CGRP-induced migraine-like headache in persistent post-traumatic headache attributed to mild traumatic brain injury.

OBJECTIVE: To ascertain whether intravenous infusion of calcitonin gene-related peptide (CGRP) can induce migraine-like headache in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) and no pre-existing migraine. METHODS: A non-randomized, single-arm, open-label study at a single site in Denmark. Eligible participants were aged 18 to 65 years and had a known history of persistent post-traumatic headache attributed to mild TBI for ≥ 12 months. All participants received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min. A headache diary was used to collect outcome data until 12 h after the start of CGRP infusion. The primary end point was the incidence of migraine-like headache during 12-hour observational period. RESULTS: A total of 60 participants completed the study protocol and provided data for the analysis of the primary end point. The median age was 32.5 (IQR, 25.5-43.0) years; 43 participants (72%) were female. Following CGRP infusion, 43 (72%) of 60 participants developed migraine-like headache during the 12-hour observational period. The median time to peak headache intensity was 40 min (IQR, 20-60), and the median peak headache intensity was 6 (IQR, 5-8) on the 11-point numeric rating scale. CONCLUSION: Intravenous infusion of CGRP is a potent inducer of migraine-like headache in people with persistent post-traumatic headache attributed to mild TBI. This observation underscores the importance of CGRP in the genesis of migraine-like headache that is often experienced by individuals who are afflicted by persistent post-traumatic headache. Further research is warranted to ascertain whether other signaling molecules also contribute to the disease mechanisms underlying post-traumatic headache.

Risk Factors for the Development of Post-Traumatic Headache Attributed to Traumatic Brain Injury: A Systematic Review.

OBJECTIVE: To systematically identify risk factors for the development of post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) as defined in the International Classification of Headache Disorders (ICHD). BACKGROUND: PTH is a common sequela of TBI and a leading cause of injury-related disability worldwide. However, little is known about risk factors for the development of PTH attributed to TBI. METHODS: We searched PubMed and Embase for literature on risk factors for the development of acute and/or persistent PTH attributed to TBI in accordance with any version of the ICHD. Original studies published in English and of prospective, cross-sectional or retrospective design were considered for the review. Data extraction was performed independently by 2 investigators. RESULTS: Of 1993 potentially relevant articles identified, 3 articles met the inclusion criteria. The following risk factors were assessed for the development of acute PTH: age, sex, type of injury, loss of consciousness, previous TBIs, history of primary headache disorders, history of chronic pain condition other than headache, current treatment for depression/anxiety, attention or learning disorders, body mass index, and other diseases (not further specified). None of the included studies assessed risk factors for the development of persistent PTH. CONCLUSIONS: We found that there is little evidence for any risk factors involved in the development of acute PTH, whereas no study had assessed risk factors for the development of persistent PTH. Further studies are warranted and should be powered to examine possible risk factors for the development of PTH. Rigorous methodology and standardized monitoring should be prioritized to support high-quality research and validate potential findings.