Subacute Pain after Traumatic Brain Injury Is Associated with Lower Insular N-Acetylaspartate Concentrations.
Persistent pain is experienced by more than 50% of persons who sustain a traumatic brain injury (TBI), and more than 30% experience significant pain as early as 6 weeks after injury. Although neuropathic pain is a common consequence after CNS injuries, little attention has been given to neuropathic pain symptoms after TBI. Magnetic resonance spectroscopy (MRS) studies in subjects with TBI show decreased brain concentrations of N-acetylaspartate (NAA), a marker of neuronal density and viability. Although decreased brain NAA has been associated with neuropathic pain associated with spinal cord injury (SCI) and diabetes, this relationship has not been examined after TBI. The primary purpose of this study was to test the hypothesis that lower NAA concentrations in brain areas involved in pain perception and modulation would be associated with greater severity of neuropathic pain symptoms. Participants with TBI underwent volumetric MRS, pain and psychosocial interviews. Cluster analysis of the Neuropathic Pain Symptom Inventory subscores resulted in two TBI subgroups: The Moderate Neuropathic Pain (n = 17; 37.8%), with significantly (p = 0.038) lower insular NAA than the Low or no Neuropathic Pain group (n = 28; 62.2%), or age- and sex-matched controls (n = 45; p < 0.001). A hierarchical linear regression analysis controlling for age, sex, and time post-TBI showed that pain severity was significantly (F = 11.0; p < 0.001) predicted by a combination of lower insular NAA/Creatine (p < 0.001), lower right insular gray matter fractional volume (p < 0.001), female sex (p = 0.005), and older age (p = 0.039). These findings suggest that neuronal dysfunction in brain areas involved in pain processing is associated with pain after TBI.
1 The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, University of Miami Miller School of Medicine , Miami, Florida.|3 Department of Physical Medicine and Rehabilitation, University of Miami Miller School of Medicine , Miami, Florida.
Eva
E
Widerström-Noga
4 Department of Radiology, University of Miami Miller School of Medicine , Miami, Florida.
Varan
V
Govind
1 The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine , Miami, Florida.
James P
JP
Adcock
5 Department of Neurology, University of Miami Miller School of Medicine , Miami, Florida.
Bonnie E
BE
Levin
4 Department of Radiology, University of Miami Miller School of Medicine , Miami, Florida.
Andrew A
AA
Maudsley
D000328:Adult; D000367:Age Factors; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000150:complications*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009437:Neuralgia / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine
MRI spectroscopy; N-acetylaspartate; biomarkers; central pain; traumatic brain injury