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Gray Matter Brain Alterations in Temporomandibular Disorder Tested in a Population Cohort and Three Clinical Samples

Published:January 30, 2021DOI:https://doi.org/10.1016/j.jpain.2021.01.003

      Highlights

      • Testing the brain´s gray matter volume (GMV) in temporomandibular disorder (TMD).
      • TMD patients showed a reduction of GMV in anterior cingulate and med. frontal cortex.
      • GMV in population based participants with chronic face pain showed no reduction.

      Abstract

      Temporomandibular pain (TMD) is a frequent symptom comprising pain around the mandibular jaw with a high dependence on stressors. Chronic pain has been associated with changes of the brains gray matter volume (GMV), but previous studies on GMV alterations associated with TMD have yielded contradictory results. This might be caused by divergent samples and study methods. We here tested GMV alterations using voxel based morphometry in three clinical samples (summing up to 47 TMD patients) and a population sample with 57 participants who indicated facial pain for the last 6 months. The GMV of pain patients was compared against age-matched and gender-matched participants without chronic pain (60 for the clinical sample comparison and 381 for the cohort sample comparison) who underwent the same assessments as the patient group (MRI measurements and data evaluation using CAT12). In a region of interest analysis, only the clinical samples showed an effect of decreased GMV in the anterior medial cingulate cortex reaching into the medial prefrontal cortex, known to be especially vulnerable for chronic pain gray matter volume reduction. The analysis of the population-based sample did not reveal relevant GMV differences.
      Overall, an important question remains as to whether most inconsistent results from voxel based morphometry-studies in chronic pain are related to chance results facilitated by small sample size and selection of patient samples.

      Perspective

      Using voxel based morphometry 2 samples with chronic temperomandibular pain were compared to controls investigating the brains GMV. Only the clinical sample showed a decrease in anterior cingulate GMV. Contradicting results on GMV loss in temperomandibular pain might be based on small samples in prior studies.

