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 (NK<SUB>1</SUB> and NK<SUB>2</SUB>), 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 PLA<SUB>2</SUB>. NK<SUB>2</SUB> 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<SUB>1</SUB> receptors in the nociceptive models assessed. It is possible that NK<SUB>1</SUB> receptors play a greater role in more prolonged or severe nociceptive inputs. The present data suggest however that not only NK<SUB>2</SUB>, but also NK<SUB>1</SUB> receptors exhibit a functional interaction with the influence of mGluRs on nociceptive thresholds.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:664166 |
| Date | January 1995 |
| Creators | Young, Marie R. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/30962 |
Page generated in 0.0015 seconds