Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain

Abstract

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：77 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). 42 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.

Patients with chronic mild or moderate traumatic brain injury have abnormal longitudinal brain volume enlargement more than atrophy

“…Given the a priori finding of an association, the Bonferroni adjustment may have been too conservative. 46 Overall, this finding of an association between the neuropathic headaches and abnormal enlargement of the posterior cingulate cortex provided moderately good support for the previous similar finding by Niu et al 69 As those authors pointed out, there is a higher prevalence of chronic posttraumatic headache in mild TBI than in moderate or severe TBI, which is surprising because most symptoms are less severe in mild TBI. Similarly, abnormal enlargement appears to occur more often in mild TBI, which is surprising because most volume abnormalities have been reported to occur less often in mild TBI.…”

“…Empirical evidence for this idea comes from a study of a group of patients with mild TBI, which found that abnormal enlargement of the anterior and posterior cingulate regions was associated with posttraumatic headache and a serum marker of neuroinflammation. 69 In a post hoc attempt to explore this possibility, we attempted to partially replicate their findings.…”