Pain
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Although multimodal management of chronic noncancer pain (CNCP) is recommended, long-term treatment utilization patterns among people using opioids are not well known. The Pain and Opioids IN Treatment study recruited Australian adults receiving opioids for CNCP for more than 6 weeks from community pharmacies. Pharmacological (opioid and nonopioid analgesics and psychotropic medicines) and nonpharmacological (physical, mental health, and specialized) treatments used in the previous 12 months and 30 days were collected annually over 4 years (2015-2018). ⋯ This study demonstrates that many Australians taking opioids long-term for CNCP also use nonopioid pharmacological and nonpharmacological treatments. The use of pharmacological treatments including nonsteroidal anti-inflammatory drugs, psychotropic medicines, and gabapentinoids, outside guidelines, warrants review. Furthermore, despite Australia's universal healthcare scheme subsidising some nonpharmacological treatments, overall use of these treatments was associated with having private health insurance, highlighting a need for more equitable service provision.
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Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. Although the development of chronic pain is moderately heritable, how disease-related alterations at the microscopic genetic architecture drive macroscopic brain abnormalities is currently largely unknown. Here, we examined alterations in morphometric similarity (MS) and applied an integrative imaging transcriptomics approach to identify transcriptional and cellular correlates of these MS changes, in 3 independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain, and fibromyalgia) and age-matched and sex-matched pain-free controls. ⋯ By leveraging transcriptomic data from Allen Human Brain Atlas, we show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes related to pain and broadly involved in the glial immune response and neuronal plasticity. Our findings bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of chronic pain. Although correlational, our data suggest that cortical remodelling in chronic pain might be shaped by multiple elements of the cellular architecture of the brain and identifies several pathways that could be prioritized in future genetic association or drug development studies.
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Mean pain intensity alone is insufficient to describe pain phenotypes in sickle cell disease (SCD). The objective of this study was to determine impact of day-to-day intraindividual pain variability on patient outcomes in SCD. We calculated metrics of pain variability and pain intensity for 139 participants with <10% missing data in the first 28 days of the Pain in Sickle Cell Epidemiology Study. ⋯ Cluster 2 included individuals with the highest mean pain, highest temporal dependency, highest proportion of days with pain and opioid use, and lowest physical function. Cluster 3 included individuals with high levels of mean pain, highest temporal instability, but with lower temporal dependency, proportion of days with pain and opioid use, and physical function compared with cluster 2. We conclude that intraindividual pain variability is associated with patient outcomes and psychological characteristics in SCD and is useful in delineating phenotypes of pain in SCD.
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Identifying the genetic determinants of pain is a scientific imperative given the magnitude of the global health burden that pain causes. Here, we report a genetic screen for nociception, performed under the auspices of the International Mouse Phenotyping Consortium. A biased set of 110 single-gene knockout mouse strains was screened for 1 or more nociception and hypersensitivity assays, including chemical nociception (formalin) and mechanical and thermal nociception (von Frey filaments and Hargreaves tests, respectively), with or without an inflammatory agent (complete Freund's adjuvant). ⋯ Two of the 13 genes (Gria1 and Htr3a) have been previously reported with nociception-related phenotypes in genetically engineered mouse strains and represent useful benchmarking standards. One of the 13 genes (Cnrip1) is known from human studies to play a role in pain modulation and the knockout mouse reported herein can be used to explore this function further. The remaining 10 genes (Abhd13, Alg6, BC048562, Cgnl1, Cp, Mmp16, Oxa1l, Tecpr2, Trim14, and Trim2) reveal novel pathways involved in nociception and may provide new knowledge to better understand genetic mechanisms of inflammatory pain and to serve as models for therapeutic target validation and drug development.
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We modelled the effects of pain intensity inclusion thresholds (3/10, 4/10, and 5/10 on a 0- to 10-point numerical pain rating scale) on the magnitude of the regression to the mean effect under conditions that were consistent with the sample mean and variance, and intermeasurement correlation observed in clinical trials for the management of chronic pain. All data were modelled on a hypothetical placebo control group. We found a progressive increase in the mean pain intensity as the pain inclusion threshold increased, but this increase was not uniform, having an increasing effect on baseline measurements compared with study endpoint measurements as the threshold was increased. ⋯ At its smallest, the regression to the mean effect was 0.13/10 (95% confidence interval: 0.03/10-0.24/10; threshold: 3/10, baseline mean pain: 6.5/10, SD: 1.6/10, and correlation: 0.44), and at its greatest, it was 0.78/10 (95% confidence interval: 0.63/10-0.94/10; threshold: 5/10, baseline mean pain: 6/10, SD: 1.8/10, and correlation: 0.19). We have shown that using pain inclusion thresholds in clinical trials drives progressively larger regression to the mean effects. We believe that a threshold of 3/10 offers the best compromise between maintaining assay sensitivity (the goal of thresholds) and the size of the regression to the mean effect.