• Håkan Ashina, Afrim Iljazi, Haidar M Al-Khazali, Thien Phu Do, Anna K Eigenbrodt, Eigil L Larsen, Amalie M Andersen, Kevin J Hansen, Karoline B Bräuner, Basit Ali Chaudhry, Casper E Christensen, AminFaisal MohammadFMDanish Headache Center, Department of Neurology, Faculty of Health and Medical Sciences, Rigshospitalet - Glostrup, University of Copenhagen, Copenhagen, Denmark.Department of Neurorehabilitation / Traumatic Brain Injury, Rigshospital, and Henrik W Schytz.
• Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
• J Headache Pain. 2022 Oct 17; 23 (1): 135.

ObjectiveTo 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.MethodsA 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.ResultsA 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.ConclusionIntravenous 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.© 2022. The Author(s).

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