Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pfretschner, A.
The role of noradrenaline in the treatment of painful diabetic neuropathy (PDN)
[ Diplomarbeit ] Medical University of Graz; 2014. pp. 57
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Sandner-Kiesling Andreas
- Szilagyi Istvan - Szilard
- Altmetrics:
- Abstract:
- Treatment of patients suffering from chronic neuropathic pain is known to be difficult and partial frustrating for patient and therapist. In particular therapy of the subgroup suffering from painful diabetic neuropathy (PDN) tends to be unsatisfying. Beside the limitations, as a result of insufficient analgesic efficacy of non steroidal anti-inflammatory drugs (NSAIDs) and opioid-analgesics, also the established use of antidepressants is limited by their side effects and co-morbidities the patients bring with. Since the 1960s antidepressants are applied in treatment of chronic neuropathic pain. International guidelines rank tricyclic antidepressants (TCAs), especially the substance amitryptiline, as first line treatment. During the last years duloxetine, an selective serotonin and noradrenaline reuptake inhibitor (SNRI) with less side effects, was established as alternative to TCAs. The analgesic mechanism of different antidepressant substance-classes is still unknown in detail. Recent clinical studies, which explored the analgesic effect of antidepressants, found evidence for enhanced levels of noradrenaline in the synaptic cleft, to play the key-role. These suggestions are supported by the results of studies, testing the analgesic effect of selective serotonin reuptake-inhibitors (SSRI). There was hardly any or no effect. Some trials, exploring the mechanism of action of the opioid substances tapentadol and tramadol, had similar results. These two substances show, besides their effect at the opioid ¿-receptor, also action as serotonin-reuptake inhibitors. In contrast to the analgesic effect through enhanced levels of noradrenaline, enhanced levels of serotonin just cause side effects, such as fatigue, dizziness, loss of libido, gastro-intestinal complaints etc. Reboxetine is the only selective noradrenaline-reuptake-inhibitor, yet only applied as antidepressant for the treatment of mild to moderate depression. Some trials testing its analgesic effect on healthy probands and animal experiment found auspicious results. The analgesic efficacy was similar to amitryptiline and duloxetine but showed less side effects. In addition to standardised screening tools for neuropathic pain, quantitative sensory testing (QST) is yet the most objective clinical tool to subgroup different types of neuropathic pain and to observe clinical changes. According to this findings and the background, suggesting enhanced levels of noradrenaline as the key-role in analgesia through antidepressants, we propose a pilot study testing reboxetine as a co-analgesic in PDN. Hence its established use in treatment of neuropathic pain and similar side effects, we suggest duloxetine as reference substance and QST to subgroup and to observe clinical changes in PDN.