Metabolite concentrations in the anterior cingulate cortex predict high neuropathic pain impact after spinal cord injury

Abstract

Persistent pain is a common reason for reduced quality of life after a spinal cord injury (SCI). Biomarkers of neuropathic pain may facilitate translational research and the understanding of underlying mechanisms. Research suggests that pain and affective distress are anatomically and functionally integrated in the anterior cingulate cortex and can modulate sensory and affective aspects of pain. We hypothesized that severe neuropathic pain with a significant psychosocial impact would be associated with metabolite concentrations (obtained by magnetic resonance spectroscopy) in the anterior cingulate cortex, indicating neuronal and/or glial dysfunction. Participants with SCI and severe, high-impact neuropathic pain (SCI-HPI; n=16), SCI and moderate, low-impact neuropathic pain (SCI-LPI; n=24), SCI without neuropathic pain (SCI-noNP; n=14), and able-bodied, pain-free control subjects (A-B; n=22) underwent a 3-T magnetic resonance imaging brain scan. Analyses revealed that the SCI-HPI group had significantly higher levels of myoinositol (Ins) (P<.000), creatine (P=.007), and choline (P=.014), and significantly lower levels of N-acetyl aspartate/Ins (P=.024) and glutamate-glutamine (Glx)/Ins (P=.003) ratios than the SCI-LPI group. The lower Glx/Ins ratio significantly discriminated between SCI-HPI and the A-B (P=.006) and SCI-noNP (P=.026) groups, displayed excellent test-retest reliability, and was significantly related to greater pain severity, interference, and affective distress. This suggests that the combination of lower glutamatergic metabolism and proliferation of glia and glial activation are underlying mechanisms contributing to the maintenance of severe neuropathic pain with significant psychosocial impact in chronic SCI. These findings indicate that the Glx/Ins ratio may be a useful biomarker for severe SCI-related neuropathic pain with significant psychosocial impact.

Conflict of interest statement

None of the authors have a conflict of interest with the present work.

Published by Elsevier B.V.

Figures

Fig. 1

Voxel placement over the anterior cingulate cortex.

Fig. 2

Comparisons between the A-B, SCI-noNP, SCI-LPI, and SCI-HPI groups with regard to psychosocial factors: BDI, STAI, and SWLS. Analysis of variance with post hoc Dunnett adjustment comparing the SCI-HPI with the A-B, SCI-noNP, and SCI-LPI showed that the SCI-HPI group had significantly higher BDI and STAI scores than the A-B (P < .000), SCI-noNP (P < .000), and SCI-LPI (P < .000); and that the SCI-HPI group had significantly lower SWLS scores than the A-B (P = .001), SCI-noNP (P = .001), and SCI-LPI (P = .044). A-B = able-bodied control subject; BDI = Beck Depression Inventory; SCI-HPI = spinal cord injury with high pain impact; SCI-LPI = spinal cord injury with low pain impact; SCI-noNP = spinal cord injury without neuropathic pain; STAI = Spielberger Trait Anxiety Inventory; SWLS = Satisfaction with Life Scale.

Fig. 3

Three scatter plot diagrams that illustrate the relationship between the Multidimensional Pain Inventory–Spinal Cord Injury subscales Pain Severity, Life Interference, and Affective Distress, and the Glx/Ins ratio. Glx/Ins = glutamate-glutamine/myoinositol.