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Title: Pharmacological studies of prostanoids and other substances on sensory nerves in arthritic rats
Author: Birrell, Graham James
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Intra-arterial (i.a.) injection of 5-hydroxytryptamine (5-HT), excited articular nociceptors from normal and arthritic joints. Responses consisted of two components: (a) a fast transient burst of activity mediated by a 5-HT3-receptor, followed by (b) a delayed, longer-lasting excitation mediated by a 5-HT2-receptor. These responses were shown to occur both in vivo and in vitro. 5-HT also increased the mechanical responsiveness of articular mechanonociceptors via a 5-HT3-receptor. Sensory receptors in arthritic joints were more sensitive to 5-HT to those from normal joints. Administration of the 5-HT3- or 5-HT2-receptor antagonists caused short-lasting reductions in background activity in arthritic joints, as well as in normal joints in which activity had increased following administration of 5-HT. In normal joints, i.a. injection of PGE2, PG12 or the selective IP-receptor agonist cicaprost, excited and caused mechanical sensitization of articular mechanonociceptors. Potentiation of the short-lived excitatory and sensitizing effects of i.a. injected bradykinin on these receptors was also shown. Examination of the effects of PGE2, PG12 and cicaprost in vivo or PGE2, cicaprost, PGD2, and PGF2 alpha in vitro, produced a rank order of potency of PG12 = cicaprost > > PGE2 > > PGD2 = PGF2 alpha In arthritic rats injection of cicaprost and, to a lesser extent, PGE2 was effective in increasing the mechanical responsiveness and resting discharge of articular mechanonociceptors previously depressed by i.v. lysine acetylsalicylate. These results provide evidence for the involvement of IP-receptors, and perhaps EP-receptors, in the excitatory and sensitizing actions of the prostanoids on articular nociceptors, and suggest that PGI2 is the major endogenous prostanoid responsible for the mechanonociceptor sensitization seen in arthritic rat ankle joints. Overall the results suggest that more than one mediator is required to produce conditions of mechanonociceptor sensitization seen in arthritic rat ankle joints. However, as modulators of the responsiveness of nociceptors to other mediators, and as potent excitants themselves, the prostanoids, and in particular PGI2, probably play a major role in the alterations in nociceptor sensitivity seen in arthritic joints.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available