The Clinical journal of pain
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To review the quality of adverse event reporting for published randomized controlled trials (RCTs) focusing on acupuncture for pain reduction. With the release of the Consolidated Standards of Reporting Trials (CONSORT) in 2001, the quality of published RCTs has improved. To improve reporting on adverse events, CONSORT expanded the section on harms (adverse events) in 2004. This paper evaluates whether the updated harms guidelines have been implemented in RCTs evaluating acupuncture for pain relief. ⋯ On the basis of our findings, acupuncture clinical trials for pain reduction have yet to comprehensively meet CONSORT's guidelines for adverse event reporting. Acupuncture is commonly used by patients experiencing pain and although typically viewed as a benign and minimally invasive therapy, serious adverse events have been reported in the literature. To effectively and comprehensively document and understand these events, routine reporting according to CONSORT's harms guidelines should become the norm. Both science and patients are served by accurately evaluating the safety of acupuncture for patient populations experiencing pain.
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Use of prescription opioids for chronic pain is increasing, as is abuse of these medications, though the nature of the link between these trends is unclear. These increases may be most marked in patients with mental health (MH) and substance use disorders (SUDs). We analyzed trends between 2000 and 2005 in opioid prescribing among individuals with noncancer pain conditions (NCPC), with and without MH and SUDs. ⋯ Chronic use of prescription opioids for NCPC is much higher and growing faster in patients with MH and SUDs than in those without these diagnoses. Clinicians should monitor the use of prescription opioids in these vulnerable groups to determine whether opioids are substituting for or interfering with appropriate MH and substance abuse treatment.
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Similar to mu opioid receptors, kappa and delta opioid receptors reside in the periphery, the dorsal root ganglion, the spinal cord, and in supraspinal regions associated with pain modulation. Both delta and kappa opioid agonists have been shown to activate pain inhibitory pathways in the central nervous system. Yet, currently there are only a few pharmacologic agents that target kappa receptors, and none that target delta receptors. ⋯ Studies have shown that delta opioid agonists can provide relief of inflammatory pain and malignant bone pain. Meanwhile, peripherally restricted kappa opioid agonists have been developed to target kappa opioid receptors located on visceral and somatic afferent nerves for relief of inflammatory, visceral, and neuropathic chronic pain. The recently shown efficacy of these analgesics combined with a possible lower abuse potential and side effect burden than mu opioid receptor agonists makes delta and peripherally restricted kappa opioid receptor agonists promising targets for treating pain.
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Most of the opioids used in clinical practice exert their effects through mu opioid receptors. Yet, subtle but important pharmacological differences have been observed among the mu opioids. Their potency, effectiveness, and adverse effects can vary unpredictably among patients. ⋯ However, the differences in structure at the C-terminus influence the activation patterns of the mu opioids. In addition, a second series of variants has been isolated that involves alternative splicing at the N-terminus. Together, these sets of mu opioid receptor splice variants may help explain the clinical variability of the mu drugs among patients and provide insights into why it is so important to individualize therapy for every patient in pain.
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The peer-reviewed literature yields a plethora of examples of variability in patient's responses to medications. The rapidly progressing field of pharmacogenetics offers insight into the variation in responses observed clinically, and in particular for the variability observed among patients administered mu opioid analgesics. Genetic variation leads to interperson variability in drug absorption, distribution, metabolism, and excretion, processes that have an important impact on the observed efficacy and toxicity of a drug. ⋯ In the near future, pharmacogenetic approaches may be implemented to best predict which medicine from the outset may be most appropriate for an individual-the therapy with the most sustained efficacy and the best side effect profile. In the meantime, pharmacogenetic studies on mu opioid analgesics have provided a molecular foundation supporting opioid rotation in cases in which opioid therapy loses efficacy or becomes associated with intolerable side effects. As more pharmacogenetic research links specific polymorphisms to the pharmacologic effects of specific opioid analgesics, clinicians will continue to improve their understanding of how to prescribe these medications more effectively.