Investigation of 1H MRS changes in the brain of osteoarthritis patients in relation to perceived pain
Franklyn Arron Howe1, Olakunbi Harrison2, Thomas Richard Barrick1, and Nidhi Sofat2

1Neuroscience Research Centre, St George's, University of London, London, United Kingdom, 2Institute for Infection and Immunity, St George's, University of London, London, United Kingdom

Synopsis

Chronic pain from osteoarthritis (OA) may be aggravated by “central sensitisation”, whereby pain-processing pathways become sensitised by inflammatory and degenerative disease processes. 1H MRS was used to investigate biochemical changes in pain processing brain areas of hand OA patients (n=32) compared to controls (n=14). There were no differences between controls and patients in the anterior cingulate gyrus, nor age related changes. In the insula cortex mI/Glx correlated with the pain score (R2 = 0.52, p = 0.018) after co-varying for age. High mI/Glx in the insula cortex was associated with high pain and may reflect inflammatory effects or neurological changes.

Purpose

Chronic pain due to osteoarthritis (OA) may be aggravated by “central sensitisation”, whereby pain-processing pathways become sensitised by inflammatory and degenerative disease processes1. We used 1H Magnetic Resonance Spectroscopy (MRS) to investigate whether there were biochemical changes in pain processing regions of the brain2 that could be related to perceived pain in patients with hand OA.

Methods

MR acquisition: Data were acquired at 3T using PRESS single voxel localisation with TE 32ms TR 2000ms and 96 averages. Voxels were planned on 3D T1w images and placed in the anterior cingulate gyrus (voxel size 25 x 20 x 10 mm3) and insula cortex (voxel size 25 x 10 x 15 mm3). Metabolite levels were determined using LCModel™ as ratios to total creatine (tCr) to avoid the confound of CSF partial volumes. Data were only included for SNR > 8 and CRLB < 12% for the major metabolites of NAA, tCr, tCho, mI and Glx (Glu plus Gln).

Patients: Data were acquired on 32 hand OA patients (ages 49 to 76 yr) and 14 controls with no history of OA or chronic pain (ages 43 to 71 yr). Clinical scores were available for 22 patients as measured by visual analogue scale (VAS) for self-reported pain, painDETECT, the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) and the Hospital Anxiety and Depression Scale (HADS).

Analysis: Statistical analyses were made with SPSS for linear correlations between MRS measures and clinical scores, Principal Component Analysis (PCA) with Varimax rotation, and a t-test for group comparisons.

Results

An initial group comparison of was made with age-matched OA patients (63 ± 5 yr), for which there was a significant difference in VAS pain scores (n= 5 per group, VAS 5.2 ± 4 and VAS 8 ± 0.7 with p = 0.0079). There was no significant difference in NAA/tCr or tCho/tCr between these groups. However Glx/tCr was reduced, mI/tCr was increased and mI/Glx was significantly increased in patients (0.34 ± 0.03 v. 0.45 ± 0.08, p = 0.017) suggesting mI/Glx may be a useful biomarker relating to pain.

Over the full age range, there were no metabolite differences found between controls and OA participants in the anterior cingulate gyrus or insula cortex. Also, there were no age related changes of metabolite ratios in either region in the controls or in the anterior cingulate gyrus of OA patients. However, in the insula cortex of OA patients the mI/Glx ratio was positively correlated with age (R2 = 0.29, p = 0.0018, see Figure 1) and with VAS pain score after co-varying for age (R2 = 0.52, p = 0.018).

Since clinical scores of pain and related symptoms such as depression and anxiety are related, we performed Principal Component Analysis (PCA) across all clinical scores as a data reduction method to find which scores are related to MRS in the OA patient subgroup. Three PCs described 71% of the variance: PC1 was strongly weighted by AUSCAN pain and anxiety scores; PC2 by HADS anxiety and depression scores; PC3 by AUSCAN stiffness, painDETECT and VAS pain score. Using a ranked PC and mI/Glx correlation to minimise the effect of outliers, we found PC3 was correlated to mI/Glx (R2 = 0.188, p = 0.049, see Figure 2), with a stronger correlation after co-varying for age (R2 = 0.46, p = 0.041).

Discussion

The correlation of insular cortex mI/Glx to PC3 of the clinical scores supports our initial hypothesis of this metabolite ratio being a biomarker relevant to perceived pain. However, how this metabolite ratio changes in relation to OA pain may not be straightforward, since in those age < 65 yr, mI/Glx is lower in OA patients than controls, and for patients aged > 65 yr there is elevated mI/Glx compared to controls (see Fig 1). Increased myo-Inositol has been observed in neuro-inflammation3 and an increase in glutamate has been associated with acute pain stimulation4. Hence there could be disease related changes in mI and Glx that are dependent on patient age and/or disease duration.

Acknowledgements

This work was supported by the Rosetrees Trust and St George’s Hospital Charity.

References

1. Scholz C & Woolf CJ. Nature Neuroscience 2002; 5:1062-1067

2. Sofat N et al. Journal of Biomedical Graphics and Computing 2013; 3(4). doi: 10.5430/jbgc.v3n4p20

3. Chang L et al J. Neuroimmune Pharmacol 2013; 8:576–593

4. Gussew A et al. NeuroImage 2010; 49:1895–1902

Figures

Figure 1 Linear regression indicates a correlation of mI/Glx ratio in the insula cortex of hand OA patients with R2 = 0.29 and p = 0.0018, but no age related changes in controls.

Figure 2 Correlation of PC3 from PCA of the clinical scores to mI/Glx of the insula cortex in OA patients (R2 = 0.188, P = 0.049). PC3 was strongly weighted by AUSCAN stiffness, painDETECT and VAS pain scores.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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