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Title: The role of tachykinins in acute nociceptive responses and in long term changes within spinal neurons during inflammation
Author: Parker, Rachel
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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The tachykinins, substance P (SP) and neurokinin A (NKA), contained in primary afferent fibres, are thought to function as nociceptive neurotransmitters in the spinal cord. This study addressed the role of their receptors (NK1 and NK2. respectively) in mediating responses of lamina I dorsal horn neurons, using selective agonists and antagonists in a number of different approaches. A proportion of lamina I cells may receive direct monosynaptic contacts from small diameter primary afferents, respond to nociceptive stimuli and are believed to undergo prolonged changes in responsiveness and receptive field properties along with altered genomic expression, including increased expression of preprodynorphin (PPD) mRNA during sustained noxious activation, such as occurs in peripheral inflammation. Knowledge of the mechanism of such central sensitisation could provide a highly selective treatment for the severe clinical problems of inflammation and perhaps neuropathic pain. Studies were carried out in α-chloralose/urethane anaesthetised rats. The effects of ionophoretic application of tachykinin receptor agonists on the responses of single lamina I nociceptive neurons to brief noxious cutaneous stimulation were investigated by extracellular recording. The endogenous NK2 receptor agonist, NKA and a highly-selective NK2 receptor agonist, GR 64349 markedly, but transiently facilitated the spontaneous activity, leading to a selective attenuation of the noxious thermal response. In contrast, the NK1 receptor selective agonist, [Met-OMe11]SP did not elicit such responses. In situ hybridisation histochemistry (ISHH) detection of PPD mRNA was employed as a tool to monitor the effects of tachykinin receptor antagonists on the delayed central genomic changes associated with carrageenan-induced inflammation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available