Date of Graduation

Fall 2012

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Paul Durham

Keywords

trigeminal nerve, nociception, pain, orexin, orexin receptor antagonist

Subject Categories

Biology

Abstract

Migraine is a prevalent neurovascular disorder that causes throbbing pain and disruptions in sensory perception. This disorder is mediated by the trigeminal nerve, which provides sensory innervation to the face, scalp, and meninges. Migraine pain is conveyed to the brain via the trigeminothalamic tract, which relays nociceptive signaling from primary nociceptors to the hypothalamus. Orexins are excitatory, hypothalamic neuropeptides implicated in pain pathways, as well as regulation of sleep and hunger. More specifically, orexins are involved in trigeminal nerve transmission of migraine pain by modulating neuronal membrane excitability. There are two orexin receptors that differentially bind orexin peptides. Single and dual orexin receptor antagonists have been synthesized to selectively block the activity of these orexinergic receptors. I hypothesized that a single orexin receptor antagonist blocking orexin receptor 2 would have the same inhibitory effect as a dual orexin receptor antagonist in a rat inflammatory model of acute migraine. To test my hypothesis, I determined the ability of each antagonist to suppress levels of inflammatory cytokines in the trigeminal ganglia and spinal trigeminal nucleus. Based on my results, I found that a single orexin receptor antagonist that blocks only orexin receptor 2 is equally as effective as a dual orexin receptor antagonist at suppressing inflammatory cytokines in the trigeminal ganglion and spinal trigeminal nucleus.

Copyright

© Kelly Eileen Crowe

Campus Only

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