Curr Opin Invest Dr
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Curr Opin Invest Dr · Jan 2008
ReviewMultimodal analgesia: its role in preventing postoperative pain.
Postoperative pain is a complex and multifactorial symptom that requires a thoughtful approach using a variety of treatment modalities to obtain an optimal outcome after surgery. Multimodal (or 'balanced') analgesia represents an approach to preventing postoperative pain where the patient is administered a combination of opioid and non-opioid analgesic drugs that act at different sites within the central and peripheral nervous systems in an effort to minimize opioid use and, therefore, to decrease opioid-related side effects. Despite widespread interest in this concept from both the anesthesia and surgery communities, very few prospective, randomized, controlled clinical investigations have been conducted that utilize this approach to improving patient comfort and facilitating recovery after surgery. ⋯ More recently, clinical investigators have begun to examine the beneficial effects of combined multimodal approaches in preventing postoperative pain by utilizing combinations of non-opioid analgesics to minimize the opioid analgesic requirements and opioid-related side effects. This review explores the theoretical basis for multimodal analgesia and the existing scientific evidence supporting its benefit in improving pain control after surgery. Recent investigations that have examined the impact of this therapeutic approach for improving clinically meaningful patient outcomes after surgery will be discussed.
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Curr Opin Invest Dr · Jan 2008
ReviewThe role of tetrodotoxin-resistant sodium channels in pain states: are they the next target for analgesic drugs?
Neuropathic pain, a persistent chronic pain resulting from damage to the central or peripheral nervous system, is a condition that severely affects the quality-of-life of millions of individuals worldwide. The treatment of neuropathic pain is still an unmet medical need; however, recent advances in our understanding of mechanisms underlying the perception and transmission of painful stimuli offer significant potential for improvement of therapies directed to neuropathic pain. Ectopic activity in damaged and dysfunctional sensory afferents is believed to have a role in the generation and maintenance of neuropathic pain. ⋯ In fact, NaV blockers have been clinically validated as treatments for neuropathic pain. However, current drugs are weak, non-selective inhibitors of NaVs with dose-limiting CNS and cardiovascular side effects that prevent their use in long-term therapy. Selective NaV tetrodotoxin-resistant channels (NaV 1.8 and NaV 1.9) are expressed exclusively in nociceptive neurons in the DRGs where they play a key role in normal and/or pathological pain sensation, providing an opportunity for the development of novel peripheral analgesics with a better safety profile.
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Curr Opin Invest Dr · Jan 2008
ReviewCannabinoids for the treatment of neuropathic pain: clinical evidence.
Neuropathic pain is a worldwide epidemic that occurs in 3 to 8% of individuals in industrialized countries and is often refractory to existing treatments. Drugs currently available to target neuropathic pain are, at best, moderately effective and include antidepressants, gabapentin, NMDA receptor antagonists, as well as other anticonvulsants, all of which are limited by their adverse-effect profiles. Cannabinoid drugs are emerging as a promising class of drugs to treat neuropathic pain and have been tested for analgesic effects in a range of chronic pain conditions. ⋯ Data from large, well-controlled studies show that cannabinoids are moderately effective in reducing chronic pain and that side effects are comparable to existing treatments, suggesting that cannabinoids can play a useful role in the management of chronic pain. Like other drugs for neuropathic pain, cannabinoids have a dose titration that is limited by psychoactive side effects. The development of cannabinoid drugs to target neuropathic pain with improved therapeutic ratios will depend upon the development of cannabinoid treatments with reduced psychoactivity.
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Curr Opin Invest Dr · Jan 2008
ReviewMethylnaltrexone, a new peripheral mu-receptor antagonist for the prevention and treatment of opioid-induced extracerebral side effects.
Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a methyl group. The intravenous formulation of methylnaltrexone is currently in phase III clinical trials for the potential treatment of postoperative ileus.