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(1) Background: Research has shown that thoughts about pain are important for the management of chronic pain in children. In order to monitor changes in thoughts about pain over time and evaluate the efficacy of treatments, we need valid and reliable measures. The aims of this study were to develop a questionnaire to assess a child's concept of pain and to evaluate its psychometric properties; (2) Methods: This is a cross-sectional, two-phase, mixed-method study. A total of 324 individuals aged 8 to 17 years old responded to the newly created questionnaire. The Conceptualization of Pain Questionnaire (COPAQ) was calibrated using the Rasch model. The chi-square test was used for the fit statistics. Underfit and overfit of the model were determined and a descriptive analysis of infit and outfit was conducted to identify who responded erratically. Internal consistency was measured using the Person Separation Index (PSI); (3) Results: Fit to the Rasch model was good. Suitable targeting indicated which items were simple to answer; Person Fit identified 9.56% children who responded erratically; PSI = 0.814; (4) Conclusions: The findings suggest that COPAQ is a measure of a child's concept of pain that is easy to administer and respond to. It has a good fit and a good internal consistency.
Learn More >Overlap of pathways enriched by single nucleotide polymorphisms and DNA-methylation underlying chronic postsurgical pain (CPSP), prompted pilot study of CPSP-associated methylation quantitative trait loci (meQTL). Children undergoing spine-fusion were recruited prospectively. Logistic-regression for genome- and epigenome-wide CPSP association and DNA-methylation-single nucleotide polymorphism association/mediation analyses to identify meQTLs were followed by functional genomics analyses. CPSP (n = 20/58) and non-CPSP groups differed in pain-measures. Of 2753 meQTLs, DNA-methylation at 127 cytosine-guanine dinucleotides mediated association of 470 meQTLs with CPSP (p < 0.05). At PARK16 locus, CPSP risk meQTLs were associated with decreased DNA-methylation at and increased DNA-methylation at Corresponding blood eQTLs (GTEx) and cytosine-guanine dinucleotide-loci enrichment for histone marks, transcription factor binding sites and ATAC-seq peaks suggest altered transcription factor-binding. CPSP-associated meQTLs indicate epigenetic mechanisms mediate genetic risk. Clinical trial registration: NCT01839461, NCT01731873 (ClinicalTrials.gov).
Learn More >Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described. GDC-0334 inhibited TRPA1 function on airway smooth muscle and sensory neurons, decreasing edema, dermal blood flow (DBF), cough, and allergic airway inflammation in several preclinical species. In a healthy volunteer Phase 1 study, treatment with GDC-0334 reduced TRPA1 agonist-induced DBF, pain, and itch, demonstrating GDC-0334 target engagement in humans. These data provide therapeutic rationale for evaluating TRPA1 inhibition as a clinical therapy for asthma.
Learn More >Given the potential for obesity to complicate migraine treatment outcomes, there is a need to understand patterns and correlates of acute medication use among individuals with this comorbidity. Experience sampling methodology (ESM) was used to characterize patterns of acute medication use among those with migraine and overweight/obesity and to examine individual and momentary factors related to medication use (both migraine-specific and nonspecific medications). Women with migraine and overweight/obesity (N = 170) seeking behavioral migraine treatment completed questionnaires followed by 28 days of daily ESM headache diaries. Participants used medications to treat 71.9% of attacks, 20% of which were treated with migraine-specific medications. Participants were more likely to use medication in the context of longer and more severe attacks that started earlier in the day. Presence of aura and greater work-related pain interference uniquely related to migraine-specific medication use. Questionnaire-assessed factors were not related to medication use, although older age and higher educational attainment related to more frequent use. A substantial proportion of attacks were left untreated, suggesting unmet treatment needs in this population. Results also suggest that ESM-assessed factors are more salient correlates of medication use compared to questionnaires. Additional investigation of barriers to medication use is needed.
Learn More >Clinical models of chronic low back pain (cLBP) highlight the role of excessive attention to pain and kinesiophobia on the origin of disability. At the motor control level, various mechanisms are involved in the impairments observed in patients with cLBP. We aimed to assess the role of maladaptative attentional behaviors by using a complex systems approach and a visual display as a distraction during walking. Sixteen patients with cLBP with no previous surgery or significant leg pain and 16 healthy matched controls were included. Patients walked on a treadmill at preferred walking speed with and without distraction. Stride time (ST) fractal complexity was assessed using detrended fluctuation analysis. A two-way analysis of variance with repeated measures on distraction was performed on fractal exponents. We found a significant group × distraction interaction effect on fractal complexity of ST series (F(1,30) = 9.972, P = 0.004). Post hoc analysis showed that, without distraction, patients with cLBP had significantly lower ST complexity than controls, but when distracted, they regained gait complexity, recovering the level of controls. Our results suggest that excessive attention to pain causes loss of complexity and adaptability in cLBP and explain alterations of motor control with pain. Fractal analysis seems to be a promising method to explore movement variability and individual adaptability in musculoskeletal disorders.
Learn More >To evaluate the impact of two calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant.
Learn More >Migraine has been associated with many comorbidities. However, lifestyle factors and the presence of comorbid diseases have not previously been extensively studied in the same sample. This study aimed to compare the prevalence of unhealthy lifestyle factors and comorbid diseases between patients with migraine and migraine-free controls with subgroup analyses to determine the pathophysiology and possible consequences.
Learn More >Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments.
Learn More >The need for measuring emotional functioning in chronic pain patients was recognized decades ago. The Initiative on Methods, Measures, and Pain Assessment in Clinical Trials (IMMPACT) proposed the Profile of Mood States (POMS) for this purpose. However, to date, its factor structure has not been confirmed in these patients.
Learn More >The novel coronavirus disease (COVID-19) has caused prolonged disruptions in daily life for many communities. Little is known about the impact of the COVID-19 pandemic on the health and well-being of youth with chronic pain and their families. We conducted a longitudinal, mixed-methods study to characterize early adaptation to the COVID-19 pandemic among 250 families of youth (ages 12-21 years) diagnosed with chronic headache (64%) or other chronic pain conditions (36%) and to determine whether direct exposures to COVID-19 and secondary economic stress modified symptom trajectories. Youth and parents reported on pain interference, anxiety, depression, and insomnia symptoms at 4 waves of data collection from April 2020 to July 2020. We also collected qualitative data on the impact of the pandemic on the youth's pain problem. Nearly half of our sample (49.6%) experienced direct exposures to COVID-19. Secondary economic stress was also common, affecting 44.4% of families. Symptom trajectories for pain, insomnia, depression, and anxiety remained stable or improved for most participants, indicating adaptive adjustment. However, overall symptom burden was high with persistent and clinically elevated depression, anxiety, and insomnia symptoms common among youth and parents. Direct exposures to COVID-19 did not modify symptom trajectories. However, youth pain interference and parent insomnia worsened in families who experienced secondary economic stress. Qualitative data revealed perceived benefits and harms from school closures on the youth's pain problem. Our findings of high symptom burden suggest that pediatric pain clinicians should offer distance assessment and treatment (eg, through telemedicine) to avoid pandemic-related disruptions in pain care.
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