Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety

University of Oxford, Oxford, England, United Kingdom
Pain (Impact Factor: 5.21). 01/2005; 112(3):372-80. DOI: 10.1016/j.pain.2004.09.019
Source: PubMed

ABSTRACT Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.

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    • "The central blockade of opioid receptors provides the analgesic property of opioids, but the peripheral blockade that doesn't contribute much to analgesia leads to a variety of side effects instead [3] [5] [6]. With the dramatic increase in opioid use in recent years, the incidence of opioidinduced side effects has also seen a momentous increase [7] [8]. "
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    ABSTRACT: Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with advanced illness. Some studies have reported that OIC is so intolerable in some patients that they skip their opioid medications and bear pain instead of OIC. Laxatives have commonly been used as a prophylaxis and treatment of OIC but they are frequently ineffective because the commonly available laxatives do not target the underlying mechanism of OIC, which is the blockade of peripheral mu-receptors. Recently, there have been a number of advances in the treatment of OIC, which any physician involved with opioid-prescribing discipline should be aware of. This review will update the new options and strategies available for treating OIC along with the relevant clinical trials. Finally, this review also provides a recommendation on the preferred way to approach a patient with OIC in the modern era as well as highlight on the importance of doctor-patient communication in this setting.
    Scandinavian Journal of Gastroenterology 06/2015; 50(11):1-8. DOI:10.3109/00365521.2015.1054423 · 2.36 Impact Factor
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    • "Concerning adverse events with opioid use, Kalso, et al.10 reported adverse events from use of opioids in treating chronic non-cancer pain, including OA. They analyzed available randomized, placebo-controlled trials using the Oxford Pain Relief Database, as well as Medline, EMBASE, and the Cochrane Library.10 Specific adverse events were reported in most studies. "
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    ABSTRACT: Purpose Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. Materials and Methods Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. Results Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. Conclusion Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
    Yonsei Medical Journal 09/2014; 55(5):1379-85. DOI:10.3349/ymj.2014.55.5.1379 · 1.29 Impact Factor
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    • "This distribution parallels differences in species sensitivity to peripheral administration of opioids suggesting that when expressed, DRG Kir3 subunits actively participate in opioid analgesia. Indeed, intraplantar injection of MOR agonists does not produce analgesia in mice (Nockemann et al., 2013) but effectively mitigates pain in inflammatory or neuropathic rat models (Stein et al., 1989; Obara et al., 2009; Chung et al., 2013; Nockemann et al., 2013) as well as postoperative and arthritic pain in humans (Kalso et al., 2004; Vadivelu et al., 2011). Moreover, the active contribution of Kir3.2 channels to peripheral opioid analgesia has now been experimentally established using transgenic mice genetically engineered to express these subunits in sensory neurons. "
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    ABSTRACT: Opioids are among the most effective drugs to treat severe pain. They produce their analgesic actions by specifically activating opioid receptors located along the pain perception pathway where they inhibit the flow of nociceptive information. This inhibition is partly accomplished by activation of hyperpolarizing G protein-coupled inwardly-rectifying potassium (GIRK or Kir3) channels. Kir3 channels control cellular excitability in the central nervous system and in the heart and, because of their ubiquitous distribution, they mediate the effects of a large range of hormones and neurotransmitters which, upon activation of corresponding G protein-coupled receptors (GPCRs) lead to channel opening. Here we analyze GPCR signaling via these effectors in reference to precoupling and collision models. Existing knowledge on signaling bias is discussed in relation to these models as a means of developing strategies to produce novel opioid analgesics with an improved side effects profile.
    Frontiers in Cellular Neuroscience 07/2014; 8:186. DOI:10.3389/fncel.2014.00186 · 4.29 Impact Factor
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