Document Type

Poster

Publication Date

4-2-2014

Comments

Sigma XI 2014 conference

Abstract

Introduction

Headache is a highly prevalent symptom in all severities of traumatic brain injury (TBI), and it is one of the most common symptoms of post-traumatic headache. Post-traumatic headache (PTH) remains the most common chronic pain syndrome within the TBI patient population1. Mild and moderate forms of TBI are more prevalent than severe forms, but it is currently believed that PTH occurrence is not related to the severity of TBI1. Despite being a common symptom following injury, little is known about the pathogenesis of post-traumatic headache. This is partly due to a lack in preclinical animal models studying PTH1. A large proportion of mild head injuries are blunt head traumas (i.e., closed head injury) caused by vehicular crashes, falls, sports or recreation activities, and military training regardless of deployment setting. Mild TBI (mTBI) can be a diffuse injury (closed head injury or concussion) or a focal-diffuse injury (e.g. blunt trauma with a lesion).

In many patients, PTH resolves within 3 months of injury; however, in others it can continue for much longer1. The International Classification of Headache Disorders defines PTH as headache secondary to head trauma developing within seven days of injury1. Headache pain involves abnormal activation of the trigeminovascular system1. This can cause the release of calcitonin gene-related peptide (CGRP), a neuropeptide with a known role in migraine2,3. CGRP was also shown to play a role in PTH1. CGRP is released in the trigeminal pain pathway by the trigeminal ganglia of cranial nerve V. The release of CGRP has been shown to increase inducible nitric oxide synthase (iNOS) release from trigeminal ganglia glial cells, and a reciprocal relationship between the two is said to exist3,4. The release of iNOS can cause the excessive release of nitric oxide (NO), a damaging free radical. Increases in CGRP have been reversed with sumatriptan4, as well as other drugs. Previously, our lab has shown an increase in CGRP in the caudal brainstem after a focal TBI, indicating sensitization of the trigeminal ganglia neurons. The objective of this study was to determine the role of CGRP in iNOS production by employing pharmacological blockade. This study determined the effects of a 5-HT1 receptor agonist (sumatriptan) and a CGRP antagonist (MK8825) on levels of iNOS as these drugs inhibit CGRP release and binding, respectively, on iNOS levels in the ganglia and trigeminal nucleus caudalis.

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