This thesis examined the effects of long-term inhibition of excitatory amino acid transporter 2 (EAAT2) on the excitability of dorsal horn neurons in defined-medium organotypic slice cultures (DMOTCs). Previous reports suggest that inhibition of EAAT2 may be involved in development of neuropathic pain induced by brain-derived neurotrophic factor (BDNF). Experiments were carried out using confocal Ca2+ imaging to assess the excitability of dorsal horn neurons.
Long-term treatment with EAAT2 blocker, dihydrokainate (DHK), prominently increased the neuronal excitability. Long-term exposure to DHK had a significant effect on NMDA, AMPA and metabotropic glutamate subtype 1 (mGluR1) receptors. Lastly, long-term treatment with BDNF and DHK increased activity of AMPA receptors but only DHK significantly increased activity of NMDA receptors. These findings suggest inhibition of EAAT2 and BDNF may have different pathways to promote neuropathic pain and modulating the activity of EAAT2 may be a novel therapeutic approach for neuropathic pain.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1619 |
| Date | 06 1900 |
| Creators | Kim, Helena J |
| Contributors | Smith, Peter A (Pharmacology), Ballanyi, Klaus (Physiology), Kerr, Bradley J (Anesthesiology and Pain Medicine) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 2676070 bytes, application/pdf |
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