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The Avoidance-Endurance Fast-Screen (AEFS) is a 9-item self-report questionnaire that classifies patients with back pain into four activity-related subgroups, based on the avoidance-endurance model (AEM) of pain. The objective of this study was to translate the AEFS into Danish and investigate its discriminative abilities in a large, diverse patient sample.
Learn More >The association of migraine with vascular comorbidities is long-established. The contribution of the "traditional" cardiovascular risk factors to this connection remains unclear.
Learn More >Atopic dermatitis (AD) and allergic asthma are complex disorders with significant public health burden. This review provides an overview of the recent developments on Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse counterpart MrgprB2) as a potential candidate to target neuro-immune interaction in AD and allergic asthma.
Learn More >Cognitive dysfunction characterized by executive dysfunction and persistent attention function has been reported in patients with amyotrophic lateral sclerosis (ALS); however, it is unclear if this contributes to the pain processing deficits associated with the disease.
Learn More >Good health is positively related to children's educational outcomes, but relationships may not be causal. Demonstrating a causal influence would strongly support childhood and adolescent health as important for education policy. We applied genetic causal inference methods to assess the causal relationship of common health conditions at age 10 (primary/elementary school) and 13 (mid-secondary/mid-high school) with educational attainment at 16 and school absence at 14-16. Participants were 6113 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Exposures were symptoms of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depression, asthma, migraines and BMI. Genetic liability for these conditions and BMI was indexed by polygenic scores. In non-genetic, multivariate-adjusted models, all health conditions except asthma and migraines were associated with poorer attainment and greater school absence. School absence substantially mediated effects of BMI (39.9% for BMI at 13) and migraines (72.0% at 10), on attainment with more modest mediation for emotional and neurodevelopmental conditions. In genetic models, a unit increase in standardized BMI at 10 predicted a 0.19 S.D. decrease (95% CI: 0.11, 0.28) in attainment at 16, equivalent to around a 1/3 grade lower in all subjects, and 8.7% more school absence (95% CI:1.8%,16.1%). Associations were similar at 13. Genetic liability for ADHD predicted lower attainment but not more absence. Triangulation across multiple approaches supports a causal, negative influence on educational outcomes of BMI and ADHD, but not of ASD, depression, asthma or migraine. Higher BMI in childhood and adolescence may causally impair educational outcomes.
Learn More >: To investigate differences in frequent pain or headaches and associated neurobehavioral symptoms among men, women, and transgender individuals with and without a history of traumatic brain injury (TBI). : Community : English and Spanish-speaking adults (n = 2,862) with and without self-reported TBI : Cross-sectional study : Behavioral Assessment Screening Tool (BAST) subscales for Negative Affect, Substance Abuse, Executive Function, Fatigue, Impulsivity, and one item for experiencing "frequent pain or headache." : Women reported more pain than men. Women with a mild TBI (mTBI) more often reported frequent headaches/pain than woman in general or those with mTBI alone. Women reporting frequent headache/pain reported more negative affect and fatigue than men with comparable TBI history. Individuals identifying as transgender/other without TBI had higher negative affect and fatigue than both men and women without TBI. Individuals with mTBI and frequent headache/pain reported more executive function problems than those with mTBI without headache/pain. Pain and moderate/severe TBI were associated with more executive function problems in men and women, but more so for women. : Results suggest frequent headache/pain may differ between genders, particularly after mTBI. Pain, fatigue, executive function, and negative affect may be especially important in women's recovery from TBI.
Learn More >Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ and NMDA receptors, gap junctions and D-amino acid oxidase.
Learn More >Body-specific mental rotation is thought to rely upon internal representations of motor actions. Handedness is a source of distinctly different motor experience that shapes the development of such internal representations. Yet, the influence of handedness upon hand mental rotation has never been systematically evaluated. Five databases were searched for studies evaluating hand left/right judgement tasks in adults. Two independent reviewers performed screening, data extraction, and critical appraisal. Eighty-seven datasets were included, with 72 datasets pooled; all had unclear/high risk of bias. Meta-analyses showed that right-handers were faster, but not more accurate, than left-handers at hand mental rotation. A unique effect of handedness was found on performance facilitation for images corresponding to the dominant hand. Meta-analyses showed that right-handers were quicker at identifying images of right hands than left hands-a dominance advantage not evident in left-handers. Differing hand representations (more lateralised hand dominance in right-handers) likely underpin these findings. Given potential differences between hand preference and motor performance, future research exploring their distinct contributions to mental rotation is warranted.
Learn More >Preclinical models that assess "pain" in rodents typically measure increases in behaviors produced by a "pain stimulus." A large literature exists showing that kappa opioid receptor (KOR) agonists can decrease these "pain-stimulated behaviors" following many different pain stimuli. Despite showing apparent antinociceptive properties in these preclinical models, KOR agonists failed as analgesics in clinical trials. Recent studies that assessed decreases in behavior due to a pain stimulus show that KOR agonists are not effective in restoring these "pain-depressed behaviors" to normal levels, which agrees with the lack of effectiveness for KOR agonists in clinical trials. One current explanation for the failure of previous KOR agonists in clinical trials is that those agonists activated beta-arrestin signaling and that KOR agonists with a greater bias for G protein signaling will be more successful. However, neither G protein-biased agonists nor beta-arrestin-biased agonists are very effective in assays of pain-depressed behavior, which suggests that novel biased agonists may still not be effective analgesics. This review provides a concise account of the effectiveness of KOR agonists in preclinical models of pain-stimulated and pain-depressed behaviors following the administration of different pain stimuli. Based on the previous results, it may be appropriate to include both behaviors when testing the analgesic potential of KOR agonists.
Learn More >The kappa opioid receptor (KOR) has emerged as a promising therapeutic target for pain and itch treatment. There is growing interest in biased agonists that preferentially activate select signaling pathways downstream of KOR activation on the cellular level due to their therapeutic promise in retaining the analgesic and antipruritic effects and eliminating the sedative and dysphoric effects of KOR signaling on the physiological level. The concept of ligand-selective signaling includes that biased ligands promote KOR to selectively recruit one transducer or regulator protein over another, introducing bias into the signaling cascade at the very receptor-proximal level. Measuring agonist effects directly at the receptor has remained challenging and previous studies have focused on inferring agonist-selective KOR engagement with G protein relative to β-arrestin based on downstream signaling readouts. Here we discuss novel strategies to directly assess ligand-selective effects on receptor activation using KOR-interacting biosensors. The conformation-specific cytoplasmic biosensors are disconnected from the endogenous signaling machinery and provide a direct receptor-proxy readout of ligand effects in living cells. Receptor-biosensor interaction is ligand concentration dependent and can be used to determine relative ligand potency and efficacy. In addition, the biosensors reveal the existence of two dimensions of agonist bias in the cellular context: Firstly, agonists can selectively produce discrete protein-engaged KOR states and secondly, agonists can differ in the precise subcellular location at which they activate KOR. We discuss the value and the limitations of using orthogonal receptor-interacting biosensors in the quest to understand functional selectivity amongst KOR agonists in the cellular context.
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