Frequent mild head injury promotes trigeminal sensitivity concomitant with microglial proliferation, astrocytosis, and increased neuropeptide levels in the trigeminal pain system.
BACKGROUND
Frequent mild head injuries or concussion along with the presence of headache may contribute to the persistence of concussion symptoms.


METHODS
In this study, the acute ﻿effects of recovery between mild head injuries and the frequency of injuries on a headache behavior, trigeminal allodynia, was assessed using von Frey testing up to one week after injury,﻿ while histopathological changes in the trigeminal pain pathway were evaluated using western blot, ELISA and immunohistochemistry. ﻿ RESULTS: A decreased recovery time combined with an increased mild closed head injury (CHI) frequency results in reduced trigeminal allodynia thresholds compared to controls. The repetitive CHI group with the highest injury frequency showed the greatest reduction in trigeminal thresholds along with greatest increased levels ﻿of calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis. Repetitive CHI resulted in astrogliosis in the central trigeminal system, increased GFAP protein levels in the sensory barrel cortex, and an increased number of microglia cells in the trigeminal nucleus caudalis.


CONCLUSIONS
Headache behavior in rats is dependent on the injury frequency and recovery interval between mild head injuries. A worsening of headache behavior after repetitive mild head injuries was concomitant with increases in CGRP levels, the presence of astrocytosis, and microglia proliferation in the central trigeminal pathway. Signaling between neurons and proliferating microglia in the trigeminal pain system may contribute to the initiation of acute headache after concussion or other traumatic brain injuries.
Department of Neurosurgery, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA, 19107, USA.
Ashley L
AL
Tyburski
Department of Neurosurgery, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA, 19107, USA.
Lan
L
Cheng
Temple University, Philadelphia, PA, USA.
Soroush
S
Assari
Temple University, Philadelphia, PA, USA.
Kurosh
K
Darvish
Department of Neurosurgery, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA, 19107, USA. Melanie.elliott@jefferson.edu.
Melanie B
MB
Elliott
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D006259:Craniocerebral Trauma / Q000150:complications*; D004195:Disease Models, Animal; D005911:Gliosis / Q000209:etiology*; D006261:Headache / Q000209:etiology* / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*; D020433:Trigeminal Nerve Diseases / Q000209:etiology* / Q000378:metabolism
D015740:Calcitonin Gene-Related Peptide
Astrocytosis; Calcitonin gene-related peptide; Concussion; Microglia; Migraine; Post-traumatic headache; Traumatic brain injury; Trigeminal