Arthritis is a chronic debilitating disease affecting millions of Canadians. Pain is a major symptom of arthritis and can be exacerbated during mechanical stimulation of the joint. In this project, we investigated whether changes occur in sensory neurotransmission in an animal model of monoarthritis and the neurochemicals that underlie such changes. Monoarthritis was induced by intra-articular injection of complete Freund's adjuvant (CFA) in the tibiotarsal joint of the rat. This model was characterised by a significant increase in ankle circumference and sensitivity to mechanical stimulus, as well as a decrease in ankle flexibility. Electrophysiological recordings from dorsal spinal cord neurones in intact animals demonstrated that the baseline activity of dorsal horn neurones was significantly higher in CFA-injected rats compared to vehicle-injected rats. Furthermore, the magnitude of the response of dorsal horn neurones to von Frey hair stimulation of the joint was significantly increased after CFA injection and was followed by a slowly decaying afterdischarge that was not present in control rats. Joint movement in arthritic rats caused an enhancement of the responses of wide dynamic range neurons to iontophoretic application of glutamate receptor agonists. This enhancement lasted 10--15 minutes and was blocked by pretreatment with the selective NK-1 receptor antagonist CP-96,345 (5mg/kg i.v.). These experiments suggest that joint movement in arthritic animals causes the release of substance P at central terminals within the dorsal spinal cord leading to a sensitisation of synaptic transmission. The enhancement of cellular excitability following an innocuous stimulus such as joint movement is at least partially mediated via activation of NK-1 receptors in the dorsal spinal cord and may underlie the exacerbation of the pain during arthritis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33069 |
| Date | January 2001 |
| Creators | Sharif, Reza N. |
| Contributors | Henry, James L. (advisor) |
| Publisher | McGill University |
| 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 | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Psychiatry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001838180, proquestno: MQ77061, Theses scanned by UMI/ProQuest. |
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