TABLE 3.

Evaluation of cortical alterations in CBP patients using the MRS technique.

Author, year	Methods	Patients	Controls	Main findings (patients compared with controls)
Grachev et al., 2000	1H-MRS	Nine CLBP	11 Healthy controls	•Alterations in the human brain chemistry in patients •Decreased NAA and Glu in the dlPFC •No chemical concentration differences in brain regions, such as the cingulate, sensorimotor, etc. •Abnormal interrelationship between chemicals within and across brain regions •A specific correlation between regional chemical concentration and perceptual scores of anxiety and pain
Grachev et al., 2001	1H-MRS	Nine CBP	16 Healthy controls	•Alterations in NAA levels of the dlPFC and OFC •Correlations between the levels of brain regional NAA (the OFC and dlPFC) and perceptual measures of pain in CBP patients •Correlation between the NAA changes of the OFC and measures of anxiety in CBP patients
Grachev et al., 2002	1H-MRS	12 CLBP with symptoms of anxiety	16 Healthy controls	•An exact correlation between perception and brain chemical contents •The dlPFC and OFC were considered as the best related chemical-perceptual network to pain •The relationship between chemical-anxiety networks was best related to the OFC chemistry in controls and to the dlPFC, OFC, cingulate, and thalamus in CLBP patients •The region best related to the affective component of pain was the cingulate cortex
Grachev et al., 2003	1H-MRS	10 CBP with depression	10 Healthy controls	•Decreased NAA levels in the right dlPFC •Strong correlation between depression levels of CBP patients and the levels of NAA levels in the right dlPFC •Weak correlation between the levels of pain levels and levels of NAA in the right dlPFC of CBP patients (compared to depression-NAA correlations)
Gussew et al., 2011	1H-MRS	10 CLBP	10 Healthy controls	•Decreased levels of Glu in the ACC •Decreased levels of Gln in the anterior INS, ACC, and thalamus •Decreased levels of NAA in the anterior INS and ACC •Decreased levels of mI was reduced in the ACC and thalamus •No significant changes for Cr
Sharma et al., 2011	1H-MRS	11 CLBP	11 Healthy controls	•Correlations between metabolite concentrations and pain characteristics •Decreased NAA and Cho in the left S1 •Lower correlations between all metabolites (NAA, Cho, mI, Glu, and Gln) in the right S1 •Higher and significant correlations between left and right mI levels and between left mI and right Cho •Negative correlation between left and right NAA levels and pain duration •Positive correlation between right Glu/Gln concentrations and pain severity •Significant changes in the neuronal–glial interactions in S1
Sharma et al., 2012	1H-MRS	19 CLBP	14 Healthy controls	•Lower right M1 NAA •No significant differences in the Left M1 NAA and mI •No significant correlations between pain characteristics and M1 neurochemical contents
Siddall et al., 2006	1H-MRS	32 CLBP	33 Healthy controls	•Significant differences in the chemical levels of ACC, thalamus, and PFC of patients compared with the ones of healthy subjects with accuracies of 100%, 99%, and 97%, respectively

¹H-MRS, single-voxel proton magnetic resonance spectroscopy; CBP, chronic back pain; CLBP, chronic low back pain; NAA, N-acetyl aspartate; Glu, glutamate; Gln, glutamine; Cr, creatine; mI, myo-inositol; Cho, choline; PFC, prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; OFC, orbital frontal cortex; INS, insula; S1, primary somatosensory cortex; M1, primary motor cortex.