MRI-Based Neuroimaging of Chronic Orofacial Pain in Temporomandibular Joint Dysfunction Comorbid with Anxiety and Depression
https://doi.org/10.52667/2712-9179-2025-5-3-3-12
Abstract
A study of the brain using magnetic resonance morphometry and diffusion tensor imaging in patients with chronic orofacial pain syndrome associated with temporomandibular joint pain dysfunction syndrome revealed changes in regional gray matter volume, namely a decrease in the volume of the primary somatosensory cortex, an increase in gray matter volume in the thalamus, and an increase in both volume and microstructural alterations in the brainstem (in the dorsal horn of the midbrain) accompanied by changes in diffusion properties, specifically an increase in mean diffusivity; in the projection of structures of the descending pain modulation system, including the periaqueductal gray matter of the midbrain and the nucleus raphe magnus, as well as in the integrity of ascending pain pathways (a reduction of fractional anisotropy in the trigeminal root entry zone, the spinal trigeminal tract, and the ventral trigemino-thalamic tract); as well as bilateral increases in the gray matter volume of the pons corresponding to the principal sensory nucleus of the trigeminal nerve.
The aim of this study is to analyze current data concerning MRI neuroimaging methods of the central nervous system in patients with chronic orofacial pain syndrome in temporomandibular joint pain dysfunction syndrome comorbid with anxiety and depression. We analyzed more than 60 articles in English devoted to neuroimaging studies using voxel-based morphometry of the central nervous system in patients with chronic orofacial pain syndrome in temporomandibular joint pain dysfunction syndrome comorbid with anxiety and depression. The rapid development of imaging in recent decades has led to an increase in the number of identified causes of dysfunction in the trigeminal nerve system, which are amenable to specific treatment and functional recovery. A clinically oriented segmental approach to trigeminal nerve pathology is important for conducting specialized high-resolution imaging studies, which are a powerful tool in the examination of patients with trigeminal nerve dysfunction.
About the Authors
Yulia V. KotsiubinskayaRussian Federation
St. Petersburg, 192019
Evgeniy V. Efimov
Russian Federation
St. Petersburg, 192019
Ruslana V. Grebenshchikova
Russian Federation
St. Petersburg, 192019
Ilia K. Stulov
Russian Federation
St. Petersburg, 192019
References
1. Valesan; L.F.; Da-Cas; C.D.; Réus; J.C.; Denardin; A.C.S.; Garanhani; R.R.; Bonotto; D.; Januzzi; E.; de Souza; B.D.M. Prevalence of temporomandibular joint disorders: a systematic review and meta-analysis. Clin Oral Investig. 2021; 25(2); 441-453. doi:10.1007/s00784-020-03710-w
2. Gauer; R.L.; Semidey; M.J. Diagnosis and treatment of temporomandibular disorders. Am Fam Physician .2015; 91(6):378-86
3. List; T.; Jensen; R.H. Temporomandibular disorders: Old ideas and new concepts. Cephalalgia. 2017; 37(7):692-704. doi: 10.1177/0333102416686302
4. Thumati; P. The influence of immediate complete anterior guidance development technique on subjective symptoms in Myofascial pain patients: Verified using digital analysis of occlusion (Tek-scan) for analysing occlusion: A 3 years clinical observation. J Indian Prosthodont Soc. 2015; 15(3):218. doi: 10.4103/0972-4052.158079
5. Thumati; P.; Poovani; S.; Ayinala; M. A retrospective five-year survey on the treatment outcome of Disclusion Time Reduction (DTR) therapy in treating temporomandibular dysfunction patients. Cranio. 2021; 41(6):494-500. doi: 10.1080/08869634.2021.1887609
6. Manfredini; D.; Guarda-Nardini; L.; Winocur; E.; Piccotti; F.; Ahlberg; J.; Lobbezoo; F. Research diagnostic criteria for temporo- mandibular disorders: a systematic review of axis I epidemio- logic findings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 112:453–462. doi.: 10.1016/j.tripleo.2011.04.021
