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Title: The role of some putative mediators of peripheral nociceptor activation in adjuvant-induced experimental arthritis
Author: Gauldie, Stephan D.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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In this thesis behavioural and electrophysiological techniques in both the rat and the mouse were used to determine the effect of a number of mediators and/or pharmacological receptors reported to be involved in chronic inflammation and nociception. The specific aims of the thesis centred on testing the following hypotheses: a) The neuropeptide somatostatin inhibits sensory nerve function in both normal and arthritic knee joints, b) the endocannabinoid anandamide activates peripheral nociceptors via its reported action at the vanilloid receptor (VR1), c) chronic unilateral inflammation of the knee joint can be induced in mice using Freund’s Complete Adjuvant (FCA), and d), the purinoceptor P2X7 plays a role in the induction of inflammation and hyperalgesia associated with experimental arthritis in mice. An additional aim of the thesis was in vivo neural recording from nociceptors innervating the mouse knee joint with a view to examining transgenic mice in future studies. In summary, in relation to the hypothesis being tested, the results showed that: a) the reported anti-nociceptive effect of somatostatin is not mediated by action on peripheral nociceptors or the inhibition of tested algogens, b) anandamide is able to directly activate sensory afferents via VR1 receptors, c) chronic, unilateral arthritis can be induced in mice by repeated intra-articular injections of FCA, and d P2X7 purinoceptors do not play a role in the induction of inflammation and hyperalgesia associated with the FCA model of unilateral arthritis. Innovation in this thesis included a novel model of murine unilateral arthritis and the development of a new technique for direct measurement of evoked discharge from peripheral nociceptors innervating the mouse knee joint. These advances in knowledge provide information relevant to understanding inflammatory joint disease and for future drug development.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available