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Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naive patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use.
Learn More >We want to investigate degenerative changes of white matter volume (WMV) and grey matter volume (GMV) in individuals after a spinal cord injury (SCI). Published studies of whole-brain voxel-based morphometry (VBM) comparing SCI patients with controls published between 2006 and March 1st, 2018 were collected by searching PubMed, Web of Science, and EMBASE databases. Voxel-wise meta-analyses of GMV and WMV differences between SCI patients and controls were performed separately using seed-based d mapping. Twelve studies with 12 GMV datasets and 9 WMV datasets yielded a total of 466 individuals (190 SCI patients and 276 controls) that were included in this meta-analysis. Compared with controls, SCI patients showed GMV atrophy in sensorimotor system regions including the bilateral sensorimotor cortex (S1 and M1), the supplementary motor area (SMA), paracentral gyrus, thalamus, and basal ganglia, as well as WMV loss in the corticospinal tract. GMV aberrancies were also demonstrated in brain regions responsible for cognition and emotion, such as the orbitofrontal cortex (OFC) and the left insula. Additionally, GMV in both the bilateral S1 and the left SMA was positively correlated with the time span after the injury. Anatomical atrophy in cortical-thalamic-spinal pathways suggested that SCIs may result in degenerative changes of the sensorimotor system. Furthermore, OFC and insula GMV abnormalities may explain symptoms such as neuropathic pain and potential cognitive-emotional impairments in chronic SCI patients. These findings indicate that anatomical brain magnetic resonance imaging (MRI) protocols could be neuroimaging biomarkers for interventional studies and treatments.
Learn More >Previous studies have demonstrated important associations between personal resources and pain interference. Using latent profile analysis, the present study (a) identified subgroups of individuals with chronic pain who have different personal resource profiles; (b) explored sociodemographic differences among subgroups; and (c) examined how these subgroups differ in pain interference. Research Method/Design: Study 1 is based on daily diary and survey data from 220 individuals with fibromyalgia (FM). Study 2 is based on 4 annual surveys of 483 individuals with long-term neurological/neuromuscular disease or injury, and chronic pain. Modifiable personal resource variables including sense of resilience, social support, pain acceptance, and sleep quality were included in latent profile analyses.
Learn More >Antidepressant medications offer an effective treatment for depression, yet nearly 50% of patients either do not respond or have side-effects rendering them unable to continue the course of treatment. Mechanistic studies might help advance the pharmacology of depression by identifying pathways through which treatments exert their effects. Toward this goal, we aimed to identify the effects of antidepressant treatment on neural connectivity, the relationship with symptom improvement, and to test whether these effects were reproducible across two studies.
Learn More >This study investigated whether local intramuscular injection of non-psychoactive cannabinoids, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC) and their combinations can decrease nerve growth factor (NGF)-induced masticatory muscle sensitization in female rats.
Learn More >Vasculitic peripheral neuropathy (VPN) arises from an inflammatory obstruction in the blood vessels supplying peripheral nerves and subsequent ischemic insults, which exhibits the clinical features of neuropathic pain and impaired peripheral nerve function. VPN induced by ischemia-reperfusion (IR) has been reported to involve nuclear factor-κB (NF-κB)-mediated neuroinflammation. Recent studies have suggested that endoplasmic reticulum (ER) stress has been implicated in the development of peripheral neuropathies. Resveratrol possesses a potent anti-inflammatory capacity. We hypothesized that resveratrol may exert a protective effect against VPN through modulating the interrelated ER stress and NF-κB pathways. Male Sprague-Dawley rats were allocated into 5 groups: sham, sham + resveratrol 40 mg/kg (R40), IR, IR + R20 and IR + R40. VPN was induced by occluding the right femoral artery for 4 hours followed by reperfusion. Our data has shown that VPN induced by IR led to hind paw mechanical allodynia, heat hyperalgesia, and impaired motor nerve conduction velocity (MNCV). With resveratrol intervention, the behavioral parameters were improved in a dose-dependent manner and the MNCV levels were increased as well. The molecular data revealed that VPN induced by IR significantly increased the expression of NF-κB as well as the ER stress sensor proteins, protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 and activating transcription factor 6 in the sciatic nerves. More importantly, resveratrol significantly attenuated the expression of NF-κB and the ER stress sensor proteins after IR. In conclusion, resveratrol alleviates VPN induced by IR. The mechanisms may involve modulating NF-κB-mediated neuroinflammation via suppressing ER stress. This article is protected by copyright. All rights reserved.
Learn More >The spinal cord dorsal horn is the first relay station of the neural network for processing somatosensory information. High-throughput recording methods facilitate the study of sensory coding in the cortex but have not been successfully applied to study spinal cord circuitry until recently. Here, we review the development of the in vivo two-photon spinal calcium imaging preparation and biological findings from the first systematic characterization of the spinal response to cutaneous thermal stimuli, focusing on the difference between the coding of heat and cold, and the contribution of different peripheral inputs to thermosensory response in the spinal cord. Here we also report that knockout of TRPV1 channel impairs sensation of warmth, and somatostatin- and calbindin2-expressing neurons in the spinal dorsal horn preferentially respond to heat. Future work combining this technology with genetic tools and animal models of chronic pain will further elucidate the role of each neuronal type in the spinal thermosensory coding and their plasticity under pathological condition.
Learn More >Inhibitory glycinergic transmission in adult spinal cord is primarily mediated by glycine receptors (GlyRs) containing the α1 subunit. Here, we found that α1ins, a longer α1 variant with 8 amino acids inserted into the intracellular large loop (IL) between transmembrane (TM)3 and TM4 domains, was expressed in the dorsal horn of the spinal cord, distributed at inhibitory synapses, and engaged in negative control over nociceptive signal transduction. Activation of metabotropic glutamate receptor 5 (mGluR5) specifically suppressed α1ins-mediated glycinergic transmission and evoked pain sensitization. Extracellular signal-regulated kinase (ERK) was critical for mGluR5 to inhibit α1ins. By binding to a D-docking site created by the 8-amino-acid insert within the TM3-TM4 loop of α1ins, the active ERK catalyzed α1ins phosphorylation at Ser380, which favored α1ins ubiquitination at Lys379 and led to α1ins endocytosis. Disruption of ERK interaction with α1ins blocked Ser380 phosphorylation, potentiated glycinergic synaptic currents, and alleviated inflammatory and neuropathic pain. These data thus unraveled a novel, to our knowledge, mechanism for the activity-dependent regulation of glycinergic neurotransmission.
Learn More >Migraine is a common and severely disabling neurological disorder affecting millions of patients in Europe. Despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains poor, which is often attributed to a low availability of headache specialists. The aim of this study was to investigate the adherence to national guidelines and to assess the possible potential of optimized therapy regimens in migraine patients.
Learn More >Fibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with the brain through the enteric nervous system (ENS); its disruption has been associated with psychiatric and gastrointestinal disorders. To gain an insight into the pathogenesis of fibromyalgia and identify diagnostic biomarkers, we combined different omics techniques to analyse microbiome and serum composition.
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