Migraine as well as other forms of vascular headache is among the most common of medical problems. Usually, it is associated with major changes in emotional and physiological functions. And it is the combination of the severe head pain and these changes that bring about suffering and impair the quality of life. In spite of the fact that pain that arises from deep structures (such as intracranial blood vessels) is generally of greater clinical importance than pain that arises from cutaneous organs (such as the skin), most pain research has focused on cutaneous pain. As a result, the neural basis of migraine, vascular headache and other head pains is poorly understood and highly controversial, and therefore not treated appropriately. Earlier studies suggested that migraine and vascular headache may be mediated through pain-sensitive fibers, branches of the trigeminal nerve, that innervate cranial blood vessels. However, because minimal information exists about the basic physiological properties of the craniovascular sensory pathway, understanding of it is extremely limited. To gain a better understanding of this sensory pathway we have recently identified peripheral (15 units) and central (10 units) trigeminal neurons that innervate the venous sinuses, recorded their responses to electrical, mechanical and chemical stimulation, monitored lasting changes in their activity, and mapped some of their axonal projections to higher brain regions. The proposed experiments will further our knowledge by investigating the physiological basis for the detection and transmission of nociceptive (painful) signals that originate in cranial blood vessels. In the first study we will continue to physiologically characterize athe primary afferent neurons that innervate the dura and sinuses by extracellularly recording from single neurons in the trigeminal ganglion. In the second study we will determine the effects of potentially sensitizing chemical stimuli on the spontaneous activity and sensitivity of these dura responsive primary afferent neurons by applying inflammatory mediators to the dura. In the third study we will continue to physiologically characterize the second order neurons in the trigeminal brainstem nuclei that innervate the dura and sinuses, determine the effects of inflammatory mediators on their activity, and identify their projection targets in the brain. In the fourth study we will identify areas of increased brain activity following noxious dural stimulation by measuring 2-deoxyglucose, c-fos and iodoantipyrine. These studies will provide information about the kinds of stimuli capable of activating athe craniovascular sensory pathway, the role of peripheral and central sensitization in maintaining vascular headache, which brain areas receive this craniovascular information directly, and which brain areas are involved in the processing of vascular head pain. Together, these studies are critical for further progress in understanding the neural basis of vascular head pain.

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Massachusetts General Hospital
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