Post-traumatic headache: epidemiology and pathophysiological insights

Ashina, Håkan; Porreca, Frank; Anderson, Trent; Amin, Faisal Mohammad; Ashina, Messoud; Schytz, Henrik Winther; Dodick, David W.

doi:10.1038/s41582-019-0243-8

Cited by 148 publications

(185 citation statements)

References 139 publications

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“…b)). However, a prolonged decrease in exploratory rearing activity was not noted at 3-14 days post the CHI (Time F(3,42) =2.8, p<0.05: Treatment F(1, 14) = 24.5, p<0.001; q<0.001,Figure 1(c)). In addition, head injured animals displayed an acute decrease in center zone exploration at 3 days post CHI ((Time F(3, 42) = 4.5, p<0.001: Treatment F(1, 14) = 4.7, p < 0.05; q<0.001;Figure 1(d)), suggesting elevated anxiety levels.…”

mentioning

confidence: 94%

“…Post-traumatic headache (PTH) is one of the most commonly occurring and disabling sequalae of traumatic head injury, in particular following motor vehicle accidents, falls and sport-related activities (1)(2)(3). PTH is defined by the International Classification of Headache Disorders (ICHD-3) as a secondary headache that develops within seven days after the head trauma, or regaining of consciousness following the injury to the head (4).…”

Section: Introductionmentioning

confidence: 99%

“…One of the key factors that is thought to influence the propensity to develop PTH is preexisting headache or migraine conditions (3). Yet, many cases of PTH arise de novo following a concussive head trauma (8).…”

Section: Introductionmentioning

confidence: 99%

“…An important factor that may influence the propensity to develop of PTH is the severity of the head trauma. PTH has been suggested to be more common after a mild trauma when compared to more severe events (3). However, moderate and severe traumas are also associated with high prevalence of PTH (12).…”

Section: Introductionmentioning

confidence: 99%

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Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model

Bree

Stratton²,

Levy

2020

Preprint

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Introduction: Posttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a traumatic head injury. The development of novel therapeutic approaches is nevertheless hampered by the paucity of preclinical models and poor understanding of the mechanisms underlying PTH. To address these shortcomings, we previously characterized the development of PTH-like pain behaviors in rats subjected to a single mild closed head injury using a 250 g weight drop. Here, we conducted a follow-up study to further develop this preclinical model by exploring the development of headache-like pain behaviors in male rats subjected to a single, but more severe head trauma (450 g) as well as following repetitive, subconcussive head impacts (150 g). In addition, we tested whether these behaviors involve peripheral CGRP signaling by testing the effect of systemic anti-CGRP monoclonal antibody (anti-CGRP mAb).Methods: Adult male Sprague Dawley rats (total n=138) were subjected to diffuse closed head injury using a weight-drop device, or a sham procedure. Three injury paradigms were employed: a single hit, using 450 g or 150 g weight drop, and three successive 150 g weight drop events conducted 72 hours apart. Changes in open field activity and development of headache-related cephalic and extracephalic mechanical pain hypersensitivity were assessed up to 42 days post head trauma. Treatment included systemic administration of a mouse anti-calcitonin-gene-related peptide monoclonal antibody (30 mg/kg.).Results: Rats subjected to 450 g closed head injury displayed an acute decrease in rearing and increased thigmotaxis, together with cephalic and extracephalic mechanical pain hypersensitivity that resolved by 6 weeks post-injury. Repetitive subconcussive head impacts using the 150 g weight drop, but not a single event, led to decreased vertical rearing as well as prolonged cephalic and extracephalic mechanical pain hypersensitivity. Early and prolonged anti-CGRP mAb treatment inhibited the development of the cephalic, but not extracephalic pain hypersensitivities in both the severe and repetitive subconcussive head impact models. Conclusions:When compared to the data obtained from male rats in the previous study, a more severe head injury gives rise to a prolonged state of cephalic and extracephalic hyperalgesia. Such enhanced headache-like behaviors also occur following repetitive, subconcussive head impacts.Extended headache-like behaviors following severe and repetitive mild closed head injury are ameliorated by early and prolonged anti-CGRP mAb treatment, suggesting a mechanism linked to peripheral CGRP signaling.

