COCHLEAR BLOOD FLOW AND NEUROPEPTIDES

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The migraine related inner ear symptoms for phonopobia , tinnitus, hearing fluctuation, hearing loss, and increased noise sensitivity provide evidence for a possible neurological substrate connecting basilar artery migraine and cochlear pathophysiological mechanisms. Recently we have identified a previously unreported sensory innervation of the cochlear blood vessels originating from the trigeminal ganglia. We have shown that this sensory innervation has a significant effect on cochlear blood flow (CBF) in both normal and pathological conditions (e.g., in the animal model of endolymphatic hydrops, one of the symptoms of Meniere's disease). This proposal seeks to further define the anatomical basis and mechanisms of the trigemino-sensory network around the vertebrovasilar and cochlear vascular system. The proposal offers the hypothesis that the trigemino-sensory system and its related neuropeptide system are important factors contributing to basilar migraine and vascular homeostasis of the cochlea. The study has three specific aims. Aim 1. To establish if there is a physiological basis for the cochlear symptoms in basilar artery migraine headache. Positive results will confirm a common functional basis for basilar migraine and cochlear symptoms, the basis could be neurogenic inflammation. Aim 2. To demonstrate if vanilloid receptor (VR1) and substance P (SP) are co-localized around cochlear blood vessels, the basilar artery and its related branches. Positive immunocytochemical results will demonstrate: (a) network of the VR1 and (b) SP co-labeled primary sensory neurons around the basilar artery; anterior inferior cerebellar artery (AICA), spiral modiolar artery (SMA) and radial artery; (c), Capsaicin will cause a significant reduction in the density of labeled sensory fibers. Aim 3. To determine the vasoregulatory disturbance of the trigemino-sensory neurons in endolymphatic hydrops. In this study positive results will demonstrate that endolymphatic hydrops causes a reduction in the stimulated trigeminal ganglion induced CBF change. The studies of the proposal will help clarify how trigemino-sensory neurons regulate the vertebro-basilar vascular system and cochlear fluid balance under normal and pathological conditions.