Background & Aims
Chronic pain remains a leading cause of disability given its high global prevalence [1-3], which aetiology remains largely elusive. Neuroimaging biomarkers could potentially offer objective phenotypical measures of the central processing of the pain experience. The ratio of the magnetic resonance imaging (MRI) based T1-weighted (T1w) and T2-weighted (T2w) image intensity (rT1/T2) has been proposed as a non-invasive biomarker for cortical myelin, neurite density, tissue integrity[4] and neuroinflammation[5]. However, this method has not been utilized in the context of chronic pain yet. Therefore, this study investigates the use of rT1/T2 maps of the brain as a novel imaging biomarker for chronic pain in post-stroke patients with central neuropathic pain (CNP) and persistent spinal pain syndrome type 2 (PSPS-II). By investigating two groups with different central causalities, we assessed whether the patterns of microstructural alterations are shared or are unique to a specific syndrome.
Methods
MRI data of patients suffering from CNP or PSPS-II were retrospectively included alongside MRI data from non-painful, healthy controls. A custom pipeline was utilized to generate the rT1/T2 images. In summary, bias correction and intensity normalization was applied to the T1-weighted and T2-weighted images, which were subsequently divided to generate the rT1/T2 maps of the brain. Furthermore, parenchymal defects present in the CNP group were manually segmented and excluded from the analysis. Voxel-wise whole brain analyses were carried out in SPM12. The normality of the data was tested by the Shapiro-Wilk normality test, for differences in age an independent T-test was used, and differences in sex distribution were assessed using a Fischer’s exact test. Significance was assumed for the descriptive statistics and whole-brain analysis if the uncorrected p-values were p<0.05 and p<0.001, respectively.
Results
In total, 15 PSPS-II patients and 11 post-stroke patients suffering from CNP were included. The control group consisted of 18 subjects. The mean age at onset in the PSPS-II and CNP group was 57.9 years (± 9.7 years) and 64.3 years (± 12.5 years), respectively. Within the control group the average age was 60.5 years (± 13.0 years). No statistically significant differences in age and sex distribution were found.
Whole brain analysis revealed four clusters of significant decreased rT1/T2 signal in the CNP group as compared to healthy controls in the dorsal and medial part of the thalamus. Additionally, the left caudate, cuneus, superior frontal gyrus and dorsal cervicomedullary junction show significant reductions in rT1/T2 signal. No significant changes were found in rT1/T2 signal intensity between PSPS-II patients and CNP patients and between PSPS-II patients and healthy controls.
Conclusions
These findings suggest that microstructural alterations occur in the thalamus, cuneus, superior frontal gyrus and dorsal cervicomedullary junction in patients with CNP. The decrease in rT1/T2 signal could be an argument against a role for a central neuro-inflammatory component. The lack of significant findings in the PSPS-II group suggests different pathophysiological mechanisms underlying both chronic pain syndromes. However, given the inherent limitations of this pilot study, further research is warranted.
References
1.Fayaz, A., et al., Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies. BMJ Open, 2016. 6(6): p. e010364.
2.Rikard, S.M., et al., Chronic Pain Among Adults – United States, 2019-2021. MMWR Morb Mortal Wkly Rep, 2023. 72(15): p. 379-385.
3.Sá, K.N., et al., Prevalence of chronic pain in developing countries: systematic review and meta-analysis. Pain Rep, 2019. 4(6): p. e779.
4.Glasser, M.F. and D.C. Van Essen, Mapping human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI. J Neurosci, 2011. 31(32): p. 11597-616.
5.Sandrone, S., et al., Mapping myelin in white matter with T1-weighted/T2-weighted maps: discrepancy with histology and other myelin MRI measures. Brain Struct Funct, 2023. 228(2): p. 525-535.
6.Dydyk, A.M. and T. Conermann, Chronic Pain, in StatPearls. 2024, StatPearls Publishing
Copyright © 2024, StatPearls Publishing LLC.: Treasure Island (FL).
7.Xia, M., J. Wang, and Y. He, BrainNet Viewer: a network visualization tool for human brain connectomics. PLoS One, 2013. 8(7): p. e68910.
Presenting Author
Maxvan Grinsven
Poster Authors
Topics
- Pain Imaging