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      References

        • Apkarian AV
        • Sosa Y
        • Sonty S
        • Levy RM
        • Harden RN
        • Parrish TB
        • Gitelman DR
        Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.
        J Neurosci. 2004; 24: 10410-10415https://doi.org/10.1523/JNEUROSCI.2541-04.2004
        • Ashburner J
        A fast diffeomorphic image registration algorithm.
        Neuroimage. 2007; 38: 95-113https://doi.org/10.1016/j.neuroimage.2007.07.007
        • Bonato LL
        • Quinelato V
        • De Felipe Cordeiro PC
        • De Sousa EB
        • Tesch R
        • Casado PL.
        Association between temporomandibular disorders and pain in other regions of the body.
        J Oral Rehabil. 2017; 44: 9-15https://doi.org/10.1111/joor.12457
        • Cauda F
        • Palermo S
        • Costa T
        • Torta R
        • Duca S
        • Vercelli U
        • Geminiani G
        • Torta DME
        Gray matter alterations in chronic pain: A network-oriented meta-analytic approach.
        NeuroImage Clin. 2014; 4: 676-686https://doi.org/10.1016/j.nicl.2014.04.007
        • Cohen J
        Statistical Power Analysis for the Behavioural Sciences.
        Lawrence Earlbaum Assoc, Hillside, NJ1988https://doi.org/10.1111/1467-8721.ep10768783
        • Dworkin SF
        • Sherman J
        • Mancl L
        • Ohrbach R
        • LeResche L
        • Truelove E
        Reliability, validity, and clinical utility of the research diagnostic criteria for temporomandibular disorders axis II scales: Depression, non-specific physical symptoms, and graded chronic pain.
        J Orofac Pain. 2002; 16: 207-220
        • Eickhoff SB
        • Nichols TE
        • Laird AR
        • Hoffstaedter F
        • Amunts K
        • Fox PT
        • Bzdok D
        • Eickhoff CR
        Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation.
        Neuroimage. 2016; 137: 70-85https://doi.org/10.1016/j.neuroimage.2016.04.072
        • Ernst M
        • Schenkenberger AE
        • Domin M
        • Kordass B
        • Lotze M
        Effects of centric mandibular splint therapy on orofacial pain and cerebral activation patterns.
        Clin Oral Investig. 2019; 24: 2005-2013https://doi.org/10.1007/s00784-019-03064-y
        • Fatoye F
        • Gebrye T
        • Odeyemi I
        Real-world incidence and prevalence of low back pain using routinely collected data.
        Rheumatol Int. 2019; 39: 619-626https://doi.org/10.1007/s00296-019-04273-0
        • Fearon CG
        • Serwatka WJ
        Stress: A common denominator for nonorganic TMJ pain-dysfunction.
        J Prosthet Dent. 1983; 49: 805-808https://doi.org/10.1016/0022-3913(83)90354-2
        • Friebel U
        • Eickhoff SB
        • Lotze M
        Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain.
        Neuroimage. 2011; 58: 1070-1080https://doi.org/10.1016/j.neuroimage.2011.07.022
        • Fritz HC
        • McAuley JH
        • Wittfeld K
        • Hegenscheid K
        • Schmidt CO
        • Langner S
        • Lotze M
        Chronic back pain is associated with decreased prefrontal and anterior insular gray matter: Results from a population-based cohort study.
        J Pain. 2016; 17: 111-118https://doi.org/10.1016/j.jpain.2015.10.003
        • Gesch D
        • Bernhardt O
        • Alte D
        • Schwahn C
        • Kocher T
        • John U
        • Hensel E
        Prevalence of signs and symptoms of temporomandibular disorders in an urban and rural German population: Results of a population-based Study of Health in Pomerania.
        Quintessence Int. 2004; 35: 143-150
        • Guo C
        • Shi Z
        • Revington P
        Arthrocentesis and lavage for treating temporomandibular joint disorders.
        Cochrane Database Syst Rev. 2015; https://doi.org/10.1002/14651858.CD004973.pub3
        • Gustin SM
        • Peck CC
        • Wilcox LS
        • Nash PG
        • Murray GM
        • Henderson LA
        Different pain, different brain: Thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes.
        J Neurosci. 2011; 31: 5956-5964https://doi.org/10.1523/JNEUROSCI.5980-10.2011
        • Hahm S
        • Lotze M
        • Domin M
        • Schmidt S
        The association of health-related quality of life and cerebral gray matter volume in the context of aging: A voxel-based morphometry study with a general population sample.
        Neuroimage. 2019; 191: 470-480https://doi.org/10.1016/j.neuroimage.2019.02.035
        • Helkimo M
