Seagrove, Lucinda Claire; (2004) Characteristics, plasticity and pharmacology of lamina I neurones in the rat spinal cord: An electrophysiological study. Doctoral thesis (Ph.D.), University College London.

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Abstract

The response characteristics to peripheral stimulation and the pharmacological properties of lamina I superficial dorsal horn neurones, have been assessed and analysed in this study. Lamina I neuronal responses to electrical, mechanical and thermal stimuli applied to the peripheral receptive field area were quantified. From this it was found that the majority of lamina I neurones (50-71%) were nociceptive specific (NS) in response characteristics in all animal models tested. Further characterisations of lamina I neuronal responses were made in neuropathic animals and after ablation of lamina I/III NK1 receptor expressing neurones, where only small increases in neuronal responses were seen. The role of ionotropic glutamate receptors in lamina I neuronal responses to peripheral electrical stimuli were evaluated using spinally administered selective receptor antagonists for AMPA (NBQX), AMPA/ kainite (CNQX), kainate (LY293558), NMDA (APV) and NR2B (Ifenprodil and ACEA-1244) receptors. AMPA and kainate receptors play a major role in lamina I neuronal responses (NBQX, 50?g/ 50?l, 53-98% reduction, A?-fibre, C-fibre, Post-Discharge and XS-Spike responses), yet the NMDA receptors have comparatively smaller roles as compared with deeper dorsal horn neurones which have been previously characterised (APV, 500?g/ 50?l, 19% reduction in lamina I neurones). The majority of these excitatory amino acid receptor antagonists were also assessed in lamina I neurones recorded from neuropathic rat models, to evaluate any potential changes arising from peripheral nerve damage of which only minor differences were evident. The role of the ionotropic GABAA receptor was investigated using a spinally administered GABAA receptor antagonist (Bicuculline) on lamina I neuronal responses. GABAA receptors appear to exert inhibitory influences on both electrical and mechanical response characteristics (50?g/ 50|?l, 279 69% of A?-fibre response and 308 115, 277 96 von Frey 9, 30g mechanical responses respectively). Following nerve injury, their role was less pronounced in the mechanically evoked response, yet the facilitation evoked by Bicuculline of the A-? fibre response was similar. The role of the glycine receptor in lamina 1 neuronal responses in normal models was also similarly investigated using a spinally administered glycine receptor antagonist (Strychnine). However glycine receptors appeared to play a smaller although noticeable role in lamina I neuronal response properties. Finally the role of the 5HT3 receptor (using the 5HT3 receptor antagonist Ondansetron) in lamina I neuronal responses to electrical and naturally evoked stimuli was assessed in a model whereby neurones containing the NK1 receptor were selectively ablated as well as a control model. Reductions in the electrically evoked responses were seen in both models, however larger reductions were more common in the control group (10-100?g/ 50?l Ondansetron, 26-82% reduction of all electrically evoked responses). The results provide a detailed account of the response properties of lamina I neurones in the rat and suggest that their high threshold properties may result from a combination of a lack of a major NMDA component to their responses and an active GABAA receptor inhibition.

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