Is Burning Mouth Syndrome a Neuropathic Pain Disorder? A Systematic Review

Aims: To conduct a systematic review compiling an update on the pathophysiology of burning mouth syndrome (BMS) by reviewing the theories and studies published in the last 5 years that consider BMS a neuropathic disease. Methods: A literature review was carried out in April 2020 on the PubMed database by using the following MeSH terms: “(burning mouth OR burning mouth syndrome OR burning mouth pain OR sore mouth OR burning tongue OR oral neuropathic pain OR glossodynia OR stomatopyrosis) AND (etiopathogenesis OR etiopathological factors OR etiology).” Results: The research carried out according to the methodology found 19 case-control studies (1 of which was in vivo) and 1 RCT. Of the 19 included studies, 8 showed an evidence score of 2–; 8 showed 2+; another 2 showed 2++; and 1 showed 1+. Quality studies on this topic are insufficient and heterogenous. Conclusion: In the pathogenesis of BMS, both peripheral and central neuropathies appear to play a pivotal role. Nevertheless, the balance between them varies from case to case and tends to overlap. BMS does not seem to be a result of direct damage to the somatosensory nervous system, but a dysfunction in it and in the brain network.

burning mouth syndrome; etiology; neuropathy; pain disorder

1. Imamura Y, Shinozaki T, Okada-Ogawa A, et al. An updated review on pathophysiology and management of burning mouth syndrome with endocrinological, psychological and neuropathic perspec-tives. J Oral Rehabil 2019;46:574–587.

2. Silvestre FJ, Silvestre-Rangil J, López-Jornet P. Burning mouth syndrome: A review and update. Rev Neurol 2015;60:457–463.

3. Treldal C, Jacobsen CB, Mogensen S, et al. Effect of a local anesthetic lozenge in relief of symptoms in burning mouth syndrome. Oral Dis 2016;22:123–131.

4. Spanemberg JC, Rodríguez de Rivera Campillo E, Salas EJ, López López J. Burning mouth syndrome: Update. Oral Health Dent Manag 2014;13:418–424.

5. Kim MJ, Kho HS. Understanding of burning mouth syndrome based on psychological aspects. Chin J Dent Res 2018;21:9–19.

6. Liu YF, Kim Y, Yoo T, Han P, Inman JC. Burning mouth syndrome: A systematic review of treatments. Oral Dis 2018;24:325–334.

7. Feller L, Fourie J, Bouckaert M, Khammissa RAG, Ballyram R, Lemmer J. Burning mouth syndrome: Aetiopathogenesis and prin-ciples of management. Pain Res Manag 2017;2017:1926269.

8. Beneng K, Renton T. Pain part 8: Burning mouth syndrome. Dent Update 2016;43:254–266.

9. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211.

10. Araz C, Askin S, Yilmaz C. Herpes zoster brachial plexopathy: Direct steroid injection. Turk Neurosurg 2017;7:662–664.

11. Baird AG, Lawrence J. Guidelines: Is bigger better? A review of SIGN guidelines. BMJ Open 2014;4:1–5.

12. Liu BL, Yao H, Zheng XJ, et al. Low regional cerebral blood flow in burning mouth syndrome patients with depression. Oral Dis 2015;21:602–607.

13. Jääskeläinen SK. Is burning mouth syndrome a neuropathic pain condition? Pain 2018;159:610–613.

14. Shinoda M, Noma N. Pathophysiology and treatment of orofacial pain. Clin Calcium 2017;27:1375–1382.

15. Barry A, O’Halloran KD, McKenna JP, McCreary C, Downer EJ. Plasma IL-8 signature correlates with pain and depressive symptomatology in patients with burning mouth syndrome: Results from a pilot study. J Oral Pathol Med 2018;47:158–165.

16. Mo X, Zhang J, Fan Y, Svensson P, Wang K. Thermal and mechanical quantitative sensory testing in Chinese patients with burn-ing mouth syndrome—A probable neuropathic pain condition? J Headache Pain 2015;16:84.

17. López-Jornet P, Molino-Pagan D, Parra-Pérez P, Valenzuela S. Neuropathic pain in patients with burning mouth syndrome evaluated using painDETECT. Pain Med 2017;18:1528–1533.

18. Heo JY, Ok SM, Ahn YW, Ko MY, Jeong SH. The application of neuropathic pain questionnaires in burning mouth syndrome patients. J Oral Facial Pain Headache 2015;29:177–182.

19. Zavoreo I, Vucˇic`evic` V, Boras, et al. The significance of brain transcranial sonography in burning mouth syndrome: A pilot study. Acta Stomatol Croat 2017;51:48–59.

20. Adamo D, Sardella A, Varoni E, et al. The association between burning mouth syndrome and sleep disturbance: A case-control multicentre study. Oral Dis 2018;24:638–649.