        Studies on function and dysfunction of the masticatory system. II. Index for anamnestic and clinical dysfunction and occlusal state.
        Sven Tandlak Tidskr. 1974; 67: 101-121
        • Henderson L
        • Peck CC
        • Petersen ET
        • Rae CD
        • Youssef AM
        • Reeves JM
        • Wilcox SL
        • Akhter R
        • Murray GM
        • Gustin SM
        Chronic pain: Lost inhibition?.
        J Neurosci. 2013; 33: 7574-7582https://doi.org/10.1523/JNEUROSCI.0174-13.2013
        • Iwata K
        • Imamura Y
        • Honda K
        • Shinoda M
        Physiological mechanisms of neuropathic pain: The orofacial region.
        Int Rev Neurobiol. 2011; 97: 227-250https://doi.org/10.1016/B978-0-12-385198-7.00009-6
        • Jia Z
        • Yu S
        Grey matter alterations in migraine: A systematic review and meta-analysis.
        NeuroImage Clin. 2017; 14: 130-140https://doi.org/10.1016/j.nicl.2017.01.019
        • Kang D
        • McAuley JH
        • Kassem MS
        • Gatt JM
        • Gustin SM
        What does the grey matter decrease in the medial prefrontal cortex reflect in people with chronic pain?.
        Eur J Pain (United Kingdom). 2019; 23: 203-219https://doi.org/10.1002/ejp.1304
        • Labus JS
        • Naliboff B
        • Kilpatrick L
        • Liu C
        • Ashe-McNalley C
        • Dos Santos IR
        • Alaverdyan M
        • Woodworth D
        • Gupta A
        • Ellingson BM
        • Tillisch K
        • Mayer EA
        Pain and Interoception Imaging Network (PAIN): A multimodal, multisite, brain-imaging repository for chronic somatic and visceral pain disorders.
        Neuroimage. 2016; 124: 1232-1237https://doi.org/10.1016/j.neuroimage.2015.04.018
        • Lickteig R
        • Lotze M
        • Kordass B
        Successful therapy for temporomandibular pain alters anterior insula and cerebellar representations of occlusion.
        Cephalalgia. 2013; 33: 1248-1257https://doi.org/10.1177/0333102413491028
        • Macfarlane TV
        • Blinkhorn AS
        • Davies RM
        • Kincey J
        • Worthington HV
        Oro-facial pain in the community: Prevalence and associated impact.
        Community Dent Oral Epidemiol. 2002; 30: 52-60https://doi.org/10.1034/j.1600-0528.2002.300108.x
        • Magariños AM
        • McEwen BS
        • Flügge G
        • Fuchs E
        Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews.
        J Neurosci. 1996; 16: 3534-3540https://doi.org/10.1523/jneurosci.16-10-03534.1996
        • Martins RJ
        • Garbin CAS
        • Garcia AR
        • Garbin AJÍ
        • Miguel N
        Stress levels and quality of sleep in subjects with temporomandibular joint dysfunction.
        Rev Odonto Ciência. 2011; 48: 692-696https://doi.org/10.1590/s1980-65232010000100007
        • May A
        Chronic pain may change the structure of the brain.
        Pain. 2008; 137: 7-15https://doi.org/10.1016/j.pain.2008.02.034
        • Moayedi M
        • Weissman-Fogel I
        • Crawley AP
        • Goldberg MB
        • Freeman BV
        • Tenenbaum HC
        • Davis KD
        Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder.
        Neuroimage. 2011; 55: 277-286https://doi.org/10.1016/j.neuroimage.2010.12.013
        • Okeson JP
        • De Kanter RJAM
        Temporomandibular disorders in the medical practice.
        J Fam Pract. 1996; 43: 347-356
        • Riley JD
        • Le V
        • Der-Yeghiaian L
        • See J
        • Newton JM
        • Ward NS
        • Cramer SC
        Anatomy of stroke injury predicts gains from therapy.
        Stroke. 2011; 42: 421-426https://doi.org/10.1161/STROKEAHA.110.599340
        • Schiffman E
        • Ohrbach R
        • Truelove E
        • Look J
        • Anderson G
        • Goulet J-P
        • List T
        • Svensson P
        • Gonzalez Y
        • Lobbezoo F
        • Michelotti A
        • Brooks SL
        • Ceusters W
        • Drangsholt M
        • Ettlin D
        • Gaul C
        • Goldberg LJ
        • Haythornthwaite JA
        • Hollender L
        • Maixner W
        • van der Meulen M
        • Murray GM
        • Nixdorf DR
        • Palla S
        • Petersson A
        • Pionchon P
        • Smith B
        • Visscher CM
        • Zakrzewska J
        • Dworkin SF
        Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications: Recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†.
        J Oral Facial Pain Headache. 2014; 28: 6-27https://doi.org/10.11607/jop.1151
        • Schiffman EL
        • Ohrbach R
