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Title: The role of metabotropic glutamate and neurokinin receptors in mediating sustained nociceptive inputs to the spinal cord of the rat
Author: Young, Marie R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Glutamate, 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 (NK1 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. (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-1-amino-3-phosphopropionic acid (AP3), (R,S)- or (S)-4-carboxy-3-hydroxyphenylglycine (CHPG). This 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 NK1 receptors in the nociceptive models assessed. It is possible that NK1 receptors play a greater role in more prolonged or severe nociceptive inputs. The present data suggest however that not only NK2, but also NK1 receptors exhibit a functional interaction with the influence of mGluRs on nociceptive thresholds.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available