Effects of Single and Dual Orexin Receptor Antagonists on Trigeminal Nociception

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.

Name thesis:degree_name

Master of Science in Biology

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Biology

Year

2012

Author dc:creator

• Crowe, Kelly Eileen

Contributors dc:contributor

• Paul Durham

• trigeminal nerve
• nociception
• pain
• orexin
• orexin receptor antagonist
• Biology

Statement dc:rights

• © Kelly Eileen Crowe

Repository record dc:identifier

https://bearworks.missouristate.edu/theses/1307

OAI identifier oai:identifier

oai:bearworks.missouristate.edu:theses-2308