Knight, Yolande Edna; (2002) Midbrain periaqueductal grey modulation of trigeminal nociception: Relationship to migraine. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Clinical evidence suggests that the midbrain periaqueductal grey (PAG) may play a major role in the headache component of migraine. Genetic studies indicate that migraine may be a calcium channelopathy, but it is unknown in which parts of the brain the channel dysfunction might occur. If affected by a channel dysfunction, such as the P/Q-type abnormalities in familial hemiplegic migraine, brainstem or midbrain regions that modulate nociception might be regions of dysfunction. Therefore, their study might offer insight into the basic neurobiology of migraine. Using the techniques of in vivo electrophysiology and fos immunohistochemistry in an experimental animal model of trigeminovascular nociception, the studies described in this thesis examine: i. The specific regions of the PAG which functionally modulate trigeminovascular nociception. ii. What effect the blockade of P/Q-type calcium channels in the PAG has on trigeminal nociceptive activity. iii. Which nuclei in the medulla and pons are involved in PAG modulation of trigeminovascular activity. The results demonstrate the ventrolateral region of the PAG (vlPAG) most specifically inhibits trigeminal nociception. The structures in the brainstem that comprise the nociceptive modulatory circuits and their associated autonomic components are involved to varying degree in integrating the modulation of and response to trigeminal nociception by the PAG. P/Q-type calcium channel blockade in the PAG facilitates trigeminal nociception. These studies support a role for the PAG in migraine headache and suggest a functional mechanism by which it could contribute to migraine pathophysiology.

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