Articles: hyperalgesia.
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Best Pract Res Clin Anaesthesiol · Mar 2007
ReviewThe impact of opioid-induced hyperalgesia for postoperative pain.
Clinical evidence suggests that--besides their well known analgesic activity - opioids can increase rather than decrease sensitivity to noxious stimuli. Based on the observation that opioids can activate pain inhibitory and pain facilitatory systems, this pain hypersensitivity has been attributed to a relative predominance of pronociceptive mechanisms. 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, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. ⋯ Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days in rodents, and also in humans large-doses of intraoperative micro-receptor agonists were found to increase postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients is often associated with a requirement for increasing doses and the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha2-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor/selectivity.
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Noxious C-fibre stimulation produces increased sensitivity within the injured area (primary hyperalgesia), and a surrounding zone of secondary hyperalgesia. As significant changes in nociceptive processing occur during development, we compared C-fibre induced primary and secondary hyperalgesia in rat pups aged 3, 10 and 21 postnatal (P) days. Hyperalgesia was measured by electromyography flexion reflex recordings following mustard oil or capsaicin at the site of (primary hyperalgesia), or distant to (secondary hyperalgesia) hindpaw mechanical stimuli. ⋯ These results provide evidence that primary and secondary hyperalgesia are differentially modulated during development. Furthermore, since ERK activation is required for secondary hyperalgesia, phosphoERK expression can be used to map the spatial distribution of neuronal activation in the spinal cord. Understanding changing responses to injury in the developing nervous system is important for clinical paediatric practice, and will enhance our ability to target the most effective site with a developmentally appropriate analgesic regime.
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Recently, it has been appreciated that in addition to their antinociceptive properties, opioid analgesics also can enhance pain sensitivity (opioid-induced hyperalgesia [OIH]). OIH may enhance preexisting pain and contribute to dose escalation, tolerance, and misuse/abuse of opioids. Better information is needed to determine which opioid or opioid combinations may be least likely to produce OIH and therefore possibly represent better choices for pain management. Herein the authors have examined the hyperalgesic and antinociceptive properties of racemic methadone and its enantiomers alone and in combination with morphine in rats. Methadone is of particular interest because it possesses both micro-receptor agonist and N-methyl-d-aspartate receptor antagonist activities. ⋯ The current findings with methadone are supportive of previous findings implicating mu-opioid and N-methyl-d-aspartate receptor mechanisms in OIH. Better understanding of OIH may help in choosing the most appropriate opioids for use in the treatment of pain.
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A patient was treated for several years with high doses of opioids for malignant pain. During a recent hospitalization, the patient's pain remained uncontrolled despite escalating doses of various opioids. ⋯ Methadone, because of its NMDA antagonist properties, offers an effective treatment for OIH. The use of methadone for analgesia is complex and should be undertaken only by practitioners who have appropriate experience.
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Opioids have been successfully used for the management of acute and cancer-related pain. Concerns regarding side effects, tolerance, dependence, addiction, and hyperalgesia have limited the use of opioids for the management of chronic nonmalignant pain. This article will review updated information from both clinical and preclinical studies regarding opioid-induced hyperalgesia, tolerance, and dependence. The implications of these issues in clinical opioid therapy also will be discussed.