7. Moayedi; M.; Weissman-Fogel; I.; Crawley; A.P.; Crawley; A.P.; Goldberg; M.B.; Freeman; B.V.; Tenenbaum; H.C.; Davis; K.D. Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder. Neuroimage. 2011; 55(1):277-86. doi: 10.1016/j.neuroimage.2010.12.013
8. Gerstner; G.; Ichesco; E.; Quintero; A.; Schmidt-Wilcke; T. Changes in regional gray and white matter volume in patients with myofascial-type temporomandibular disorders: a voxel-based morphometry study. J Orofac Pain. 2011; 25(2):99-106
9. Yin; Y.; He; S.; He; N.; Zhang; W.; Luo; L.; Chen; L.; Liu; T.; Tian; M.; Xu; J.; Chen; S.; Li; F. Brain alterations in sensorimotor and emotional regions associated with temporomandibular disorders. Oral Dis. 2024; 30(3):1367-1378. doi: 10.1111/odi.14466
10. Moulton; E.A.; Pendse; G.; Morris; S.; Strassman; A.; Aiello-Lammens; M.; Becerra; L.; Borsook; D. Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: an fMRI study. Neuroimage. 2007; 35: 1586–600. doi: 10.1016/j.neuroimage.2007.02.001
11. Younger; J.W.; Shen; Y.F.; Goddard; G.; Mackey; S.C. Chronic myofascial temporo-mandibular pain is associated with neural abnormalities in the trigeminal and limbic systems. Pain. 2010; 149: 222-228. doi: 10.1016/j.pain.2010.01.006
12. Wilcox; S.L.; Gustin; S.M.; Macey; P.M.; Peck; C.C.; Murray; G.M.; Henderson; L. A. Anatomical changes within the medullary dorsal horn in chronic temporomandibular disorder pain. Neuroimage. 2015; 117:258-66. doi: 10.1016/j.neuroimage.2015.05.014
13. Brooks; J.C.W.; Nurmikko; T.J.; Bimson; W.E.; Singh; K.D.; Roberts; N. FMRI of thermal pain: effects of stimulus laterality and attention. Neuroimage. 2002; 15: 293–301. doi: 10.1006/nimg.2001.0974
14. Symonds; L.L.; Gordon; N.S.; Bixby; J.C.; Mande; M.M. Right-lateralized pain processing in the human cortex: an FMRI study. J Neurophysiol. 2006; 95: 3823–30. doi: 10.1152/jn.01162.2005
15. May; A. Chronic pain may change the structure of the brain. Pain. 2008; 137: 7-15. doi: 10.1016/j.pain.2008.02.034
16. Flor; H. Cortical reorganisation and chronic pain: implications for rehabilitation. J Rehabil Med. 2003; 66–72. doi: 10.1080/16501960310010179
17. Teutsch; S.; Herken; W.; Bingel; U.; Schoell; E.; May; A. Changes in brain gray matter due to repetitive painful stimulation. Neuroimage. 2008; 42:845–9. doi: 10.1016/j.neuroimage.2008.05.044
18. Woolf; C.J.; Salter; M.W. Neuronal plasticity: increasing the gain in pain. Science. 2000; 288:1765–9. doi: 10.1126/science.288.5472.1765
19. Apkarian; A.V.; Baliki; M.N.; Geha; P.Y. Towards a theory of chronic pain. Prog Neurobiol. 2009; 87:81–97. doi: 10.1016/j.pneurobio.2008.09.018
20. Purves; D.; Augustine; G.; Fitzpatrick; D.; Katz; L.; LaMantia; A.; McNamara; J.; Williams; M. Thalamocortical Interactions. Neuroscience. Sinauer. 2001; Available from: https://www.ncbi.nlm.nih.gov/books/NBK11000/
21. Valfrè; W.; Rainero; I.; Bergui; M.; Pinessi; L. Voxel-based morphometry reveals gray matter abnormalities in migraine. Headache. 2008; 48:109–17. doi: 10.1111/j.1526-4610.2007.00723
22. Schmidt-Wilcke; T.; Leinisch; E.; Straube; A.; Kämpfe; N.; Draganski; B.; Diener; H.C.; Bogdahn; U.; May; A. Gray matter decrease in patients with chronic tension type headache. Neurology. 2005; 65:1483–6. doi: 10.1212/01.wnl.0000183067.94400.80
23. Schmidt-Wilcke; T.; Luerding; R.; Weigand; T.; Jürgens; T.; Schuierer; G.; Leinisch; E.; Bogdahn; U. Striatal grey matter increase in patients suffering from fibromyalgia – a voxel-based morphometry study. Pain. 2007; 1:S109-S116. doi:10.1016/j.pain.2007.05.010
24. Schmidt-Wilcke; T.; Gänssbauer; S.; Neuner; T.; Bogdahn; U.; May; A. Subtle grey matter changes between migraine patients and healthy controls. Cephalalgia. 2008; 28:1–4. doi:10.1111/j.1468-2982.2007.01428.x
25. Teutsch; S.; Herken; W.; Bingel; U.; Schoell; E.; May; A. Changes in brain gray matter due to repetitive painful stimulation. Neuroimage. 2008; 42:845–9. doi:10.1016/j.neuroimage.2008.05.044
26. Gerstner; G.; Ichesco; E.; Quintero; A.; Schmidt-Wilcke T. Changes in regional gray and white matter volume in patients with myofascial-type temporomandibular disorders: a voxel-based morphometry study. J Orofac Pain. 2011; 25:99-106.
