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Title: Electrophysiological studies on the pharmacology of the processing of inflammatory nociception in the rat
Author: Chapman, Victoria
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1994
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I have recorded the responses of nociceptive dorsal horn neurones to acute electrical and prolonged inflammatory stimuli in intact halothane anaesthetised rats. Dorsal horn neuronal responses to peripheral injection of formalin were biphasic: the first phase lasted from 0-10 minutes and the second from 10-60 minutes. Studies with peripheral local anaesthesia showed the second phase of the formalin response to be driven by afferent activity. Both phases of the formalin response were equally inhibited by intrathecal local anaesthetic. Peripherally, both phases of the formalin response were partly mediated by bradykinin acting at the B2 receptor, with prostaglandins contributing to the second phase only. Spinal B2 receptor antagonism reduced the second phase of the formalin response. Prostaglandins were shown to contribute to the spinal processing of both phases of the response. The AMPA but not the NMDA receptor for the excitatory amino-acids plus the neurokinin-1 receptor were shown to be involved in the spinal processing of the first phase. NMDA mediated wind up and NK1 receptor activation contributed to the second phase of the formalin response. Intrathecal administration of somatostatin and the analogue, sandostatin, did not influence acute nociceptive responses but inhibited the formalin response. Intrathecal morphine inhibited both the acute nociceptive responses and the formalin response. Multiple peripheral and central transmitters therefore contribute to the full manifestation of the formalin response. The responses of spinal neurones after ultraviolet irradiation of the hindpaw were studied and compared to controls. The dorsal horn neurones now exhibited spontaneous activity and whereas the C-fibre related responses were unaltered the Aβ-fibre responses were enhanced above the control. Drug effects were not different from control animals except that Aβ-fibre evoked responses were inhibited by NMDA receptor antagonism and wind up of the neurones was inhibited by B2 receptor antagonism. The aim of these studies was to investigate the peripheral and spinal pharmacology of nociceptive transmission in different animal models of pain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available