Accessible Unlicensed Requires Authentication Published by De Gruyter April 13, 2018

Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain

Kristin Harfeldt, Louise Alexander, Julia Lam, Sven Månsson, Hans Westergren, Peter Svensson, Pia C. Sundgren and Per Alstergren


Background and aims

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.


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 1H-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.


The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs=−0.42, n=28, p=0.031 and rs=−0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=−0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034).


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.


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.


The authors would like to thank the coordinating MR nurse Anetta Bolejko and the MR staff at Skånes University Hospital, Malmö, Sweden as well as all the participating patients.

  1. Authors’ statements

  2. Research funding: This study is partly supported by a grant from Region Skåne, Sweden (OFRS).

  3. Conflict of interest: The authors of this work have no conflicts of interest to report.

  4. Informed consent: Written informed consent was obtained from all participants.

  5. Ethical approval: The study was approved by the Regional Ethics Review Board in Lund, Sweden (2016/006) and conducted according to the provisions of the Helsinki Declaration.


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Received: 2017-11-06
Revised: 2018-02-26
Accepted: 2018-03-06
Published Online: 2018-04-13
Published in Print: 2018-07-26

©2018 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved