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Targeting the SHIP1 Pathway Fails to Show Treatment Benefit in Interstitial Cystitis/Bladder Pain Syndrome: Lessons Learned from Evaluating Potentially Effective Therapies in This Enigmatic Syndrome.

In this 12-week, randomized, double-blind, placebo controlled, multicenter, 3-arm, parallel group, phase 3 trial we assessed the effects of a novel SHIP1 activator on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome.

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Catechol-O-methyltransferase polymorphism Val158Met is associated with distal neuropathic pain in HIV-associated sensory neuropathy.

Many of those aging with HIV suffer from distal neuropathic pain (DNP) due to HIV-associated sensory neuropathy (HIV-SN). Prior studies have linked chronic pain conditions to a variant of the catechol-O-methyltransferase (COMT), ValMet. This variant confers reduced enzymatic activity and results in higher synaptic dopamine levels. Here we examined the role of ValMet as a predictor of DNP in HIV-SN.

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A Person-Centered Prehabilitation Program Based on Cognitive-Behavioral Physical Therapy for Patients Scheduled for Lumbar Fusion Surgery: A Randomized Controlled Trial.

Prehabilitation programs have led to improved postoperative outcomes in several surgical contexts, but there are presently no guidelines for the prehabilitation phase before lumbar fusion surgery.

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Central hypersensitivity – A model for persistent musculoskeletal pain in inflammatory bowel diseases.

Pain is reported to affect over 70% of individuals with inflammatory bowel diseases (IBD), with abdominal and musculoskeletal (MSK) pain representing the most common complaints. MSK pain is typically considered within the narrow framework of inflammatory extraintestinal manifestations of IBD, resulting in a limited scope for the nature and underlying mechanisms participating in MSK pain experiences in this population. Symptoms related to central sensitization have recently demonstrated association with active IBD and worse MSK pain experiences, suggesting a potential roll for central mechanisms in MSK-related pain. Current literature exploring persistent pain in chronic inflammatory and MSK populations propose complex pain models comprised of dynamic nervous system relationships influenced by primary disease features and concomitant pain states, as well as affective and cognitive components. Nervous system contributions in the development and maintenance of persistent pain are postulated to include mechanisms of peripheral and central sensitization, changes in descending central modulation, as well as structural brain changes. These models go beyond current MSK pain models described in IBD literature, highlighting the need for new frameworks for considering MSK-related pain in IBD. Consequently, this paper proposes a broader theoretical model whereby central mechanisms, such as central sensitization and grey matter changes, as well as psychological and disease factors are suggested to modulate pain experiences in this population. Exploration of relationships within the proposed framework may provide not only a deeper understanding of the generation and maintenance of persistent MSK pain in IBD, but also highlight the need for new targeted management pathways in this population. This paper hypothesizes that exploration of central sensitization in IBD patients will demonstrate altered somatosensory functioning in patients with MSK pain, and that IBD activity and psychological factors will be associated with altered somatosensory functioning and worse pain experiences.

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Pharmacological interventions for chronic pain in children: an overview of systematic reviews.

We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

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American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives.

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.

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Specific brain morphometric changes in spinal cord injury: a voxel-based meta-analysis of white and grey matter volume.

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.

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Personal resource profiles of individuals with chronic pain: Sociodemographic and pain interference differences.

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.

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The association between antidepressant treatment and brain connectivity in two double-blind, placebo-controlled clinical trials: a treatment mechanism study.

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.

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Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain.

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.

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