Thalamic Neurometabolite Alterations in Chronic Low Back Pain: A Common Phenomenon across Musculoskeletal Pain Conditions?

Abstract

A previous study by our group showed that knee osteoarthritis (KOA) patients demonstrate alterations in the thalamic levels of several metabolites, as measured by 1H-magnetic resonance spectroscopy: i.e., higher myo-inositol (mIns), lower N-acetylaspartate (NAA) and lower Choline (Cho), when compared to healthy controls. We sought to replicate these results in a different musculoskeletal pain condition, chronic low back pain (cLBP), and explore whether these metabolites would resolve clinical subtypes of cLBP. Twenty-nine cLBP patients (twenty-two with axial low back pain, cLBPAX, and seven with radicular low back pain, cLBPRAD), and twenty healthy controls were scanned using a conventional PRESS sequence (TE=30ms; TR=1.7s; voxel size=15 × 15 × 15mm) with voxel placement in the left thalamus. Using water-normalized levels, cLBP patients demonstrated higher mIns (p<0.01), lower NAA (p<0.001) and lower Cho (p<0.05) than healthy controls, replicating our prior KOA results in this cLBP cohort. Additionally, NAA was reduced in cLBPAX when compared to cLBPRAD (p<0.05), whereas differences found in Cho and mIns were not statistically significant (p<0.20 and p<0.15, respectively). While pain severity scores were not correlated with metabolite levels, the degree of nociplastic pain, as measured by score on the American College of Rheumatology Fibromyalgia Survey, negatively correlated with NAA. These results suggest that thalamic metabolite changes may be common across spatially different musculoskeletal chronic pain conditions for mIns, a marker of glial dysfunction, NAA, a marker of neuronal integrity, and Cho, a membrane turnover marker. Additionally, the differences between cLBP subtypes suggest that neuronal integrity may have a role to play in the pathophysiology of nociplastic pain. Grant support from 1-R01-NS094306-01A1 (MLL); 1-R01-NS09593701A1 (MLL).