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In recent years, long-term prescribing and use of strong opioids for chronic non-cancer pain (CNCP) has increased in high-income countries. Yet existing uncertainties, controversies and differing recommendations make the rationale for prolonged opioid use in CNCP unclear. This systematic review and meta-analyses (MAs) compared the efficacy, safety and tolerability of strong opioids with placebo/non-opioid therapy in CNCP, with a special focus on chronic low back pain (CLBP). Systematic literature searches were performed in four electronic databases (Medline, Web of Science, Cochrane Library and CINAHL) in July 2019 and updated by regular alerts until December 2020. We included 16 placebo-controlled RCTs for CLBP and five studies (2 RCTs and 3 non-randomized studies) of opioids vs non-opioids for CNCP in the quantitative and qualitative synthesis. Random effects pairwise MAs were performed for efficacy, safety and tolerability outcomes and subgroup analyses for treatment duration, study design, and opioid experience status. Very low- to low-certainty findings suggest that 4-15 weeks (short-/intermediate term) opioid therapy in CLBP (compared to placebo) may cause clinically relevant reductions in pain but also more gastrointestinal and nervous system adverse events (AEs), with likely no effect on disability. In contrast, long-term opioid therapy (≥ 6 months) in CNCP may not be superior to non-opioids in improving pain or disability/pain-related function, but seems to be associated with more AEs, opioid abuse/dependence, and possibly an increase in all-cause mortality. Our findings also underline the importance and need for well-designed trials assessing long-term efficacy and safety of opioids for CNCP and CLBP.
Learn More >Sleep problems and regular leisure time physical activity (LTPA) are interrelated and have contrasting effects on risk of back pain. However, no studies have investigated the influence of long-term poor sleep quality on risk of back-related disability, or if LTPA modifies this association. The study comprised data on 8601 people who participated in three consecutive surveys over ~ 22 years, and who reported no chronic back pain at the two first surveys. Adjusted risk ratios (RRs) for back-related disability were calculated at the last survey, associated with the joint effect of changes in sleep quality between the two first surveys and meeting physical activity guidelines at the second survey. Compared to people with long-term good sleep, people with long-term poor sleep had nearly twice the risk of back-related disability (RR 1.92, 95% CI 1.48-2.49). There was no statistical interaction between sleep and LTPA but people who reported long-term poor sleep and meeting the physical activity guidelines had 35% lower risk of back-related disability compared to people with same level of sleep problems, but who not met the guidelines. These findings suggest that long-term poor sleep quality contributes to a substantially increased risk of chronic and disabling back pain irrespective of LTPA.
Learn More >Neuronal calcium sensor 1 (NCS1), a calcium-binding protein, and transient receptor potential V4 (TRPV4), a plasma membrane calcium channel, are fundamental in the regulation of calcium homeostasis. The interactions of these proteins and their regulation by paclitaxel (PTX) were investigated using biochemical, pharmacological, and electrophysiological approaches in both a breast cancer epithelial cell model and a neuronal model. TRPV4 and NCS1 reciprocally immunoprecipitated each other, suggesting that they comprise a signaling complex. The functional consequence of this physical association was that TRPV4 currents increased with increased NCS1 expression. Calcium fluxes through TRPV4 correlated with the magnitude of TRPV4 currents and these calcium fluxes depended on NCS1 expression levels. Exposure to PTX amplified the acute effects of TRPV4 expression, currents, and calcium fluxes, but decreased the expression of NCS1. These findings augment the understanding of the properties of TRPV4, the role of NCS1 in the regulation of TRPV4, and the cellular mechanisms of PTX-induced neuropathy. TRPV4 and NCS1 physically and functionally interact. Increased expression of NCS1 enhances TRPV4 dependent currents, which are further amplified by treatment with the chemotherapeutic drug, paclitaxel, an effect associated with adverse effects of chemotherapy, including neuropathy.
Learn More >Opioids are still widely prescribed to long-term pain patients although they are no longer recommended for long-term treatments due to poor evidence for long-term efficacy, risks of serious side effects, and the possibility of inducing opioid hyperalgesia. In a Cochrane study from 2017, the authors identified an urgent need for more randomized controlled trials investigating the efficiency and effects of opioid tapering. The study aimed to assess (1) the efficiency of a structured intervention in causing stable reductions of opioid consumption in a population with long-term non-malignant pain and (2) effects on pain, pain cognitions, physical and mental health, quality of life, and functioning in response to opioid tapering.
Learn More >To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.
Learn More >Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe. We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation.
Learn More >Neuropathic pain (NP) is a clinical symptom that accompanies many diseases. We investigated the effect of receptor-interacting protein kinase 3 (RIP3)-regulated necroptosis on NP, and explore its relationship with microglia, in order to provide a theoretical basis for further research and provide new insights into the treatment of NP. In this study, the spared nerve injury (SNI) model was used along with intervention with necrostatin and the inhibitor of necroptosis necrostatin-1 (Nec-1). Pain behavior tests were performed 1 and 3 days before the nerve injury (or sham) operation, and on days 1, 3, 5, 7, 10 and 14 after the operation. The spinal cord tissues were collected for detection of RIP3 expression and distribution, changes in the number of microglia cells, activation of necroptosis, and the level of pro-inflammatory factors. Collected spinal cord tissues were analysed using western blot, immunohistochemistry, immunofluorescence, immunoprecipitation assays and ELISA, respectively. We found that, compared with the sham group, the expression of RIP3 protein in the spinal cord of rats in the SNI group increased from 3 days to 14 days after surgery. Immunofluorescence staining showed that RIP3 was co-expressed with the microglia and the number of microglia increased significantly in the SNI model group. The results of immunoprecipitation assays suggested that a RIP3-mediated necroptosis pathway promotes NP. After treatment with Nec-1, the expression of RIP3 protein and the number of microglia was significantly reduced, and the expression levels of TNF-α, IL-1β and IL-6 in spinal dorsal horns were significantly decreased. These results indicate that RIP3 promotes necroptosis to increase the occurrence of NP via microglia.
Learn More >Biofeedback is effective in treating migraines. It is believed to have a beneficial effect on autonomous nervous system activity and render individuals resilient to stressors that may trigger a migraine. However, widespread use of biofeedback is hampered by the need for a trained therapist and specialized equipment. Emerging digital health technology, including smartphones and wearables (mHealth), enables new ways of administering biofeedback. Currently, mHealth interventions for migraine appear feasible, but development processes and usability testing remain insufficient.
Learn More >Allergic inflammation is often the result of a dysregulated Th2 immune response, IgE production, and the release of allergic mediators such as histamine or leukotrienes (LTs) by basophils and mast cells (MCs). Allergic diseases can manifest as acute allergic reactions (anaphylaxis), or as chronic allergic inflammation in chronic urticaria, allergic rhinitis, allergic asthma, and atopic dermatitis (AD). Common allergic symptoms such as sneezing, airway mucus secretion, and chronic itch are caused by interactions between immune cells and sensory neurons in the inflamed tissue.
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