

Results

Eight (66.1 ± 6.2 years old females) out of 14 BMS patients fulfilled the inclusion criteria and were treated with venlafaxine (300 mg/d) and clonazepam (5 mg/d) for 35.4 ± 12.1 (mean ± SD) months. The average duration of the symptoms at baseline was 4.3 ± 1.4 years and the overall mean daily pain intensity score was 8.6 ± 1.3 (VAS); pain was in tongue and within the oral mucosa, accompanying by oral and facial dysesthesia. In five patients tasting was abnormal. All patients had positive history of concomitant primary headache. The average score of Hamilton Rating scale for Anxiety and Depression was 21 ± 4.2, and 26.1 ± 2.9, respectively. Previous ineffective treatments include anticonvulsants and anti-depressants. All patients responded (more than 50% decrease in VAS) after three months treatment (mean VAS 3.2 ± 2.2) with no remarkable adverse events.

Conclusion

BMS deserves bottomless psychiatric evaluation and management when current available treatments fail. Treatment with venlafaxine combined with topical and systemic clonazepam may be effective in refractory BMS cases but further investigation in a large-scale controlled study is needed to confirm these results.
Literature
1.
go back to reference Headache Classification Committee of the International Headache Society (IHS). International Classification of Headache Disorders, 3rd edition. Cephalalgia 2013;33:629-808. Headache Classification Committee of the International Headache Society (IHS). International Classification of Headache Disorders, 3rd edition. Cephalalgia 2013;33:629-808.
2.
go back to reference Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MD (2014) A population-based study of the incidence of burning mouth syndrome. Mayo Clin Proc 89:1545–1552CrossRefPubMedPubMedCentral Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MD (2014) A population-based study of the incidence of burning mouth syndrome. Mayo Clin Proc 89:1545–1552CrossRefPubMedPubMedCentral
3.
go back to reference Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MD (2014) The prevalence of burning mouth syndrome: a population-based study. Br J Dermatol 89:1545–52 Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MD (2014) The prevalence of burning mouth syndrome: a population-based study. Br J Dermatol 89:1545–52
4.
go back to reference Ducasse D, Courtet P, Olie E (2013) Burning mouth syndrome: current clinical, physiopathologic, and therapeutic data. Reg Anesth Pain Med 38:380–390CrossRefPubMed Ducasse D, Courtet P, Olie E (2013) Burning mouth syndrome: current clinical, physiopathologic, and therapeutic data. Reg Anesth Pain Med 38:380–390CrossRefPubMed
5.
go back to reference Mendak-Ziółko M, Konopka T, Bogucki ZA (2012) Evaluation of select neurophysiological, clinical and psychological tests for burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol 114:325–332CrossRefPubMed Mendak-Ziółko M, Konopka T, Bogucki ZA (2012) Evaluation of select neurophysiological, clinical and psychological tests for burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol 114:325–332CrossRefPubMed
6.
go back to reference Forssell H, Jääskeläinen S, Tenovuo O, Hinkka S (2002) Sensory dysfunction in burning mouth syndrome. Pain 99:41–47CrossRefPubMed Forssell H, Jääskeläinen S, Tenovuo O, Hinkka S (2002) Sensory dysfunction in burning mouth syndrome. Pain 99:41–47CrossRefPubMed
7.
go back to reference Hagelberg N, Forssell H, Rinne JO, Scheinin H, Taiminen T, Aalto S, Luutonen S, Någren K, Jääskeläinen S (2003) Striatal dopamine D1 and D2 receptors in burning mouth syndrome. Pain 101:149–154CrossRefPubMed Hagelberg N, Forssell H, Rinne JO, Scheinin H, Taiminen T, Aalto S, Luutonen S, Någren K, Jääskeläinen S (2003) Striatal dopamine D1 and D2 receptors in burning mouth syndrome. Pain 101:149–154CrossRefPubMed
8.
go back to reference Koike K, Shinozaki T, Hara K, Noma N, Okada-Ogawa A, Asano M, Shinoda M, Eliav E, Gracely RH, Iwata K, Imamura Y (2014) Immune and endocrine function in patients with burning mouth syndrome. Clin J Pain 30:168–173PubMed Koike K, Shinozaki T, Hara K, Noma N, Okada-Ogawa A, Asano M, Shinoda M, Eliav E, Gracely RH, Iwata K, Imamura Y (2014) Immune and endocrine function in patients with burning mouth syndrome. Clin J Pain 30:168–173PubMed
9.
