Date of Graduation

Summer 2015

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Paul Durham

Abstract

Approximately 2% of the US population is affected by chronic migraine (CM). CM is a recurring, neurological disorder characterized by painful headache, along with autonomic, gastrointestinal, and other somatic symptoms. Prolonged sensitization of the trigeminal system, which is implicated in CM, is comprised of peripheral primary trigeminal ganglion neurons that provide sensory innervation of the head and face and second order neurons in the spinal trigeminal nucleus (STN). The goal of my study was to evaluate anti-migraine drugs for their ability to inhibit ongoing peripheral and central sensitization of trigeminal nociceptors. An in vivo animal model was used to determine if two novel drugs in development and Topiramate, a common drug used to treat frequent migraine, could inhibit nocifensive responses to mechanical stimulation of trigeminal neurons. In addition, the trigeminal ganglion and STN were evaluated on a molecular level to determine if the drugs could inhibit expression of a signaling protein implicated in peripheral and central sensitization. My results provide evidence that the two novel drugs significantly inhibited nocifensive responses and decreased expression of Protein Kinase A (PKA) in the trigeminal ganglion and STN. In contrast, Topiramate did not decrease PKA expression and had no effect on nocifensive responses. Based on my findings, I conclude that these novel drugs may be beneficial in the treatment of CM.

Keywords

kinase, migraine, nociception, sensitization, trigeminal

Subject Categories

Biology

Copyright

© Shannon Nicole Stiles

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