Persistent post-traumatic headache: a migrainous loop or not? The preclinical evidence

Abstract

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.

Prevalence of post-traumatic stress disorder in the United States: a systematic literature review

“…Individuals with PTSD may recurrently experience memories, sensations, and emotions of a traumatic event through sensory flashbacks or nightmares, or experience avoidance, irritability, hypervigilance, difficulty sleeping, poor concentration, or emotional withdrawal 3 . Additionally, PTSD is associated with higher risk of suicide and suicidal ideation [4][5][6] , as well as other negative clinical outcomes such as persistent post-traumatic headache [7][8][9] and disrupted sensory filtering 10,11 . In the United States (US), it is estimated that over 80% of the population will be exposed to a traumatic event at some point 12 , and that over 8% of those exposed will subsequently develop PTSD 13 .…”

Position Paper on Post-Traumatic Headache: The Relationship Between Head Trauma, Stress Disorder, and Migraine

“…The debate on the relationship between mTBI, migraine, PTH, and PTSD has not yet found a definitive position [79,80]. It is unclear whether a head trauma triggers a biologically unique headache condition or whether the head pain mechanisms share migraine or tension-type pathways.…”

“…Using the same methodology, also peripheral (hind paw) hypersensitivity, which represents a marker of extra-cephalic allodynia, reflecting central sensitization at a level higher than the trigeminal system, may be assessed. However, this symptom is not consistently observed in studies of migraine or post-traumatic headache, complicating its translational interpretation [49]. Besides allodynia, behavioural tests may include the study of spontaneous locomotor and exploratory activity and recognition memory, as well as the avoidance of locations where a trigger was previously administered.…”

“…Besides allodynia, behavioural tests may include the study of spontaneous locomotor and exploratory activity and recognition memory, as well as the avoidance of locations where a trigger was previously administered. Besides the initial injury, administration of glyceryl trinitrate or bright light stress has been used to study susceptibility to headache triggers after previous brain injury [49]. Unfortunately, studies have not attempted to investigate activation of the trigeminal system by means of cellular recordings that could more accurately assess the onset of sensitization.…”

Models for Treating Post-traumatic Headache

“…Or, is it a completely separate headache disorder with overlapping symptomatology? Important studies are working to tackle this dilemma, including preclinical models [22] as well as clinical investigations utilizing imaging studies [23] and detailed phenotypic analysis of PTH [24].…”