Background & Aims

Chronic pain is a major global health problem with a global prevalence of 20% of the adult population and an annual incidence of 10% of the global adult population(1, 2). Despite its prevalence and global burden of disease of chronic pain, no objective biomarkers for pain exist which hinders “deep phenotyping” of patients and its subsequent potential (3). Therefore, we investigated structural changes and alterations of brain metabolism in a homogeneous group of individuals suffering from chronic pain. Specifically, we performed magnetic resonance imaging (MRI) and [18F]-FDG positron emission tomography computed tomography (PET-CT) of the brain of individuals suffering from persistent spinal pain syndrome type II (PSPS-II).

Methods

In this study, 26 individuals with PSPS-II (mean age 56.1 ± 8.2 years; 15 females) underwent MRI (n=16) or [18F]-FDG PET-CT (n=10). Controls included 16 for MRI- and 20 for PET imaging (mean age 58.2 ± 9.7 years; 18 females). Patients underwent a mini-mental state examination before PET-CT to exclude neurodegenerative conditions (4). MRI data were analyzed using the T1-w/T2-w technique to assess myelin content (5). Diffusion-weighted imaging analysis investigated the integrity of fifteen brain structures. [18F]-FDG PET data explored metabolic changes. SPM 12 conducted whole brain mapping analyses, with comparisons between patients and controls using unpaired T-tests.

Results

The mean ADC value of the spinothalamic tract was found to be significantly higher in PSPS-II patients compared to controls (p = 0.013). Other anatomical regions did not show statistically different ADC values between the two groups. Whole brain mapping of T1-w/T2-w data showed no significant differences in myelin content between the brain of patients and controls. However, a significantly increased volume of total white matter in patients suffering from PSPS-II patients was observed (p = 0.007). [18F]-FDG PET-CT imaging revealed significant bilateral hypermetabolism in the prefrontal cortex, supramarginal gyrus, temporal pole and inferior temporal gyrus (all p < 0.001). Additionally, the caudate nucleus showed a bilateral hypermetabolism (p < 0.001). Hypometabolism was observed in the bilateral associative visual cortex and bilateral visuo-motor cortex (all p < 0.001).

Conclusions

Current findings suggest that (micro)structural changes occur in the spinothalamic tracts of patients suffering from PSPS-II. Although we found no myelination deficits, the volume of all white matter was found to be increased in PSPS-II patients. This could be indicative of neuroplastic changes that occur in response to chronic pain, although the exact pathophysiological mechanism remains elusive. We hypothesize that the observed structural changes are the result of the widespread metabolic changes which were observed on [18F]-FDG PET data in both cortical and subcortical grey matter structures. Our metabolic findings corroborate the results of a 3-year follow-up study in which it was emphasized that the frontostriatal networks play an important role in the chronification of low back pain (6). However, no significant changes in glucose metabolism were observed in the thalamus, cingulate cortex, anterior insular cortex, or other regions that are part of the “pain neuromatrix” (7).

References

1.IASP. Unrelieved pain is a majorglobal healthcare problem: International Association for the Study of Pain; https://www.iasp-pain.org/index.aspx [
2.Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011;11:770.
3.Tracey I. Neuroimaging enters the pain biomarker arena. Sci Transl Med. 2021;13(619):eabj7358.
4.Brown RK, Bohnen NI, Wong KK, Minoshima S, Frey KA. Brain PET in suspected dementia: patterns of altered FDG metabolism. Radiographics. 2014;34(3):684-701.
5.Glasser MF, Van Essen DC. Mapping human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI. J Neurosci. 2011;31(32):11597-616.
6.Vachon-Presseau E, Tétreault P, Petre B, Huang L, Berger SE, Torbey S, et al. Corticolimbic anatomical characteristics predetermine risk for chronic pain. Brain. 2016;139(Pt 7):1958-70.
7.Brooks J, Tracey I. From nociception to pain perception: imaging the spinal and supraspinal pathways. J Anat. 2005;207(1):19-33.

Presenting Author

Dylan Henssen

Poster Authors

Dylan Henssen

MD

Radboud University Medical Center

Lead Author

E-mail

Max van Grinsven

Department of Medical Imaging, Radboud University Medical Center

Lead Author

E-mail

Lara Burmeister

BSc

Radboudumc

Lead Author

E-mail

Richard Witkam

MD

Radboudumc

Lead Author

E-mail

Kris Vissers

MD

Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center

Lead Author

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Topics

  • Novel Experimental/Analytic Approaches/Tools

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