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confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model

Bree

Stratton²,

Levy

2020

Preprint

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“…The International Classification of Headache Disorders (ICHD) defines PTH as a secondary headache occurring within 7 days of TBI, or occurring upon regaining of consciousness after trauma [23]. PTH can be acute (resolved within 3 months of onset) or persistent [3], and also shares clinical characteristics of migraine [27; 28]. Despite its high prevalence, however, the pathophysiology of PTH is still poorly understood [3], due in large part to challenges in modeling this condition in animals.…”

Section: Introductionmentioning

confidence: 99%

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

Wattiez

Castonguay

Gaul

et al. 2020

Preprint

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Chronic complications of traumatic brain injury (TBI) represent one of the greatest financial burdens and sources of suffering in society today. A substantial number of these patients suffer from post-traumatic headache (PTH), which is typically associated with tactile allodynia.Unfortunately, this phenomenon has been under-studied, in large part due to the lack of wellcharacterized laboratory animal models. We have addressed this gap in the field by characterizing the tactile sensory profile of two non-penetrating models of PTH. We show that multifactorial TBI, consisting of aspects of impact, acceleration/deceleration, and blast wave exposure, produces long term tactile hypersensitivity and central sensitization, phenotypes reminiscent of PTH in patients, in both cephalic and extracephalic regions. By contrast, closed head injury induces only transient cephalic tactile hypersensitivity, with no extracephalic consequences. Both models show more severe phenotype with repetitive daily injury for three days, compared to either one or three successive injuries in a single day, providing new insight into patterns of injury that may place patients at greater risk of developing PTH. Importantly, even after recovery from transient cephalic tactile hypersensitivity, mice subjected to closed head injury had persistent hypersensitivity to established migraine triggers, including calcitonin gene-related peptide (CGRP) and sodium nitroprusside, a nitric oxide donor. Our results offer new tools for studying PTH, as well as preclinical support for a pathophysiologic role of CGRP in this condition. SummaryTwo models of post-traumatic headache after traumatic brain injury provide novel laboratory tools and insights in relative risks of injury and therapeutic opportunities.

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Association of Posttraumatic Headache With Symptom Burden After Concussion in Children

et al. 2023

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ImportanceHeadache is the most common symptom after pediatric concussion.ObjectivesTo examine whether posttraumatic headache phenotype is associated with symptom burden and quality of life 3 months after concussion.Design, Setting, and ParticipantsThis was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study, conducted September 2016 to July 2019 at 5 Pediatric Emergency Research Canada (PERC) network emergency departments. Children aged 8.0-16.99 years presenting with acute (&lt;48 hours) concussion or orthopedic injury (OI) were included. Data were analyzed from April to December 2022.ExposurePosttraumatic headache was classified as migraine or nonmigraine headache, or no headache, using modified International Classification of Headache Disorders, 3rd edition, diagnostic criteria based on self-reported symptoms collected within 10 days of injury.Main Outcomes and MeasuresSelf-reported postconcussion symptoms and quality-of-life were measured at 3 months after concussion using the validated Health and Behavior Inventory (HBI) and Pediatric Quality of Life Inventory–Version 4.0 (PedsQL-4.0). An initial multiple imputation approach was used to minimize potential biases due to missing data. Multivariable linear regression evaluated the association between headache phenotype and outcomes compared with the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score and other covariates and confounders. Reliable change analyses examined clinical significance of findings.ResultsOf 967 enrolled children, 928 (median [IQR] age, 12.2 [10.5 to 14.3] years; 383 [41.3%] female) were included in analyses. HBI total score (adjusted) was significantly higher for children with migraine than children without headache (estimated mean difference [EMD], 3.36; 95% CI, 1.13 to 5.60) and children with OI (EMD, 3.10; 95% CI, 0.75 to 6.62), but not children with nonmigraine headache (EMD, 1.93; 95% CI, −0.33 to 4.19). Children with migraine were more likely to report reliable increases in total symptoms (odds ratio [OR], 2.13; 95% CI, 1.02 to 4.45) and somatic symptoms (OR, 2.70; 95% CI, 1.29 to 5.68) than those without headache. PedsQL-4.0 subscale scores were significantly lower for children with migraine than those without headache only for physical functioning (EMD, −4.67; 95% CI, −7.86 to −1.48).Conclusions and RelevanceIn this cohort study of children with concussion or OI, those with posttraumatic migraine symptoms after concussion had higher symptom burden and lower quality of life 3 months after injury than those with nonmigraine headache. Children without posttraumatic headache reported the lowest symptom burden and highest quality of life, comparable with children with OI. Further research is warranted to determine effective treatment strategies that consider headache phenotype.

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Post-traumatic headache: epidemiology and pathophysiological insights

Cited by 148 publications

References 139 publications

Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model

Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

Association of Posttraumatic Headache With Symptom Burden After Concussion in Children

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