My research interest is the molecular basis of migraine. A hallmark of migraine is altered sensory perception coupled with debilitating pain. To understand the mechanisms underlying these events, we have focused on the neuropeptide calcitonin gene-related peptide (CGRP). CGRP levels are elevated during migraine and can induce migraine symptoms in people susceptible to migraine. Based on these clinical observations, we generated a CGRP-sensitized transgenic mouse as a preclinical model for testing pain and non-headache endpoints, such as light aversive behavior. We are currently identifying the cellular targets and mechanisms of CGRP action in the periphery and brain. 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 by cortical spreading depression, which is associated with the aura phase of migraine and occurs following traumatic brain injury (TBI). Because of the unexpectedly high frequency of migraine in Veterans with mild TBI, we initiated translational studies using two models of post-traumatic headache to test therapeutics, including CGRP-blocking antibodies. Our overall goals are to develop effective diagnostic and therapeutic strategies for migraine and post-traumatic headache.