The balance between safety and efficacy is important in pharmacotherapy. When the indication of a registered drug shifts to another disease or a different patient population, studies on safety and... Show moreThe balance between safety and efficacy is important in pharmacotherapy. When the indication of a registered drug shifts to another disease or a different patient population, studies on safety and efficacy need to be performed. Ketamine is a relatively __old__ drug and used for almost 50 years as an anesthetic. Recently there has been a renewed interest for the treatment of therapy-resistant chronic pain with subanesthetic doses of ketamine. This thesis describes the effects of S-ketamine in patients with chronic pain (CRPS-1 and fibromyalgia patients) and healthy volunteers. In chronic pain patients (e.g. CRPS-1) pain relief can last for months after long-term intravenous ketamine infusions, but short-term S-ketamine had no long-term efficacy in fibromyalgia patients. S-ketamine can cause a wide range of side-effects which limits its use. Therefore studies were performed in healthy volunteers to expand the knowledge on S-ketamine and the main metabolite S-norketamine to further characterize side-effects (specifically neurocognitive effects). S-norketamine does not contribute to S-ketamine__s analgesic effects and can therefore not serve as an alternative. Show less
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
