Abstract

Migraine is a common, episodic neurological disorder that includes headache, nausea and hypersensitivity to sensory stimuli. During the headache phase of migraine, migraine patients can be especially hypersensitive to thermal stimuli. The unpredictable and episodic nature of migraine makes it difficult to treat and much of the mechanism of migraine has yet to be elucidated. A T44A substitution in casein kinase 1δ is inherited with migraine with aura. A transgenic mouse model suggests that animals with this mutation exhibit increased sensitivity to thermal stimuli after injection with nitroglycerin (NTG). We performed behavior assays that measure animal responses to thermal stimuli, after injection with NTG, a known migraine-inducer in human migraine patients. Female animals with the CK1δ-T44A mutation are more sensitive than wildtype littermates, suggesting a sex difference emerges in pain sensitivity in animals that express the CK1δ-T44A but not in wildtype siblings. Female CK1δ-T44A animals are more sensitive to the effects of NTG on pain than male CK1δ-T44A mice. This indicates a potential sex hormone related pain response. Since estrogen is implicated in both migraine and pain response, we test the thermal sensitivity of heterozygous ERβKO/+ and CK1δ-T44A; ERβKO/+ mice compared to wildtype and CK1δ-T44A mice. Overall thermal sensitivity is decreased before stress of injection in both male and female ERβKO/+ and CK1δ-T44A: ERβKO/+ mice. This demonstrates that ERβ is necessary for thermal nociception in untreated mice. However, after injection with saline or NTG, animals of all genotypes responded to thermal stimuli similarly. This suggests that estrogen signaling through ERβ is likely not part of the pathway of NTG-induced thermal sensitivity or that one copy of ERβ is sufficient for NTG-induced thermal sensitivity. Since ERβ is fully functional in CK1δ-T44A mice and CK1δ-T44A mice have wildtype thermal sensitivity at baseline, we can conclude that CK1δ-T44A does not modulate ERβ to affect thermal sensitivity in untreated animals.

Degree

College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry

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