The clinical characteristics of Complex Regional Pain Syndrome (CRPS) are defined by pain and various combinations of sensory disturbances, autonomic features, and sudomotor and trophic changes.... Show moreThe clinical characteristics of Complex Regional Pain Syndrome (CRPS) are defined by pain and various combinations of sensory disturbances, autonomic features, and sudomotor and trophic changes. Furthermore, patients with CRPS may suffer from movement disorders, of which dystonia is the most prevalent. Dystonia of CRPS can affect multiple extremities, is often resistant to treatment and seems to have a poor prognosis. Reliable information on the nature, chronology and clinical determinants of dystonia in CRPS patients is lacking but could provide better insight in the underlying pathophysiological mechanism. The results of our studies on clinical and neurophysiologic aspects of patients with multiple CRPS and MDs in CRPS provided data that suggest disturbances at multiple levels of the CNS. Maladaptive neural plasticity likely is an important mechanism underpinning the MDs that may occur in CRPS. The presence of disturbances at multiple levels of the central nervous system parallels recent hypotheses on the underlying mechanisms suggested for other types of dystonia. Finally, the study on intrathecal baclofen administration in patients with CRPS and dystonia showed marked improvement of dystonia and pain scores after one year. Show less
The research in this thesis is aimed at the elucidation of the role of the glucocorticoid receptor (GR) in hippocampal neuroplasticity and functioning. To achieve this, we have developed a novel... Show moreThe research in this thesis is aimed at the elucidation of the role of the glucocorticoid receptor (GR) in hippocampal neuroplasticity and functioning. To achieve this, we have developed a novel method to specifically knockdown GR in a discrete cell population of the mouse brain. In this thesis I report silencing of GR expression selectively in a population of neuronal progenitors and immature neurons of the dentate gyrus, using RNA-interference (RNAi) delivered by a lentiviral vector. Characterization of these cells resulted in the discovery that GR knockdown causes a striking modulation of hippocampal neurogenesis and remodelling of hippocampal circuitry. Functional studies further revealed consequences of GR knockdown for contextual memory performance and behavioural coping strategies during stressful conditions. The results demonstrate the feasibility to apply RNAi in discrete cell populations for study of the action mechanism of glucocorticoids underlying control of neuroplasticity and behaviour. Show less
