title: Diminished supraspinal pain modulation in patients with mild traumatic brain injury.
abstract: Chronic pain conditions are highly prevalent in patients with mild traumatic brain injury. Supraspinal diffuse axonal injury is known to dissociate brain functional connectivity in these patients. The effect of this dissociated state on supraspinal pain network is largely unknown. A functional magnetic resonance imaging study was conducted to compare the supraspinal pain network in patients with mild traumatic brain injury to the gender and age-matched healthy controls with the hypothesis that the functional connectivities of the medial prefrontal cortices, a supraspinal pain modulatory region to other pain-related sensory discriminatory and affective regions in the mild traumatic brain injury subjects are significantly reduced in comparison to healthy controls.
  
  
  
  The mild traumatic brain injury group (N = 15) demonstrated significantly (P < 0.01, cluster threshold > 150 voxels) less activities in the thalamus, pons, anterior cingulate cortex, insula, dorsolateral prefrontal cortex, and medial prefrontal cortices than the healthy control group (N = 15). Granger Causality Analyses (GCA) indicated while the left medial prefrontal cortices of the healthy control group cast a noticeable degree of outward (to affect) causality inference to multiple pain processing related regions, this outward inference pattern was not observed in the mild traumatic brain injury group. On the other hand, only patients' bilateral anterior cingulate cortex received multiple inward (to be affected) causality inferences from regions including the primary and secondary somatosensory cortices and the inferior parietal lobe. Resting state functional connectivity analyses indicated that the medial prefrontal cortices of the mild traumatic brain injury group demonstrated a significantly (P < 0.01, F = 3.6, cluster size > 150 voxels) higher degree of functional connectivity to the inferior parietal lobe, premotor and secondary somatosensory cortex than the controls. Conversely, the anterior cingulate cortex of the healthy group demonstrated significantly (P < 0.01, F = 3.84, cluster size > 150 voxels) less degree of functional connectivities to the inferior parietal lobe and secondary somatosensory cortex than their mild traumatic brain injury counterparts.
  
  
  
  In short, the current study demonstrates that patients with mild traumatic brain injury and headaches appear to have an altered state of supraspinal modulatory and affective functions related to pain perception.
authors.affiliation: Department of Anesthesiology, The University of California, San Diego, CA, USA Veteran Administration San Diego Healthcare System, San Diego, CA, USA ayleung@ucsd.edu.
authors.forename: Albert
authors.initials: A
authors.lastname: Leung
authors.affiliation: Department of Anesthesiology, The University of California, San Diego, CA, USA Veteran Administration San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Shivshil
authors.initials: S
authors.lastname: Shukla
authors.affiliation: The University of California, San Diego, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Yang
authors.affiliation: The University of California, San Diego, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Canlas
authors.affiliation: The University of California, San Diego, USA.
authors.forename: Mawj
authors.initials: M
authors.lastname: Kadokana
authors.affiliation: Drexel University, College of Medicine, Philadelphia, PA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Heald
authors.affiliation: St. Louis School of Medicine, St. Louis, MO, USA.
authors.forename: Ariea
authors.initials: A
authors.lastname: Davani
authors.affiliation: Veteran Administration San Diego Healthcare System, San Diego, CA, USA Department of Neuroscience, The University of California, San Diego, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Song
authors.affiliation: Veteran Administration San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, The University of California, San Diego, CA, USA Veteran Administration San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Polston
authors.affiliation: Veteran Administration San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Tsai
authors.affiliation: Veteran Administration San Diego Healthcare System, San Diego, CA, USA Department of Radiology, The University of California, San Diego, CA, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Lee
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D058748:Pain Perception / Q000502:physiology*
keywords: Traumatic brain injury; chronic posttraumatic headaches; functional magnetic resonance imaging; mild traumatic brain injury; pain; resting state functional connectivity; supraspinal pain processing