go back to reference Kontoangelos K, Koukia E, Papanikolaou V, Chrysovergis A, Maillis A, Papadimitriou GN (2014) Suicidal behavior in a patient with burning mouth syndrome. Case Rep Psychiatry 2014:405106PubMedPubMedCentral Kontoangelos K, Koukia E, Papanikolaou V, Chrysovergis A, Maillis A, Papadimitriou GN (2014) Suicidal behavior in a patient with burning mouth syndrome. Case Rep Psychiatry 2014:405106PubMedPubMedCentral
10.
go back to reference McGirr A, Davis L, Vila-Rodriguez F (2014) Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT. Psychiatry Res 216:158–159CrossRefPubMed McGirr A, Davis L, Vila-Rodriguez F (2014) Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT. Psychiatry Res 216:158–159CrossRefPubMed
11.
go back to reference Khan SA, Keaser ML, Meiller TF, Seminowicz DA (2014) Altered structure and function in the hippocampus and medial prefrontal cortex in patients with burning mouth syndrome. Pain 155:1472–1480CrossRefPubMed Khan SA, Keaser ML, Meiller TF, Seminowicz DA (2014) Altered structure and function in the hippocampus and medial prefrontal cortex in patients with burning mouth syndrome. Pain 155:1472–1480CrossRefPubMed
12.
go back to reference Spanemberg JC, Rodríguez de Rivera Campillo E, Salas EJ, López López J (2014) Burning Mouth Syndrome: update. Oral Health Dent Manag 13:418–424PubMed Spanemberg JC, Rodríguez de Rivera Campillo E, Salas EJ, López López J (2014) Burning Mouth Syndrome: update. Oral Health Dent Manag 13:418–424PubMed
13.
go back to reference Fleuret C, Le Toux G, Morvan J, Ferreira F, Chastaing M, Guillet G, Misery L (2014) Use of selective serotonin reuptake inhibitors in the treatment of burning mouth syndrome. Dermatology 228:172–176CrossRefPubMed Fleuret C, Le Toux G, Morvan J, Ferreira F, Chastaing M, Guillet G, Misery L (2014) Use of selective serotonin reuptake inhibitors in the treatment of burning mouth syndrome. Dermatology 228:172–176CrossRefPubMed
14.
go back to reference Borsani E, Majorana A, Cocchi MA, Conti G, Bonadeo S, Padovani A, Lauria G, Bardellini E, Rezzani R, Rodella LF (2014) Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis. Histol Histopathol 29:523–533PubMed Borsani E, Majorana A, Cocchi MA, Conti G, Bonadeo S, Padovani A, Lauria G, Bardellini E, Rezzani R, Rodella LF (2014) Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis. Histol Histopathol 29:523–533PubMed
15.
go back to reference Silvestre FJ, Silvestre-Rangil J, Tamarit-Santafé C, Bautista D (2012) Application of a capsaicin rinse in the treatment of burning mouth syndrome. Med Oral Patol Oral Cir Bucal 17:e1–4CrossRefPubMed Silvestre FJ, Silvestre-Rangil J, Tamarit-Santafé C, Bautista D (2012) Application of a capsaicin rinse in the treatment of burning mouth syndrome. Med Oral Patol Oral Cir Bucal 17:e1–4CrossRefPubMed
16.
go back to reference de Moraes M, do Amaral Bezerra BA, da Rocha Neto PC, de Oliveira Soares AC, Pinto LP, de Lisboa Lopes Costa A (2012) Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature. J Oral Pathol Med 41:281–287CrossRefPubMed de Moraes M, do Amaral Bezerra BA, da Rocha Neto PC, de Oliveira Soares AC, Pinto LP, de Lisboa Lopes Costa A (2012) Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature. J Oral Pathol Med 41:281–287CrossRefPubMed
17.
go back to reference Hens MJ, Alonso-Ferreira V, Villaverde-Hueso A, Abaitua I, Posada de la Paz M (2012) Cost-effectiveness analysis of burning mouth syndrome therapy. Community Dent Oral Epidemiol 40:185–192CrossRefPubMed Hens MJ, Alonso-Ferreira V, Villaverde-Hueso A, Abaitua I, Posada de la Paz M (2012) Cost-effectiveness analysis of burning mouth syndrome therapy. Community Dent Oral Epidemiol 40:185–192CrossRefPubMed
19.
