Sensitisation of the trigeminovascular system : implications for migraine pathophysiology
Migraine is an episodic brain disorder characterised often by attacks of throbbing head pain and in many patients by sensitisation of the facial skin. Current research indicates that the dural blood vessels and their neural connectivity with the trigeminocervical complex play a fundamental role in the perception of these symptoms. As such, characterisation of this pathway may provide an insight into the pathological processes occurring during a migraine attack and offer new targets for the development of novel anti-migraine treatment strategies. Utilising the techniques of in vivo electrophysiology, intravital microscopy and c-fos immunohistochemistry, the studies in this thesis have explored the consequences of trigeminal primary afferent neuronal activation during the following conditions: Exposure to glyceryl trinitrate, a nitric oxide releasing compound, known to induce migraine in susceptible individuals. Peripheral sensitisation following application of various mediators to the dural and facial receptive field. Following "wind-up" stimuli, known to hyper-excite spinal neurons The findings from these studies demonstrate that the behaviour of second order neurons in the spinal trigeminal nucleus is fundamentally different following input from the dura mater compared to input from facial cutaneous afferents. Furthermore, the time course of sensitisation seen following application of prostaglandin E2 to the dural receptive field correlates well to the allodynia and hyperalgesia reported during migraine. Sensitisation of dural afferents may thus underlie at least part of the pathophysiology associated with migraine.