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Title: Pharmacological studies of bradykinin and other inflammatory mediators in rat neural preparations
Author: Asghar, Aziz-Ur-Rehman
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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This thesis tests the hypothesis that certain mediators (purines, catecholamines and bradykinin), which are known to be involved in inflammation, contribute to the sensitisation of peripheral nociceptors that occurs in chronic inflammation and hyperalgesia associated with arthritis. The major part of the studies determined the role of these substances and their pharmacological receptors in modulating discharge recorded from high threshold C-fibre mechanonociceptors (on-going or 'spontaneous', and mechanically-evoked) in normal ankle joints and in those with a monoarthritis induced by Freunds complete adjuvant (FCA). Some of the in-vitro neuropharmacological investigations were complemented by behavioural studies on intact normal and arthritic rats. Related in vitro experiments were performed involving a) extracellular 'grease gap' recordings from various peripheral nerves and b) contractile responses of the electrically-stimulated rat vas deferens. Recordings from C-fibres in arthritic joints revealed an enhanced resting discharge, a greater number of receptive fields and lower mechanical activation thresholds (sensitisation) of mechanonociceptors as compared to untreated joints. Indomethacin significantly attenuated, but did not abolish, either the elevated resting discharges recorded from C-fibres in arthritic joints or the swelling, mechanical hyperalgesia and inflammation associated with functional studies in monoarthric rats. The results show that C-fibre afferent discharge from articular mechanonociceptors in the normal and chronically-inflamed (adjuvant-arthritic) rat ankle joint is modulated by bradykinin (excitation and sensitisation). Catecholamines can also cause excitation and sensitisation of arthritic joints, but purines appear to have no effect on the activity of these sensory receptors. Bradykinin, acting via bradykinin B2 receptors plays an important role in altering neural excitability in the rat, and different subtypes of B2 receptor may be involved. Overall, the present results add further to our knowledge and understanding of the peripheral mechanisms involved in nociception in the normal state and in chronic inflammation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available