Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain.
BACKGROUND
Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up.


METHODS
Seventy-seven mTBI patients initially underwent neuropsychological measurements, 9-plex panel of serum cytokines and MRI scans within 7 days post-injury (T-1) and 54 (70.1%) of patients completed the same protocol at a 3-month follow-up (T-2). Forty-two matched healthy controls completed the same protocol at T-1 once.


RESULTS
At baseline, mTBI patients with APTH presented significantly increased GM volume mainly in the right dorsal anterior cingulate cortex (dACC) and dorsal posterior cingulate cortex (dPCC), of which the dPCC volume can predict much worse impact of headache on patients' lives by HIT-6 (β = 0.389, P = 0.007) in acute stage. Serum levels of C-C motif chemokine ligand 2 (CCL2) were also elevated in these patients, and its effect on the impact of headache on quality of life was partially mediated by the dPCC volume (mean [SE] indirect effect, 0.088 [0.0462], 95% CI, 0.01-0.164). Longitudinal analysis showed that the dACC and dPCC volumes as well as CCL2 levels had persistently increased in patients developing CPTH 3 months postinjury.


CONCLUSION
The findings suggested that structural remodelling of DMN brain regions were involved in the progression from acute to chronic PTH following mTBI, which also mediated the effect of inflammation processes on pain modulation.


TRIAL REGISTRATION
ClinicalTrial.gov ID: NCT02868684 ; registered 16 August 2016.
['Niu|Xuan|X|', 'Bai|Lijun|L|', 'Sun|Yingxiang|Y|', 'Wang|Yuan|Y|', 'Bai|Guanghui|G|', 'Yin|Bo|B|', 'Wang|Shan|S|', 'Gan|Shuoqiu|S|', 'Jia|Xiaoyan|X|', 'Liu|Hongjuan|H|']
D001924:Brain Concussion D059350:Chronic Pain D000082702:Default Mode Network D006801:Humans D007249:Inflammation D008279:Magnetic Resonance Imaging D011788:Quality of Life
Mild traumatic brain injury Posttraumatic headache Inflammation effect Voxel-based morphometry