BACKGROUND: According to the International Classification of Headache Disorders 3, post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) is a secondary headache reported to have developed within 7 days from head injury, regaining consciousness following the head injury, or discontinuation of medication(s) impairing the ability to sense or report headache following the head injury. It is one of the most common secondary headache disorders, and it is defined as persistent when it lasts more than 3 months. MAIN BODY: Currently, due to the high prevalence of this disorder, several preclinical studies have been conducted using different animal models of mild TBI to reproduce conditions that engender PTH. Despite representing a simplification of a complex disorder and displaying different limitations concerning the human condition, animal models are still a mainstay to study in vivo the mechanisms of PTH and have provided valuable insight into the pathophysiology and possible treatment strategies. Different models reproduce different types of trauma and have been ideated in order to ensure maximal proximity to the human condition and optimal experimental reproducibility. CONCLUSION: At present, despite its high prevalence, PTH is not entirely understood, and the differential contribution of pathophysiological mechanisms, also observed in other conditions like migraine, has to be clarified. Although facing limitations, animal models are needed to improve understanding of PTH. The knowledge of currently available models is necessary to all researchers who want to investigate PTH and contribute to unravel its mechanisms.

Campus Biomedico University Rome Italy

Child Neuropsychiatry Unit Department of PROMISE University of Palermo Palermo Italy

Department of Clinical and Molecular Medicine Sapienza University of Rome Rome Italy

Department of Human Neurosciences Sapienza University of Rome Rome Italy

Department of Neurology 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Neurology and Manual Medicine Pavlov 1st Saint Petersburg State Medical University Saint Petersburg Russia

Department of Neurology Headache Centre Charité Universitatsmedizin Berlin Berlin Germany

Department of neurology Kazaryan Clinic of Epileptology and Neurology Moscow Russia

Division of Vascular Medicine and Pharmacology Department of Internal Medicine Erasmus University Medical Center Dr Molewaterplein 50 3015 GE Rotterdam The Netherlands

Health Sciences Department University of Florence and Headache Centre Careggi University Hospital Florence Italy

Neurology Department Hospital Clínico Universitario of Valladolid Valladolid Spain

Neurology Department Hospital Universitari Vall d'Hebron Barcelona Spain

Pain Clinic Unit Department of Anesthesiology Pirogov City Clinical Hospital Moscow Russia

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