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Title: The role of kinins in inflammatory pain and their modulation by other inflammatory mediators
Author: Kelly, David C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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This thesis tests the hypothesis that certain inflammatory mediators, including kinins and cytokines are involved in sensitisation of peripheral nociceptors and contribute the hyperalgesia associated with inflammatory conditions. These studies involved the development of a new model for recording from C-fibres innervating the rat knee joint and determined the role of these substances and their interactions in modulating neural discharge from articular nociceptors. Complementary behavioural studies were carried out to assess the role of these mediators in thermal and mechanical hyperalgesia. Recordings from C-fibres innervating the medial side of the rat knee joint revealed that Bk induced an increase in neural discharge in normal and arthritic knee joints which was blocked by a kinin B2 receptor antagonist. icatibant. desArg9-Bk was ineffective in normal joints, however in arthritic joints desArg9-Bk induced an increase in neural discharge in C-fibres which was mediated via kinin B1 receptors, as it was reduced by desArg9leu8-Bk. but not icatibant. The results illustrate a role for both kinin B2 and B1 receptors in modulating neural discharge from knee joint C-fibres and hyperalgesia in inflammation. IL-1β is involved in modulating neural discharge from articular C-fibres and modulation of kinin-mediated modulation of neural discharge which appears to involve generation of prostanoids in the case of enhancement of Bk-mediated responses. These results also highlight a role for IL-4, IL-10 and nitric oxide as mediators which potentially limit the hyperalgesia associated with inflammation. Overall, the present results add further to our knowledge and understanding of the peripheral mechanisms involved in inflammatory pain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available