Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain

Abstract

<jats:title>Abstract</jats:title> <jats:sec id="j_sjpain-2017-0159_s_999"> <jats:title id="d747282e717">Background and aims</jats:title> <jats:p>Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain.</jats:p></jats:sec> <jats:sec id="j_sjpain-2017-0159_s_998"> <jats:title id="d747282e725">Methods</jats:title> <jats:p>Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel <jats:sup>1</jats:sup>H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramér–Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated.</jats:p></jats:sec> <jats:sec id="j_sjpain-2017-0159_s_997"> <jats:title id="d747282e736">Results</jats:title> <jats:p>The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (<jats:italic>p</jats:italic>=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (r<jats:sub>s</jats:sub>=−0.42, <jats:italic>n</jats:italic>=28, <jats:italic>p=</jats:italic>0.031 and r<jats:sub>s</jats:sub>=−0.48, <jats:italic>n</jats:italic>=28, <jats:italic>p</jats:italic>=0.034, respectively) as well as pressure-pain threshold on the hand (r<jats:sub>s</jats:sub>=−0.41, <jats:italic>n</jats:italic>=28, <jats:italic>p</jats:italic>=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (r<jats:sub>s</jats:sub>=0.42, <jats:italic>n</jats:italic>=26, <jats:italic>p</jats:italic>=0.034).</jats:p></jats:sec> <jats:sec id="j_sjpain-2017-0159_s_996"> <jats:title id="d747282e785">Conclusions</jats:title> <jats:p>The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations.</jats:p></jats:sec> <jats:sec id="j_sjpain-2017-0159_s_995"> <jats:title id="d747282e794">Implications</jats:title> <jats:p>The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.</jats:p></jats:sec>

A comprehensive review on biomarkers associated with painful temporomandibular disorders

“…Several studies have indicated that TMD pain conditions are associated with changes in brain Metabolism. 101 In these studies, MRS imaging was used to assess neurochemical metabolites. It includes are N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr) as well as other metabolites such as glutamate (Glu), glutamine (Gln), and myo-insitol.…”

“…It includes are N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr) as well as other metabolites such as glutamate (Glu), glutamine (Gln), and myo-insitol. 101 According to the previous literature NAA is a biomarker of neuronal health and axonal numbers, while Cho is associated with in-creased cell numbers, membrane synthesis, or membrane breakdown. tCr is considered an important marker of cell energy and cell metabolism.…”

“… Zhang et al 91 , Wilcox et al 87 , He et al 98 , Moayedi et al 88 , Gustin et al 89 , Weissman-Fogel et al 94 , Ichesco et al 92 , Younger et al 90 , Buckner et al 93 Functional MRI Alterations in FC, GMV CBF, MD was observed in different regions of high order cognition, emotion-related regions such as ACC, PCC, MCCC, mPFC, DLPFC, Amygdala, and PAG-raphe system. Functional and Structural MRI In motor system: structural and functional alterations, as well as changes in cortical processing such as increased cortical thickness or elevated activity, was observed in M1 and SMA areas MRS Neurochemical changes: alterations in NAA, Cho, and tCr levels were observed in patients with TMD pain Harfeldt et al 101 , Feraco et al 105 , Fayed et al 104 , Harris et al 102 , 103 QST Sensory functioning QST studies observed abnormalities in somatosensory profile as well as enhanced pain sensitivity in patients with TMJ arthralgia and myofascial pain Wang et al 116 , Zhou et al 108 , Yang et al 110 , 112 , Kothari et al 111 Pain genetics SNPs in COMT gene Glucocorticoid receptor gene-HPA axis, serotonin receptor gene-nociceptive afferent pathways, alpha subunit of the voltage-gated sodium channel Nav1.1-action potential in sensory nerves, prostaglandin-endoperoxide synthase 1 gene-nociceptive and inflammatory response, amyloid beta (A4) precursor protein- synapse formation and neuronal plasticity, PDZ domain protein gene-affects G protein-coupled receptors involved in nociception and analgesia. Serotonin receptor HTR2A, ERA as well as genetic and epigenetic factors such as SLC64A4, TRPV2, MYT1L, and NRXN3 along with environmental factors play a vital role in the development of chronic TMD pain.…”

Can you be too old for oral implants? An update on ageing and plasticity in the oro‐facial sensorimotor system

“…Likewise in relation to oro‐‐facial sensorimotor functions, the failure of patients to adapt to changes in the oral cavity, or the development of a chronic sensorimotor condition, may reflect oro‐facial malplasticity. For instance, brain‐imaging studies in humans have shown that temporomandibular disorders (TMD) or bruxism may be associated with structural and functional changes that occur in several brain regions involved in oro‐facial sensorimotor functions and that have been considered to reflect malplasticity; the CNS regions affected include the oro‐facial sensorimotor area and the supplementary motor area.…”

Biomarkers in temporomandibular disorder and trigeminal neuralgia: A conceptual framework for understanding chronic pain

“…104 A more recent MRS study found increased total creatine in the posterior insula of patients with TMD and, furthermore, that increased choline and glutamate concentrations in the posterior insular cortex were correlated with clinical characteristics of TMD pain, including generalized pain. 105 Because MRI is a standard diagnostic tool in TN and is critical to evaluation for surgical treatments of TN, almost all patients with TN undergo neuroimaging. However, research MRIs often use specialized protocols and postprocessing techniques not typically used in clinical practice.…”