Post-traumatic headache (PTH) after mild traumatic brain injury (mTBI) is debilitating
and hard to diagnose. Unfortunately, PTH is highly prevalent in active duty personnel,
Veterans, as well as sport athletes. The high incidence and chronic nature of PTH
underscores the need to study these problems in animal models in order to develop
new and effective treatments. Patients suffering from PTH often present the same symptoms
as migraine patients, which can be studied in mice. We explored hypersensitivity to
a tactile stimulation of the periorbital facial and plantar paw areas in a model of
mTBI in mice using von Frey filaments. This mild closed head impact (mCHI) is induced
by a weight (30 g) dropped onto the intact skull once a day over 3 consecutive days,
after which mice develop a transient cephalic hypersensitivity between day 1 and day
5 after the injury, and then recover to normal thresholds. Additionally, after mice
recover from this transient cephalic hypersensitivity, an injection of normally non-noxious
triggers such as a low dose of calcitonin gene-related peptide (CGRP) or a low dose
of sodium nitroprusside (SNP, a nitric oxide donor) can induce tactile hypersensitivity.
This can last for at least 13 weeks after injury. Treatment with a CGRP-blocking monoclonal
antibody after injury, but prior to CGRP or SNP administration can alleviate this
sensitization. Preliminary data indicate that after injuries, administration of CGRP
is also able to induce light aversion at usually non-noxious dim light intensities.
In summary, we report that mice are primed by a mild TBI that sensitizes them to subsequent
migraine triggers in a CGRP-dependent manner. Dept. Defense W81XWH-16-1-0071, W81XWH-16-1-0211
to AFR; VA-ORD (RR&D) 1IO1RX002101 and C6810-C to AFR; IHA Research Award and Pilot
Grant from Iowa City VA Center for the Prevention and Treatment of Visual Loss to
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