27. Rodriguez-Raecke; R.; Niemeier; A.; Ihle; K.; Ruether; W.; May; A. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. Neurosci. 2009; 29(44):13746-50. doi:10.1523/JNEUROSCI.3687-09.2009
28. Festa; F.; Rotelli; C.; Scarano; A.; Navarra; R.; Caulo; M.; Macrì; M. Functional magnetic resonance connectivity in patients with temporomadibular joint disorders. Frontiers in Neurology. 2021; 12: 629211. doi:10.3389/fneur.2021.629211
29. Jääskeläinen; S.K.; Rinne; J.O.; Forssell; H.; Tenovuo; O.; Kaasinen; V.; Sonninen; P.; Bergman; J. Role of the dopaminergic system in chronic pain – a fluorodopa- PET study. Pain. 2001; 90:257–60. doi:10.1016/S0304-3959(00)00409-7
30. Chen; T.C.; Lin; C.S. Neuroimaging meta-analysis of brain mechanisms of the association between orofacial pain and mastication. J Oral Rehabil. 2023; 50(10):1070-1081. doi:10.1111/joor.13526
31. Mechelli; A.; Friston; K.J.; Frackowiak; R.S.; Price; C.J. Structural covariance in the human cortex. J Neurosci. 2005; 25:8303–10. doi:10.1523/JNEUROSCI.0357-05.2005
32. Eriksson; S.H.; Free; S.L.; Thom; M.; Symms; M.R.; Martinian; L.; Duncan; J.S.; Sisodiya; S.M. Quantitative grey matter histological measures do not correlate with grey matter probability values from in vivo MRI in the temporal lobe. J Neurosci Methods. 2009; 181:111–8. doi:10.1016/j.jneumeth.2009.05.001
33. Fernandez-de-las-Penas; C.; Svensson; P. Myofascial Temporomandibular Disorder. Current Rheumatology Reviews. 2016; 12(1):40-54. doi:10.2174/1573397112666151231110947
34. Leblebici; B.; Pektas; Z.O.; Ortancil; O.; Hürcan; E.C.; Bagis; S.; Akman; M.N. Coexistence of fibromyalgia; temporomandibular disorder; and masticatory myofascial pain syndromes. Rheumatol Int. 2007; 27:541–4. doi:10.1007/s00296-006-0251-z
35. Phillips; M.L.; Young; A.W.; Senior; C.; Brammer; M.; Andrew; C.; Calder; A.J.; Bullmore; E.T.; Perrett; D.I.; Rowland; D.; Williams; S.C.; Gray; J.A.; David; A.S. A specific neural substrate for perceiving facial expressions of disgust. Nature. 1997; 389:495–8. doi:10.1038/39051
36. Craig; A.D. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol. 2003; 13:500–5. doi:10.1016/s0959-4388(03)00090-4
37. Craig; A.D. How do you feel – now? The anterior insula and human awareness. Nat Rev Neurosci. 2009; 10:59–70. doi:10.1038/nrn2555
38. Singer; T.; Seymour; B.; O’Doherty; J.; Kaube; H.; Dolan; R.J.; Frith; C.D. Empathy for pain involves the affective but not sensory components of pain. Science. 2004; 303: 1157–62. doi:10.1126/science.1093535
39. Lovero; K.L.; Simmons; A.N.; Aron; J.L.; Paulus; M.P. Anterior insular cortex anticipates impending stimulus significance. Neuroimage. 2009; 45:976–83. doi:10.1016/j.neuroimage.2008.12.070
40. Borsook; D.; Upadhyay; J.; Chudler; E.H.; Becerra; L. A key role of the basal ganglia in pain and analgesia--insights gained through human functional imaging. Mol Pain. 2010; 13:6:27. doi:10.1186/1744-8069-6-27
41. Bingel; U.; Gläscher; J.; Weiller; C.; Büchel; C. Somatotopic representation of nociceptive information in the putamen: an event-related fMRI study. Cereb Cortex. 2004; 14:1340–5. doi:10.1093/cercor/bhh094
42. Bingel; U.; Schoell; E.; Herken; W.; Büchel; C.; May; A. Habituation to painful stimulation involves the antinociceptive system. Pain. 2007; 131:21–30. doi:10.1016/j.pain.2006.12.005
43. Iadarola; M.J.; Berman; K.F.; Zeffiro; T.A.; Byas-Smith; M.G.; Gracely; R.H.; Max; M.B.; Bennett; G.J. Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. Brain. 1998; 121:931–47. doi:10.1093/brain/121.5.931
44. Kuchinad; A.; Schweinhardt; P.; Seminowicz; D.A.; Wood; P.B.; Chizh; B.A.; Bushnell; M.C. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci. 2007; 27:4004–7. doi:10.1523/JNEUROSCI.0098-07.2007
45. Davis; K.D.; Pope; G.; Chen; J.; Kwan; C.L.; Crawley; A.P.; Diamant; N.E. Cortical thinning in IBS: implications for homeostatic; attention; and pain processing. Neurology. 2008; 70:153–4. doi:10.1212/01.wnl.0000295509.30630.10
46. Critchley; H.D.; Wiens; S.; Rotshtein; P.; Ohman; A.; Dolan; R.J. Neural systems supporting interoceptive awareness. Nat Neurosci. 2004; 7:189–95. doi:10.1038/nn1176
47. Rossetti; M.G.; Delvecchio; G.; Calati; R.; Perlini; C.; Bellani; M.; Brambilla; P. Structural neuroimaging of somatoform disorders: A systematic review. Neuroscience & Biobehavioral Reviews. 2020; 122:66-78. doi:10.1016/j.neubiorev.2020.12.017
48. Périard; I. A.; Dierolf; A.M.; Lutz; A.; Vögele; C.; Voderholzer; U.; Koch; S.; Bach; M.; Asenstorfer; C.; Michaux; G.; Mertens; V.C.; Schulz; A. Frontal alpha asymmetry is associated with chronic stress and depression; but not with somatoform disorders. Int J Psychophysiol. 2024; 200:112342. doi:10.1016/j.ijpsycho.2024.112342
49. Delvecchio; G.; Rossetti; M.G;; Caletti; E.; Arighi; A.; Galimberti; D.; Basilico; P.; Mercurio; M.; Paoli; R.; Cinnante; C.; Triulzi; F.; Altamura; A.C.; Scarpini; E.; Brambilla; P. The Neuroanatomy of Somatoform Disorders: A Magnetic Resonance Imaging Study. Psychosomatics. 2019; 60(3): 278-288. doi:10.1016/j.psym.2018.07.005
50. Lin; J.; Cao; D.Y. Associations Between Temporomandibular Disorders and Brain Imaging-Derived Phenotypes. International dental journal. 2024; 74(4): 784-793. doi: 10.1016/j.identj.2024.01.008
Review
For citations:
Kotsiubinskaya Yu.V., Efimov E.V., Grebenshchikova R.V., Stulov I.K. MRI-Based Neuroimaging of Chronic Orofacial Pain in Temporomandibular Joint Dysfunction Comorbid with Anxiety and Depression. Personalized Psychiatry and Neurology. 2025;5(3):3-12. https://doi.org/10.52667/2712-9179-2025-5-3-3-12