Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.661329
Title: The contribution of AMPA receptors to neuropathic pain
Author: Rockett, M. P.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Abstract:
This study was designed to investigate the role of AMPA, NMDA, mGlu group I and VPAC2 receptors (Rs) in the generation of neuropathic pain. Firstly, the behavioural reflex responses of naïve rats to intrathecal administration of low doses of these receptor agonists, singly or in combinations were investigated. Combinations of two or more agonists caused increased behavioural responses to thermal and mechanical stimuli. The combination of AMPA with mGluR group I and VPAC2R agonists, showed a synergistic effect whereas other combinations were less then additive. Expression of AMPA receptor GluR1 and GluR2 subunits in the superficial dorsal horn was studied using confocal immunofluorescence. In the chronic constriction injury (CCI) model of neuropathic pain both the number of GluR1-immunpositive cell bodies and the level of GluR1 expression in cells decreased significantly in lamina II of the dorsal horn, ipsilateral to the injury. In contrast, there was no change in GluR2 expression or the degree of colocalisation of GluR1 and GluR2 receptor subtypes within individual cells following CCI. The subcellular distribution of GluR1 subunits was also noted to change significantly as a result of CCI. GluR1 subunits were found to redistribute distally into neuronal processes in lamina II cells ipsilateral to CCI and also in response to acute intrathecal AMPA treatment. This redistribution may reflect an increase in the number of GluR1-containing receptors associated with synaptic sites. The relationship between the presynpatic marker protein, bassoon and GluR1-immunopositive cells was investigated showing a significant increase in the number of bassoon immunopositive puncta associated with each GluR1-immunopositive cell ipsilateral to nerve injury. These results suggest that AMPA receptors are important in the central sensitisation underlying neuropathic pain. However, it is clear that several receptors are involved in triggering maximal behavioural responses, and potential therapeutic interventions may be more effective if designed to target more than one receptor type. There is also evidence to suggest that AMPA receptors may have differing roles dependent upon their subtype composition, so subtype-specific antagonists may potentially be useful in treatment of neuropathic pain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.661329  DOI: Not available
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