go back to reference Clifford TJ, Warsi MJ, Burnett CA, Lamey PJ (1998) Burning mouth in Parkinson’s disease sufferers. Gerodontology 15:73–78CrossRefPubMed Clifford TJ, Warsi MJ, Burnett CA, Lamey PJ (1998) Burning mouth in Parkinson’s disease sufferers. Gerodontology 15:73–78CrossRefPubMed
20.
go back to reference Prakash S, Ahuja S, Rathod C (2012) Dopa responsive burning mouth syndrome: restless mouth syndrome or oral variant of restless legs syndrome?J. Neurol Sci 320:156–156CrossRef Prakash S, Ahuja S, Rathod C (2012) Dopa responsive burning mouth syndrome: restless mouth syndrome or oral variant of restless legs syndrome?J. Neurol Sci 320:156–156CrossRef
22.
go back to reference Dieb W, Ouachikh O, Durif F, Hafidi A (2014) Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia. Brain Behav 4:368–380CrossRefPubMedPubMedCentral Dieb W, Ouachikh O, Durif F, Hafidi A (2014) Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia. Brain Behav 4:368–380CrossRefPubMedPubMedCentral
23.
go back to reference Komiyama O, Nishimura H, Makiyama Y, Iida T, Obara R, Shinoda M, Kobayashi M, Noma N, Abe O, De Laat A, Kawara M (2013) Group cognitive-behavioral intervention for patients with burning mouth syndrome. J Oral Sci 55:17–22CrossRefPubMed Komiyama O, Nishimura H, Makiyama Y, Iida T, Obara R, Shinoda M, Kobayashi M, Noma N, Abe O, De Laat A, Kawara M (2013) Group cognitive-behavioral intervention for patients with burning mouth syndrome. J Oral Sci 55:17–22CrossRefPubMed
24.
go back to reference Rodríguez-de Rivera-Campillo E, López-López J (2013) Evaluation of the response to treatment and clinical evolution in patients with burning mouth syndrome. Med Oral Patol Oral Cir Bucal 18:e403–410CrossRefPubMed Rodríguez-de Rivera-Campillo E, López-López J (2013) Evaluation of the response to treatment and clinical evolution in patients with burning mouth syndrome. Med Oral Patol Oral Cir Bucal 18:e403–410CrossRefPubMed
25.
go back to reference McMillan R, Forssell H, Buchanan JA, Glenny AM, Weldon JC, Zakrzewska JM (2016) Interventions for treating burning mouth syndrome. Cochrane Database Syst Rev 11:CD002779PubMed McMillan R, Forssell H, Buchanan JA, Glenny AM, Weldon JC, Zakrzewska JM (2016) Interventions for treating burning mouth syndrome. Cochrane Database Syst Rev 11:CD002779PubMed
26.
go back to reference Amos K, Yeoh SC, Farah CS (2011) Combined topical and systemic clonazepam therapy for the management of burning mouth syndrome: a retrospective pilot study. J Orofac Pain 25:125–30PubMed Amos K, Yeoh SC, Farah CS (2011) Combined topical and systemic clonazepam therapy for the management of burning mouth syndrome: a retrospective pilot study. J Orofac Pain 25:125–30PubMed
27.
go back to reference de Castro LA, Ribeiro-Rotta RF (2014) The effect of clonazepam mouthwash on the symptomatology of burning mouth syndrome: an open pilot study. Pain Med 15:2164–5CrossRefPubMed de Castro LA, Ribeiro-Rotta RF (2014) The effect of clonazepam mouthwash on the symptomatology of burning mouth syndrome: an open pilot study. Pain Med 15:2164–5CrossRefPubMed
28.
go back to reference Tan SN, Song E, Dong XD, Somvanshi RK, Cairns BE (2014) Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity. Arch Oral Biol 59:251–7CrossRefPubMed Tan SN, Song E, Dong XD, Somvanshi RK, Cairns BE (2014) Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity. Arch Oral Biol 59:251–7CrossRefPubMed
29.
go back to reference Besson M, Matthey A, Daali Y, Poncet A, Vuilleumier P, Curatolo M, Zeilhofer HU, Desmeules J (2015) GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers. Pain 156:397–404CrossRefPubMed Besson M, Matthey A, Daali Y, Poncet A, Vuilleumier P, Curatolo M, Zeilhofer HU, Desmeules J (2015) GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers. Pain 156:397–404CrossRefPubMed
30.
