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Contribution of metabotropic glutamate receptors to spinal nociceptive transmission in the rat spinal cord

Boxall, Sarah Jane; (1997) Contribution of metabotropic glutamate receptors to spinal nociceptive transmission in the rat spinal cord. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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n this thesis I have examined the contribution of metabotropic glutamate receptors (mGluRs) to spinal nociception in control conditions and following inflammatory hyperalgesia in the rat. In situ hybridisation studies showed mGluR mRNA expression in all areas of the adult spinal cord with distribution being specific for each subtype. There was a general decrease in subtype expression during development, with the most marked changes in mGluR3 and mGluR5 mRNAs. Following the induction of inflammatory hyperalgesia in juvenile (postnatal day 11-13) rats, no changes were seen in the levels of expression of mGluR1, 2, 4, 5 and 7 mRNAs. However, a significant bilateral increase in mGluR3 mRNA expression in the superficial dorsal laminae was seen 1 day after the onset of inflammation. This change in expression mirrored the time course for mechanical hyperalgesia and allodynia in behavioural studies. In an in vitro preparation of the hemisected spinal cord, the specific mGluR agonist, (1S,3R)-ACPD, produced a concentration-dependent, reversible ventral root depolarisation, which was enhanced in UV-treated animals. The specific, non-selective mGluR antagonist MCPG attenuated (1S,3R)-ACPD responses in naive and UV-treated animals. In naive preparations, the NMDA receptor antagonist, D-AP5, was ineffective against (1S,3R)-ACPD responses while in UV-treated animals it decreased the maximum response. MCCG (group II antagonist) enhanced (1S,3R)-ACPD responses in naive animals and attenuated the same response in UV-treated animals. The more group II selective agonists, (1S,3S)-ACPD and L-CCG-I evoked responses in both naive and hyperalgesic animals. MCCG attenuated responses to (1S,3S)-ACPD in both preparations. These data suggest an mGluR component in the spinal cord and provide evidence for a tonic NMDA component during hyperalgesia. Spinal reflex activity was also studied in the hemisected spinal cord. Both single shock and train-evoked responses revealed an mGluR component, although in established hyperalgesia, no further mGluR component was detected. These findings suggest that mGluRs may contribute to the development of enhanced spinal activity, however their importance could be shadowed by NMDA receptor activity in established hyperalgesic states.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Contribution of metabotropic glutamate receptors to spinal nociceptive transmission in the rat spinal cord
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Metabotropic glutamate receptors; Spinal cord; Spinal nociceptive transmission
URI: https://discovery.ucl.ac.uk/id/eprint/10104985
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