Phenotype-guided Management of Post-traumatic Headache: An Update on Pathophysiology and Treatment

To provide an update on the pathophysiology, phenotyping, and management of post-traumatic headache (PTH) following mild traumatic brain injury (mTBI), and to propose a phenotype-guided framework for evaluation and treatment.

Emerging evidence suggests that PTH represents a distinct pathophysiological entity rather than simply a variant of migraine. Recent studies involving calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), autonomic dysfunction, and neuroimaging biomarkers suggest that PTH may comprise several biologically distinct subgroups rather than a single disorder. Current management increasingly emphasizes phenotype-guided treatment and multidisciplinary rehabilitation interventions. However, PTH-specific randomized trial data remain limited, and most treatment recommendations continue to be extrapolated from primary headache disorders. PTH is heterogeneous, with overlapping clinical phenotypes. Management should be individualized based on headache phenotype and patient comorbidities. Given the multifactorial pathophysiology of PTH, a multimodal approach is recommended, integrating phenotype-guided pharmacologic therapy, targeted rehabilitation, and behavioral and lifestyle interventions.