Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles
Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles
Abstract 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 well-characterized 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.
Wattiez A-S.、Waite J.S.、Reis A.、Sowers L.P.、Russo A.F.、Cintr¨?n-P¨|rez C.J.、V¨￠zquez-Rosa E.、Gaul O.J.、Rea B.J.、Pieper A.A.、Schmidt C.M.、Castonguay W.C.
Department of Molecular Physiology and Biophysics, University of Iowa||Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health CenterDepartment of Molecular Physiology and Biophysics, University of IowaDepartment of Molecular Physiology and Biophysics, University of IowaCenter for the Prevention and Treatment of Visual Loss, Veterans Administration Health CenterDepartment of Molecular Physiology and Biophysics, University of Iowa||Department of Neurology, University of Iowa||Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health CenterHarrington Discovery Institute, University Hospitals Cleveland Medical Center||Department of Psychiatry, Case Western Reserve University||Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center||Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve UniversityHarrington Discovery Institute, University Hospitals Cleveland Medical Center||Department of Psychiatry, Case Western Reserve University||Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center||Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve UniversityDepartment of Molecular Physiology and Biophysics, University of IowaDepartment of Molecular Physiology and Biophysics, University of Iowa||Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health CenterHarrington Discovery Institute, University Hospitals Cleveland Medical Center||Department of Psychiatry, Case Western Reserve University||Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center||Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University||Weill Cornell Autism Research Program, Weill Cornell Medicine of Cornell University||Department of Neuroscience, Case Western Reserve University, School of MedicineDepartment of Molecular Physiology and Biophysics, University of IowaDepartment of Molecular Physiology and Biophysics, University of Iowa||Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health Center
神经病学、精神病学医学研究方法基础医学
Wattiez A-S.,Waite J.S.,Reis A.,Sowers L.P.,Russo A.F.,Cintr¨?n-P¨|rez C.J.,V¨￠zquez-Rosa E.,Gaul O.J.,Rea B.J.,Pieper A.A.,Schmidt C.M.,Castonguay W.C..Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles[EB/OL].(2025-03-28)[2025-08-14].https://www.biorxiv.org/content/10.1101/2020.06.01.127944.点此复制
评论