go back to reference Kacirova I, Grundmann M, Silhan P, Brozmanova H (2016) A case report of clonazepam dependence: utilization of therapeutic drug monitoring during withdrawal period. Medicine (Baltimore) 95(9):e2881CrossRef Kacirova I, Grundmann M, Silhan P, Brozmanova H (2016) A case report of clonazepam dependence: utilization of therapeutic drug monitoring during withdrawal period. Medicine (Baltimore) 95(9):e2881CrossRef
31.
go back to reference Hooten WM (2016) Chronic pain and mental health disorders: shared neural mechanisms, epidemiology, and treatment. Mayo Clin Proc 91:955–70CrossRefPubMed Hooten WM (2016) Chronic pain and mental health disorders: shared neural mechanisms, epidemiology, and treatment. Mayo Clin Proc 91:955–70CrossRefPubMed
32.
go back to reference Aiyer R, Barkin RL, Bhatia A. Treatment of Neuropathic Pain with Venlafaxine: A Systematic Review. Pain Med. 2016. [Epub ahead of print] Aiyer R, Barkin RL, Bhatia A. Treatment of Neuropathic Pain with Venlafaxine: A Systematic Review. Pain Med. 2016. [Epub ahead of print]
33.
go back to reference Richards JS, Bombardier CH, Wilson CS, Chiodo AE, Brooks L, Tate DG, Temkin NR, Barber JK, Heinemann AW, McCullumsmith C, Fann JR (2015) Efficacy of venlafaxine XR for the treatment of pain in patients with spinal cord injury and major depression: a randomized, controlled trial. Arch Phys Med Rehabil 96:680–9CrossRefPubMed Richards JS, Bombardier CH, Wilson CS, Chiodo AE, Brooks L, Tate DG, Temkin NR, Barber JK, Heinemann AW, McCullumsmith C, Fann JR (2015) Efficacy of venlafaxine XR for the treatment of pain in patients with spinal cord injury and major depression: a randomized, controlled trial. Arch Phys Med Rehabil 96:680–9CrossRefPubMed
34.
go back to reference Massaly N, Morón JA, Al-Hasani R (2016) A trigger for opioid misuse: chronic pain and stress dysregulate the mesolimbic pathway and kappa opioid system. Front Neurosci 10:480CrossRefPubMedPubMedCentral Massaly N, Morón JA, Al-Hasani R (2016) A trigger for opioid misuse: chronic pain and stress dysregulate the mesolimbic pathway and kappa opioid system. Front Neurosci 10:480CrossRefPubMedPubMedCentral
35.
go back to reference Mitsi V, Zachariou V (2016) Modulation of pain, nociception, and analgesia by the brain reward center. Neuroscience 338:81–92CrossRefPubMed Mitsi V, Zachariou V (2016) Modulation of pain, nociception, and analgesia by the brain reward center. Neuroscience 338:81–92CrossRefPubMed
36.
go back to reference Mignogna MD, Pollio A, Fortuna G, Leuci S, Ruoppo E, Adamo D, Zarrelli C (2011) Unexplained somatic comorbidities in patients with burning mouth syndrome: a controlled clinical study. J Orofac Pain 25:131–40PubMed Mignogna MD, Pollio A, Fortuna G, Leuci S, Ruoppo E, Adamo D, Zarrelli C (2011) Unexplained somatic comorbidities in patients with burning mouth syndrome: a controlled clinical study. J Orofac Pain 25:131–40PubMed
37.
go back to reference Kuten-Shorrer M, Kelley JM, Sonis ST, Treister NS (2014) Placebo effect in burning mouth syndrome: a systematic review. Oral Dis 20:e1–6CrossRefPubMed Kuten-Shorrer M, Kelley JM, Sonis ST, Treister NS (2014) Placebo effect in burning mouth syndrome: a systematic review. Oral Dis 20:e1–6CrossRefPubMed
38.
go back to reference Mo X, Zhang J, Fan Y, Svensson P, Wang K (2015) Thermal and mechanical quantitative sensory testing in Chinese patients with burning mouth syndrome--a probable neuropathic pain condition? J Headache Pain 16:84CrossRefPubMedPubMedCentral Mo X, Zhang J, Fan Y, Svensson P, Wang K (2015) Thermal and mechanical quantitative sensory testing in Chinese patients with burning mouth syndrome--a probable neuropathic pain condition? J Headache Pain 16:84CrossRefPubMedPubMedCentral
Metadata
Title
Refractory burning mouth syndrome: clinical and paraclinical evaluation, comorbidities, treatment and outcome
Authors
Dimos D. Mitsikostas
Srdjan Ljubisavljevic
Christina I. Deligianni
Publication date
01-12-2017
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2017
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-017-0745-y

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