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dc.contributor.advisorRoche, Michelle
dc.contributor.advisorFinn, David
dc.contributor.authorBurke, Nikita
dc.date.accessioned2014-04-07T13:22:03Z
dc.date.available2015-01-23T15:51:25Z
dc.date.issued2013-12-18
dc.identifier.urihttp://hdl.handle.net/10379/4266
dc.description.abstractDepression and chronic pain share an intricate, complex relationship, the comorbidity of which is reported to affect up to 80% of patients. This thesis demonstrated enhanced nociceptive responding to mechanical and cold, but not heat, stimuli in a well-validated animal model of depression, the olfactory bulbectomised (OB) rat. In addition, early life stress in the form of maternal deprivation (MD) resulted in enhanced nociceptive responding to mechanical and heat, but not cold, stimuli. OB animals exhibited exacerbated cold, but not mechanical, allodynia following spinal nerve ligation (SNL), a clinically relevant model of neuropathic pain. In addition, MD female, but not male, rats exhibited exacerbated mechanical and cold allodynia following SNL. Thus, neuropathic pain-related behaviour is enhanced in two models of affective disorders in a stimulus- and sex-dependent manner. Despite the high comorbidity of these disorders, the neurobiological mechanisms mediating the relationship between affective disorders and chronic pain remain unknown. Evidence suggests that monoamines and neuroimmune mediators play a role in the relationship between depression and pain. This thesis demonstrated that the enhanced SNL-induced cold allodynia observed in OB rats was accompanied by reduced serotonergic neurotransmission in the hippocampus, reduced inflammatory cytokine gene expression in the amygdala and increased cytokine gene expression and glial activation in the prefrontal cortex (PFC). In addition, early life stress and SNL differentially altered immune gene expression in the PFC and hippocampus in a sex-dependent manner. Pharmacological studies were subsequently employed in order to further probe the role of monoamines and neuroimmune mediators in the OB-related changes in nociceptive responding, prior to and following SNL. Chronic treatment with amitriptyline (a tricyclic antidepressant and first-line treatment for neuropathic pain) and minocycline (an inhibitor of microglial activation) elicited an antidepressant-like effect, but did not alter basal nociceptive responding in the OB rat. However, chronic amitriptyline and minocycline treatment differentially altered neuropathic pain-related behaviour in the presence or absence of a depressive-like phenotype. In brief, amitriptyline attenuated SNL-induced cold allodynia and thermal hyperalgesia, but not mechanical allodynia, in sham (control) rats. In contrast, amitriptyline attenuated SNL-induced mechanical allodynia, but not cold allodynia or thermal hyperalgesia in OB rats. Chronic minocycline treatment attenuated SNL-induced cold and mechanical allodynia in both sham and OB rats. Thus, enhancing monoamines and blocking microglial activation elicits antidepressant-like effects and attenuates SNL-induced mechanical allodynia in the OB model of depression. These studies improve our understanding of supraspinal mechanisms underlying pain, affect and the interaction between these processes, indicating that monoamines and neuroimmune mediators may, in part, underlie this association.en_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectDepressionen_US
dc.subjectPainen_US
dc.subjectMicrogliaen_US
dc.subjectCytokinesen_US
dc.subjectSpinal nerve ligationen_US
dc.subjectOlfactory bulbectomyen_US
dc.subjectEarly life stressen_US
dc.subjectMonoaminesen_US
dc.subjectAmitriptylineen_US
dc.subjectMinocyclineen_US
dc.subjectBrainen_US
dc.subjectMedicine, Nursing and Health Sciencesen_US
dc.titleAltered nociceptive responding in animal models of affective disorders: role of monoamines and immune mediatorsen_US
dc.typeThesisen_US
dc.contributor.funderCollege of Medicine, Nursing and Health Sciences, NUI Galwayen_US
dc.local.noteDepression and chronic pain frequently co-occur, however the neurobiological substrates underlying this relationship remain unknown. This thesis demonstrated that basal and neuropathic pain responding is enhanced in two animal models of depression, the olfactory bulbectomised and maternal deprivation models. These behaviours were accompanied by alterations in the monoaminergic and immune systems in the brain. These studies improve our understanding of supraspinal mechanisms underlying pain, affect and the interaction between these processes, indicating that monoamines and neuroimmune mediators may, in part, underlie this association.en_US
dc.local.finalYesen_US
nui.item.downloads1890


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Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland