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Brainstem control of spinal sensory processing in the rat

Bee, Lucy Ann; (2008) Brainstem control of spinal sensory processing in the rat. Doctoral thesis , UCL (University College London). Green open access

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Brainstem structures engage descending facilitatory and inhibitory neurones to potentiate or suppress the onward passage of sensory inputs from spinal loci to the brain. The final output for this bidirectional control is the rostral ventromedial medulla (RVM), which shapes sensory processing via relays between the spinal cord and brain, ultimately influencing pain perception via On and Off cells. I aimed to determine the predominant nature of this supraspinal control in the normal anaesthetised state and to see how descending influences may change with pathophysiology. By injecting a local anaesthetic into the RVM of normal rats and measuring the evoked responses of dorsal horn neurones to various stimuli, I demonstrated a dominant facilitation of spinal neuronal responses to high-threshold stimuli. Following nerve injury, reductions in spinal cord activity induced by intra-RVM lignocaine further encompassed responses to low-threshold stimuli, and the proportion of neurones influenced in this manner increased. The increase in descending facilitatory influences in the neuropathic state is suggestive of nerve injury induced plasticity. I additionally employed targeted ablation techniques using the neurotoxin saporin to show that mu-opioid receptor expressing cells in the RVM underlie spinal facilitation. This pathway involves spinal 5HT3 receptors, since typical responses to spinal ondansetron, a 5HT3 receptor antagonist, require the integrity of RVM MOR cells. Importantly, I showed that these neurones are critical for maintaining behavioural hypersensitivities following nerve injury, and are necessary for the full inhibitory efficacy of spinal pregabalin in the neuropathic state. These results define a pathway that could be pivotal for linking the sensory and affective components of pain. Understanding this connection, and how one component influences the other, may help explain the variable valence of suffering that is experienced by patients in response to the same nervous system injuries, and explain differences in treatment outcomes in an otherwise consistent population.

Type: Thesis (Doctoral)
Title: Brainstem control of spinal sensory processing in the rat
Identifier: PQ ETD:591409
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1444107
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