Der Schmerz
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Opioids are frequently used for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both, pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system and descending facilitation have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. ⋯ Brief exposures to mu-receptor agonists induce long-lasting hyperalgesic effects for days. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs such as NMDA antagonists, alpha(2)-agonists, or nonsteroidal anti-inflammatory drugs (NSAID), opioid rotation, or combinations of opioids with different receptor selectivity.
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Opioids are valuable analgesics, capable of providing pain relief and functional improvement not only in patients with cancer-related pain, but also in chronic noncancer-related pain patients. However, recent data have shown that the increasing prescription of opioids is associated with a rise in aberrant drug-related behaviour. The causes of this behaviour are multifactorial. ⋯ Assessment of the progress of therapy is based on the following factors: analgesic efficacy, adverse side effects, functional status and aberrant drug-related behaviour. In the absence of a successful opioid therapy, the treatment must be discontinued to avoid iatrogenic damage, substance abuse and illegal diversion. After discontinuation of the therapy, a comprehensive interdisciplinary re-evaluation is required.
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A total of 121 patients with at least a 3-year history of opioid use were evaluated by a standardized interview during a clinical visit or telephone call. Assessed items were the present and former drug medication, daily doses, withdrawals, contentment with the treatment, positive/negative treatment effects, average/maximum pain and others. ⋯ chi(2), ANCOVA and survival analysis. Of 121 patients (frequency of withdrawal 14.8% mainly due to lack of efficacy) with an average treatment time of 66 months (37-105 months; 80,264 days; 87% more than 5 years), 103 (85%) still took an opioid step II or III according to the WHO analgesic ladder. Patients further treated in the pain clinic stopped significantly less frequently than patients treated by GPs or other non-specialised physicians (5 versus 23%). Patients with long-term opioid intake revealed significantly lower pain intensity and higher contentment with the pain management and achieved improvement (global, quality of life and physical state). Changes of opioid dosages during the 5 years were inconsistent (no change 33%, decrease 16%, slight increase 27%, high increase 19%). However, the number of patients with high dose increased from 6 to 23 due to significant loss of efficacy (proved in the morphine subgroup, p<0.05). The survey demonstrates a very low frequency of withdrawal in patients with long-term opioid medication after initial response without evidence for tolerance development, especially if their treatment is controlled in a pain centre.
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Recent advances in knowledge about gene structure derived from the human genome project has also revealed data on genomic variation and their possible impact on complex and acute diseases as well as pharmacotherapy. The hypothesis of a genetic predisposition for complex diseases such as pain syndromes, side effects, and adverse outcomes challenging the clinician is ready to be tested by advanced genetic-epidemiologic study designs employing the latest genotyping technology. ⋯ Genetic differences in drug kinetics and dynamics, e.g., differences in metabolism or genetic variations of the drug target (e.g., receptors) will be of importance in the future. Pharmacogenetics can individualize pharmacotherapy and improve care by predicting the optimal dose and avoiding side effects and toxicity in individual patients.