The effect of nerve injury on behavioural selection and its relationship to prefrontal cortex function

The disruption of complex behaviours is often observed in chronic neuropathic pain patients, and involves emotional disturbances, reduced motivation and impairments in cognitive function. The appropriate coordination and selection of these behaviours often relies on the proper function of the brain region known as the prefrontal cortex. The overall aim of the work presented in this thesis was to investigate whether alterations in complex behaviours in the neuropathic pain state, are associated with altered regulation of prefrontal cortex function. A series of experiments were performed to investigate the effect of neuropathic injury on the expression of emotional, motivational and cognitive aspects of behaviour, using an animal model of neuropathic pain known as the chronic constriction injury (CCI). It was observed from different behavioural experiments that following CCI, a sub-population of rats exhibited impairments in emotional behaviours. In addition, experiment to assess cognitive function did not show any apparent effect of neuropathic injury on cognition, but when neuropathic rats are acutely stressed, their motivational behaviours were impaired. Following on from this molecular, neurochemical and anatomical experiments on the prefrontal cortex revealed a distinct effect of anaesthesia, surgery and nerve injury on the neurotrophic signaling profile in the prefrontal cortex; specific effects of neuropathic injury and acute stress on dopamine concentrations, and significant effects of acute stress on serotonin levels in the prefrontal cortex. Anatomical studies looking at the relationship between the amygdala and the prefrontal cortex revealed neuropathic injury increased ongoing activation of amygdala cells, but not prefrontal cortex projecting amygdala cells. Work presented in this thesis provides evidence for a working animal model that can reveal the impact neuropathic injury has on altering complex behavioural responses and neural processes