        • Truelove EL
        E: The Research Diagnostic Criteria for Temporomandibular Disorders. V: Methods used to establish and validate revised Axis I diagnostic algorithms.
        J Orofac Pain. 2010; 24 (Toll-like): 63-78https://doi.org/10.1002/ana.22528
        • Schmidt-Wilcke T
        • Leinisch E
        • Gänßbauer S
        • Draganski B
        • Bogdahn U
        • Altmeppen J
        • May A
        Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients.
        Pain. 2006; 125: 89-97https://doi.org/10.1016/j.pain.2006.05.004
        • Smallwood RF
        • Laird AR
        • Ramage AE
        • Parkinson AL
        • Lewis J
        • Clauw DJ
        • Williams DA
        • Schmidt-Wilcke T
        • Farrell MJ
        • Eickhoff SB
        • Robin DA
        Structural brain anomalies and chronic pain: A quantitative meta-analysis of gray matter volume.
        J Pain. 2013; 1: 663-675https://doi.org/10.1016/j.jpain.2013.03.001
        • Stein S
        • Loft G
        • Davis H
        • Hart DL
        Symptoms of TMJ dysfunction as related to stress measured by the social readjustment rating scale.
        J Prosthet Dent. 1982; 47: 545-548https://doi.org/10.1016/0022-3913(82)90307-9
        • Tohka J
        • Zijdenbos A
        • Evans A
        Fast and robust parameter estimation for statistical partial volume models in brain MRI.
        Neuroimage. 2004; 23: 84-97https://doi.org/10.1016/j.neuroimage.2004.05.007
        • Turner BO
        • Paul EJ
        • Miller MB
        • Barbey AK
        Small sample sizes reduce the replicability of task-based fMRI studies.
        Commun Biol. 2018; 1: 62https://doi.org/10.1038/s42003-018-0073-z
        • Tzourio-Mazoyer N
        • Landeau B
        • Papathanassiou D
        • Crivello F
        • Etard O
        • Delcroix N
        • Mazoyer B
        • Joliot M
        Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.
        Neuroimage. 2002; 15: 273-289https://doi.org/10.1006/nimg.2001.0978
        • Valfrè W
        • Rainero I
        • Bergui M
        • Pinessi L
        Voxel-based morphometry reveals gray matter abnormalities in migraine.
        Headache. 2008; 48: 109-117https://doi.org/10.1111/j.1526-4610.2007.00723.x
        • Vogt BA
        • Berger GR
        • Derbyshire SWG
        Structural and functional dichotomy of human midcingulate cortex.
        Eur J Neurosci. 2003; 18: 3134-3144https://doi.org/10.1111/j.1460-9568.2003.03034.x
        • Völzke H
        • Alte D
        • Schmidt CO
        • Radke D
        • Lorbeer R
        • Friedrich N
        • Aumann N
        • Lau K
        • Piontek M
        • Born G
        • Havemann C
        • Ittermann T
        • Schipf S
        • Haring R
        • Baumeister SE
        • Wallaschofski H
        • Nauck M
        • Frick S
        • Arnold A
        • Jünger M
        • Mayerle J
        • Kraft M
        • Lerch MM
        • Dürr M
        • Reffelmann T
        • Empen K
        • Felix SB
        • Obst A
        • Koch B
        • Gläser S
        • Ewert R
        • Fietze I
        • Penzel T
        • Dören M
        • Rathmann W
        • Haerting J
        • Hannemann M
        • Röpcke J
        • Schminke U
        • Jürgens C
        • Tost F
        • Rettig R
        • Kors JA
        • Ungerer S
        • Hegenscheid K
        • Kühn JP
        • Kühn J
        • Hosten N
        • Puls R
        • Henke J
        • Gloger O
        • Teumer A
        • Homuth G
        • Völker U
        • Schwahn C
        • Holtfreter B
        • Polzer I
        • Kohlmann T
        • Grabe HJ
        • Rosskopf D
        • Kroemer HK
        • Kocher T
        • Biffar R
        • John U
        • Hoffmann W
        Cohort profile: The study of health in Pomerania.
        Int J Epidemiol. 2011; 40: 294-307https://doi.org/10.1093/ije/dyp394
        • Wilcox SL
        • Gustin SM
        • Eykman EN
        • Fowler G
        • Peck CC
        • Murray GM
        • Henderson LA
        Trigeminal nerve anatomy in neuropathic and non-neuropathic orofacial pain patients.
        J Pain. 2013; 14: 865-872https://doi.org/10.1016/j.jpain.2013.02.014
        • Yeh WZ
        • Blizzard L
        • Taylor BV
        What is the actual prevalence of migraine?.
        Brain Behav. 2018; 8: e00950https://doi.org/10.1002/brb3.950
        • Younger JW
        • Shen YF
        • Goddard G
        • Mackey SC
        Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems.
        Pain. 2010; 149: 222-228https://doi.org/10.1016/j.pain.2010.01.006