Holmes Scott A, Mar'i Joud, Lemme Jordan, Maallo Anne Margarette, Lebel Alyssa, Simons Laura, O'Brien Michael J, Zurakowski David, Burnstein Rami, Borsook David
Department of Anesthesia, Critical Care and Pain Medicine, Pediatric Pain Pathway Lab 1, Boston, MA 02215, USA.
Pain and Affective Neuroscience Center, Boston Children's Hospital, Boston, MA 02215, USA.
Children (Basel). 2022 Dec 26;10(1):45. doi: 10.3390/children10010045.
Physical insult from a mild Traumatic Brain Injury (mTBI) leads to changes in blood flow in the brain and measurable changes in white matter, suggesting a physiological basis for chronic symptom presentation. Post-traumatic headache (PTH) is frequently reported by persons after an mTBI that may persist beyond the acute period (>3 months). It remains unclear whether ongoing inflammation may contribute to the clinical trajectory of PTH. We recruited a cohort of pediatric subjects with PTH who had an acute or a persistent clinical trajectory, each around the 3-month post-injury time point, as well as a group of age and sex-matched healthy controls. We collected salivary markers of mRNA expression as well as brain imaging and psychological testing. The persistent PTH group showed the highest levels of psychological burden and pain symptom reporting. Our data suggest that the acute and persistent PTH cohort had elevated levels of complement factors relative to healthy controls. The greatest change in mRNA expression was found in the acute-PTH cohort wherein the complement cascade and markers of vascular health showed a prominent role for C1Q in PTH pathophysiology. These findings (1) underscore a prolonged engagement of what is normally a healthy response and (2) show that a persistent PTH symptom trajectory may parallel a poorly regulated inflammatory response.
轻度创伤性脑损伤（mTBI）造成的身体损伤会导致大脑血流变化以及白质出现可测量的变化，这表明慢性症状表现存在生理基础。创伤后头痛（PTH）在mTBI患者中经常出现，可能会持续超过急性期（>3个月）。目前尚不清楚持续的炎症是否会影响PTH的临床病程。我们招募了一组患有PTH的儿科受试者，他们的临床病程为急性或持续性，每个受试者在受伤后约3个月的时间点，同时还招募了一组年龄和性别匹配的健康对照。我们收集了唾液中mRNA表达标志物以及脑成像和心理测试数据。持续性PTH组表现出最高水平的心理负担和疼痛症状报告。我们的数据表明，相对于健康对照，急性和持续性PTH队列中的补体因子水平升高。在急性PTH队列中发现mRNA表达变化最大，其中补体级联反应和血管健康标志物显示C1Q在PTH病理生理学中起重要作用。这些发现（1）强调了正常健康反应的长期参与，（2）表明持续性PTH症状轨迹可能与炎症反应调节不良平行。
