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dc.contributor.authorYoung, Marie R.en
dc.date.accessioned2018-05-22T12:50:44Z
dc.date.available2018-05-22T12:50:44Z
dc.date.issued1995en
dc.identifier.urihttp://hdl.handle.net/1842/30962
dc.description.abstracten
dc.description.abstractGlutamate, substance P (SP) and neurokinin A (NKA) are all found in fine primary afferent fibres and can be released upon noxious stimulation of the corresponding cutaneous receptive field. The possibility of a role in nociception for the metabotropic class of glutamate receptors (mGluRs) as well as those at which SP and NKA preferentially act (NKj and NK2), was investigated in the present study. Since protein kinase C (PKC) has been shown to be important in the mediation of noxious, but not non-nociceptive inputs, the potential role of this and several other signal transduction pathways in sensory inputs was assessed here, especially in the context of actions via mGluRs.en
dc.description.abstract(a) Extracellular recordings were made from single dorsal horn neurons (laminae III-V) in the spinal cords of chloralose/urethane anaesthetised rats. Activity evoked by innocuous brushing of the cutaneous receptive field was not reduced by ionophoresis of mGluR antagonists L-l-amino-3-phosphopropionic acid (AP3), (R,S)- or (S)-4-carboxy-3-hydroxyphenylglycine (CHPG). However, sustained elevated firing evoked by the application of the C-fibre selective chemical irritant mustard oil was significantly attenuated by L (but not D)-AP3 and (R,S)-CHPG. Approximately one fifth of dorsal horn neurons could be excited by ionophoresis of the mGluR agonist (lS,3R)-l-aminocyclopentane-l-3-dicarboxylic acid (ACPD), and this evoked activity was similarly reduced by L (but not D)-AP3 and (R,S)-CHPG.en
dc.description.abstract(b) Inhibitors of calmodulin/Ca++-dependent kinase (CamKII), phospholipase A2 (PLA2), protein kinase A (PKA) and non-receptor tyrosine kinases were ionophoresed during brush- and mustard oil-evoked activity. CamKII and PLA2 inhibitors were less effective in reducing innocuous rather than noxious inputs. Inhibitors of PKA and tyrosine kinases were equally effective in reducing all evoked activity. All of these antagonists, as well as two PKC inhibitors significantly decreased activity elicited by the ionophoresis of (1S,3R)-ACPD.en
dc.description.abstract(c) The behaviour of conscious rats in response to noxious mechanical and thermal stimulation of one hindpaw (non-inflamed or inflamed by an intraplantar injection of carrageenan) was monitored following an intrathecal injection of mGluR antagonists L-AP3 and (S)-CHPG, as well as GR82334 and L659,874, antagonists at NK] and NK2 receptors respectively. (S)-CHPG significantly increased withdrawal responses in each model to both mechanical and thermal stimulation, whereas L-AP3 was only effective in the inflamed paw. L659,874 was antinociceptive in thermal, but not mechanical, tests in the non-inflamed and inflamed paws. GR82334 did not alter latencies in any tests. However, a co-injection of GR82334 or L659,874 with each mGluR antagonist resulted in an apparent reversal of the analgesic effects observed when the mGluR antagonists were administered alone.en
dc.description.abstractThis investigation demonstrates a role for spinal cord mGluRs in the transmission of sustained nociception, possibly mediated by PKC, CamKII and PLA2. NK2 receptors appear to have a selective role in thermal inputs to the spinal cord, whereas this study provided no evidence for an overt role of NK] receptors in the nociceptive models assessed. It is possible that NK] receptors play a greater role in more prolonged or severe nociceptive inputs. The present data suggest however that not only NK2, but also NK] receptors exhibit a functional interaction with the influence of mGluRs on nociceptive thresholds.en
dc.publisherThe University of Edinburghen
dc.relation.isreferencedbyAlready catalogueden
dc.subjectAnnexe Thesis Digitisation Project 2018 Block 19en
dc.titleThe role of metabotropic glutamate and neurokinin receptors in mediating sustained nociceptive inputs to the spinal cord of the raten
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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