21. Sikora M, Verzak Ž, Matijevic` M, et al. Anxiety and depression scores in patients with burning mouth syndrome. Psychiatr Danub 2018;30:466–470.

22. Kolkka M, Forssell H, Virtanen A, Puhakka A, Pesonen U, Jääskeläinen SK. Neurophysiology and genetics of burning mouth syndrome. Eur J Pain 2019;23:1153–1161.

23. López-Jornet P, Lucero-Berdugo M, Castillo-Felipe C, Zamora Lavella C, Ferrandez-Pujante A, Pons-Fuster A. Assessment of self-reported sleep disturbance and psychological status in patients with burning mouth syndrome. J Eur Acad Dermatol Venereol 2015;29:1285–1290.

24. Watanabe K, Noma N, Sekine N, et al. Association of somatosensory dysfunction with symptom duration in burning mouth syn-drome. Clin Oral Investig 2019;23:3471–3477.

25. Nasri-Heir C, Shigdar D, Alnaas D, Korczeniewska OA, Eliav R, Heir GM. Primary burning mouth syndrome: Literature review and preliminary findings suggesting possible association with pain modulation. Quintessence Int 2017;49:49–60.

26. Sinding C, Gransjøen AM, Schlumberger G, Grushka M, Frasnelli J, Singh PB. Grey matter changes of the pain matrix in patients with burning mouth syndrome. Eur J Neurosci 2016;43:997–1005.

27. Wada A, Shizukuishi T, Kikuta J, et al. Altered structural connec-tivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography. Neuroradiology 2017;59:525–532.

28. Shinozaki T, Imamura Y, Kohashi R, et al. Spatial and temporal brain responses to noxious heat thermal stimuli in burning mouth syndrome. J Dent Res 2016;95:1138–1146.

29. Yoshino A, Okamoto Y, Doi M, et al. Functional alterations of postcentral gyrus modulated by angry facial expressions during intraoral tactile stimuli in patients with burning mouth syndrome: A functional magnetic resonance imaging study. Front Psychiatry 2017;8:224.

30. Khursheed F, Ioffe J, Gould HJ 3rd. A plea for rational mitigation of poor outcomes in the ‘off-label use’ of medications for the management of pain. J Neurol Sci 2015;349:72–76.

31. Freynhagen R, Serpell M, Emir B, et al. A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain. Pain Pract 2015;15:47–57.

32. Ito M, Tokura T, Yoshida K, et al. Five patients with burning mouth syndrome in whom an antidepressant (serotonin-noradrenaline reuptake inhibitor) was not effective, but pregabalin markedly relieved pain. Clin Neuropharmacol 2015;38:158–161.

33. Madariaga VI, Tanaka H, Ernberg M. Psychophysical characterisation of burning mouth syndrome—A systematic review and me-ta-analysis. J Oral Rehabil 2020;47:1590–1605.

34. Yilmaz Z, Renton T, Yiangou Y, et al. Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score. J Clin Neurosci 2007;14:864–871.

35. Shinoda M, Takeda M, Honda K, et al. Involvement of peripheral artemin signaling in tongue pain: Possible mechanism in burning mouth syndrome. Pain 2015;156:2528–2537.

36. Imura H, Shimada M, Yamazaki Y, Sugimoto K. Characteristic changes of saliva and taste in burning mouth syndrome patients. J Oral Pathol Med 2016;45:231–236.

37. Acharya S, Carlén A, Wenneberg B, Jontell M, Hägglin C. Clinical characterization of women with burning mouth syndrome in a case-control study. Acta Odontol Scand 2018;76:279–286.

38. Kolkka-Palomaa M, Jääskeläinen SK, Laine MA, Teerijoki-Oksa T, Sandell M, Forssel H. Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: A review. Oral Dis 2015;21:937–948.

39. Kohashi R, Shinozaki T, Sekine N, et al. Time-dependent responses in brain activity to ongoing hot stimulation in burning mouth syn-drome. J Oral Sci 2020;62:170–174.

40. Hartmann A, Seeberger R, Bittner M, Rolke R, Welte-Jzyk C, Daubländer M. Profiling intraoral neuropathic disturbances following lingual nerve injury and in burning mouth syndrome. BMC Oral Health 2017;17:68.

41. Puhakka A, Forssell H, Soinila S, et al. Peripheral nervous system involvement in primary burning mouth syndrome—Results of a pilot study. Oral Dis 2016;22:338–344.

42. Lee YC, Hong IK, Na SY, et al. Evaluation of salivary function in patients with burning mouth syndrome. Oral Dis 2015;21:308–313.

43. Braud A, Descroix V, Ungeheuer MN, Rougeot C, Boucher Y. Taste function assessed by electrogustometry in burning mouth syndrome: A case-control study. Oral Dis 2017;23:395–402.

44. O’Neill F. Corneal confocal microscopy detects small-fiber neu-ropathy in burning mouth syndrome: A crosssectional study. J Oral Facial Pain Headache 2019;33:337–341.