title: 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.
authors.affiliation: Research Service, Department of Veterans Affairs Medical Center, Miami, FL, USA The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL, USA Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA Department of Rehabilitation Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA Neuroscience Graduate Program, Miller School of Medicine, University of Miami, Miami, FL, USA Department of Radiology, Miller School of Medicine, University of Miami, Miami, FL, USA Spinal Cord Injury Service, Department of Veterans Affairs Medical Center, Miami, FL, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Widerström-Noga
authors.forename: Pradip M
authors.initials: PM
authors.lastname: Pattany
authors.forename: Yenisel
authors.initials: Y
authors.lastname: Cruz-Almeida
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Felix
authors.forename: Salome
authors.initials: S
authors.lastname: Perez
authors.forename: Diana D
authors.initials: DD
authors.lastname: Cardenas
authors.forename: Alberto
authors.initials: A
authors.lastname: Martinez-Arizala
mesh_terms: D000328:Adult; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D059408:Pain Management; D010147:Pain Measurement; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism*
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D007294:Inositol; D003401:Creatine; D002794:Choline