My research interest is the molecular basis of migraine. A hallmark of migraine is altered sensory perception coupled with head pain. To understand the mechanisms underlying these events, we have focused on the neuropeptide calcitonin gene-related peptide (CGRP), whose levels are elevated during migraine and can induce migraine symptoms in people susceptible to migraine. Based on these clinical observations, we generated CGRP-sensitized transgenic mice as preclinical models for testing non-headache endpoints, such as light aversive behavior and cutaneous hypersensitivity. In tandem, we are investigating potential causes of CGRP elevation in migraine. We have found that CGRP gene transcription is increased by positive feedback loops initiated by inflammatory signals and experimentally-induced cortical spreading depression, which is associated with the aura phase of migraine and occurs following traumatic brain injury (TBI). We have initiated translational studies to examine the unexpectedly high frequency of migraine symptoms in Veterans with mild TBI and are testing therapeutics using a preclinical model of post-traumatic headache. Towards that end, we are developing an automated grimace assay as a quantitative measure of non-evoked pain. Finally, we are initiating a collaboration with Dr. Iliff to merge his expertise with glymphatics and TBI with my lab’s expertise with CGRP and migraine to address the role of sleep in post-traumatic headache. Our overall goals are to develop effective diagnostic and therapeutic strategies for migraine and post-traumatic headache.