TY - JOUR
T1 - Metabolite concentrations in the anterior cingulate cortex predict high neuropathic pain impact after spinal cord injury
AU - Widerström-Noga, Eva
AU - Pattany, Pradip M.
AU - Cruz-Almeida, Yenisel
AU - Felix, Elizabeth R.
AU - Perez, Salome
AU - Cardenas, Diana D.
AU - Martinez-Arizala, Alberto
N1 - Funding Information:
The authors gratefully acknowledge excellent technical assistance by Mr. James Adcock, Ms. Letitia Fisher, and Mr. Qing He. This work was supported by the Department of Veterans Affairs Office of Rehabilitation Research and Development Service (Merit Review grant B5023R), and The Miami Project. None of the authors have a conflict of interest with the present work.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Cingulate cortex
KW - Magnetic resonance spectroscopy
KW - Neuropathic pain
KW - Psychosocial impact
KW - Spinal cord injury
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U2 - 10.1016/j.pain.2012.07.022
DO - 10.1016/j.pain.2012.07.022
M3 - Article
C2 - 23141478
AN - SCOPUS:84872675173
VL - 154
SP - 204
EP - 212
JO - Pain
JF - Pain
SN - 0304-3959
IS - 2
ER -