Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419479
Title: Trigeminovascular nociceptive neurotransmission : a microiontophoretic study
Author: Shields, Kevin Gerald
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2005
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Abstract:
Migraine is a common and disabling condition, affecting up to 15% of the population. This thesis sought to characterise certain aspects of the pharmacology of trigeminovascular nociceptive neurotransmission in neurons of the trigeminocervical complex (TCC) in the cat and also the rat ventroposteromedial thalamic nucleus (VPM). Electrical stimulation of the superior sagittal sinus (SSS) combined with the microiontophoretic ejection of L-glutamate were used to locate the cell bodies of neurons activated by trigeminovascular nociceptive input in the two regions. Agents were then microiontophoretically ejected onto these neurons to study their modulation of action potential firing. To investigate a potential role for the thalamus in migraine, commonly used antimigraine agents were microiontophoresed onto thalamocortical neurons within the VPM nucleus. Sodium valproate reversibly inhibited the response to SSS stimulation and L-glutamate ejection. The effects of GABA were also studied and found to have a similar action to valproate on trigeminovascular nociception. This appeared to involve activation of both GABAA and GABAB receptors. Naratriptan (a typical second generation triptan) similarly inhibited both responses. In addition to its action on serotonin 5-HT1B/1D receptors, this inhibition was also mediated by activation of 5- HT1B/1D receptors. Ergometrine maleate had a similar effect to naratriptan. Propranolol (a beta blocker) reversibly inhibited the response to SSS stimulation and L-glutamate ejection. This appeared to be through blockade of beta adrenoceptors as it could be antagonised by co-ejection of isoproterenol. The selective beta1 antagonist atenolol had a similar action to propranolol while beta2 and beta3 antagonists were ineffective. These results suggest that neurons in the VPM may be a target for anti-migraine medications and a fruitful subject for further research. The role of high threshold voltage gated calcium channels (VDCC) in trigeminovascular nociceptive neurotransmission by second order neurons of the TCC was also studied. The effects of selective peptide blockers of L-, N-, and P/Q-type VDCCs were examined. Microiontophoretic ejection of Agatoxin IVa/TK (P/Q-), co-conotoxin GVIa (L-) and calciseptine (N-type) reversibly inhibited neuronal firing in response to L-glutamate. This indicates an important post-synaptic role for VDCCs in regulating nociceptive neurotransmission within the TCC.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.419479  DOI: Not available
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