PERIPHERAL ACTIONS OF CGRP IN MIGRAINE-LIKE BEHAVIOR

Migraine is a neurological disorder that presents as a headache lasting 4-72 hours with aggravation by movement and involves sensory alterations, including photophobia. Although migraines are not a new topic in medicine, diagnosing and treating migraines has proven difficult. Relevant to migraine, calcitonin gene-related peptide (CGRP) is a neuropeptide highly implicated in its pathophysiology with CGRP receptors present in the trigeminovascular system on approximately 50% of neurons. We have previously shown that peripheral CGRP can cause light aversion, a surrogate to photophobia experienced by ~90% of migraineurs. To establish a link between pain and light aversion, we wanted to determine if 1) the light aversive phenotype induced by peripheral CGRP can be alleviated by the anti-migraine drug sumatriptan and 2) if facial discomfort induced by peripheral injection of CGRP can be attenuated by anti-migraine drug sumatriptan. In this study, we first showed that sumatriptan can block light aversive behavior in mice. In the next study, while the lab had previously showed that CGRP causes facial discomfort, under my conditions, we were not able to confirm CGRP causes a squint (discomfort) response. With a power analysis we were able to conclude that a larger sample size (n=12) and an increase in measurement time points for each mouse (n=6) would be needed. Also, a dark to light condition would be preferable to the light to dark condition conducted in this experiment. In conclusion, the ability of sumatriptan to block light aversion in mice supports the conclusion that CGRP can induce migraine-like symptom in mice. Further experiments will be needed to test whether the same conclusion can be applied to CFRP-induced facial discomfort in mice.