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Title: Factors influencing gene expression in the rat spinal cord following noxious stimulation
Author: Gardner, E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
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Noxious stimulation increases the levels of AP-1 and other immediate early gene (IEG) proteins in the spinal cord. These transcription enhancers regulate the expression of a second set of genes which have the potential to cause long-term changes in neuronal phenotype and function. In the spinal cord, such changes are manifested as hypersensitivity to stimulation leading to chronic pain states. One putative target of IEG control is the gene encoding the opioid peptide dynorphin. Robust increases in this gene are seen in the spinal cord in animal models of pain and its presence has been correlated with alteration of neuronal function. This study has used the rat formalin test as a model for gene activation in the spinal cord. The stimulus-specificity of changes in gene expression caused by hind-paw injection of dilute formalin was compared with similar injection of the neurotoxin capsaicin. The contribution of different neurotransmitters to the IEG response was assessed by pharmacological means in formalin-injected animals. Finally, the presence of functional IEG proteins in the spinal cord of formalin-injected animals was assessed by gel shift assay. Formalin and capsaicin produced different physiological and behavioural responses; formalin provoked long-lasting inflammation and prolonged biphasic nociceptive behaviour, whilst capsaicin was non-inflammatory and without a profound effect on behaviour. However, both treatments caused similar short-term upregulation in IEG expression in the spinal cord followed by an increase in preprodynorphin mRNA. Thus even brief noxious stimulation, as caused by capsaicin, was capable of significantly altering neuronal gene expression. Pharmacological investigation of the formalin test showed that both phases of the behavioural response could be selectively inhibited by non-NMDA and NMDA glutamate antagonists (NBQX and HA966).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available