Pain
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Individuals with spinal cord injury (SCI) often have chronic pain, which may have a major impact on their quality of life. The purpose of this article is to present an update on the classification of SCI pain, recent advances in the understanding of underlying mechanisms, and current evidence-based treatment of SCI pain. ⋯ We need to improve preclinical assessment of pain-like behavior in central pain models, and improve the clinical assessment of pain and our understanding of the interaction with cognitive, emotional, and social factors. In future studies on mechanisms and treatment, we need to acknowledge the different phenotypes of chronic SCI pain.
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The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. ⋯ To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.
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There has been a tension between the needs of regulators and industry to demonstrate that interventions are effective and safe, and the needs of professionals to understand how well interventions will work for their patients, and patients to understand what might work for them as individuals. The custom has been to focus on statistical outcomes based on average results, but in-depth analysis based on outcomes obtained by individual patients demonstrates that few are average. ⋯ This changes how benefit and risk are seen; nonresponders should stop treatments that don't work and not, therefore, be exposed to risks, while responders have very large benefits to offset against rare but potentially serious harm. This alternative view, patient-centred and practice-orientated, has major implications for clinical practice, how and why we do clinical trials and how they are designed, how health economic evaluations are done, for decisions made by regulatory and other bodies, and for the theory and practice of evidence-based medicine.
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The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. ⋯ At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.
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The pain matrix is conceptualised here as a fluid system composed of several interacting networks. A nociceptive matrix receiving spinothalamic projections (mainly posterior operculoinsular areas) ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits. Transition from cortical nociception to conscious pain relies on a second-order network, including posterior parietal, prefrontal and anterior insular areas. ⋯ Neuropathic allodynia has been associated with enhancement of ipsilateral over contralateral insular activation and lack of reactivity in orbitofrontal/perigenual areas. Although lack of response of perigenual cortices may be an epiphenomenon of chronic pain, the enhancement of ipsilateral activity may reflect disinhibition of ipsilateral spinothalamic pathways due to depression of their contralateral counterpart. This in turn may bias perceptual networks and contribute to the subjective painful experience.