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During the coronavirus 2019 (COVID-19) pandemic youth with chronic pain have experienced additional barriers to accessing treatment and managing their pain. This study explored the experiences of youth with chronic pain and their parents during the COVID-19 pandemic. Individual semi-structured interviews were conducted with 20 youth with chronic pain (aged 13-20 years) and one of their parents, recruited from a tertiary level pediatric chronic pain program. Interviews occurred between the months of June-August 2020 and enabled participants to describe their experiences of the COVID-19 pandemic according to their own unique perspectives. Transcripts were analysed using inductive reflexive thematic analysis. Four themes were generated and labelled: 'temporality, mental health, and pain', 'coping with pain during a global pandemic', 'impact on care', and 're-appraisal in the context of development and pandemic life'. Across these themes, youth and parents described their unique challenges of living with pain as they adapted to changing circumstances of the COVID-19 pandemic. Notably, youth experienced increased difficulties managing their mental health and pain, which were intricately connected and related to social isolation, temporality, and uncertainty exacerbated by the COVID-19 pandemic. Restrictions due to the COVID-19 pandemic impacted youth's access to care and their abilities to engage in coping strategies to manage their pain. The COVID-19 pandemic was also perceived to have interrupted youth's development and growing autonomy, prompting youth to re-appraise their current circumstances and imagined futures. Perspective: This manuscript provides an in-depth understanding of the impact of the COVID-19 pandemic on youth with chronic pain and their parents. Youth and their parents perceived the COVID-19 pandemic to have impacted youth's mental health, pain, socio-emotional development, and access to care.
Learn More >We evaluated different pain profiles as prospective predictors of multisite pain in 13-year-old adolescents (1300 girls and 1457 boys) enrolled in Generation XXI, a birth cohort study in Portugal.
Learn More >Ephrin B/EphB signaling pathway is involved in the regulation of pain caused by spinal cord injury. However, the role of ephrin-B3/EphBs signaling in regulation of nociceptive information is poorly understood. In the present study, formalin-induced inflammatory pain, mechanical allodynia and thermal hyperalgesia was measured using Efnb3 mutant mice (Efnb3 ) and wild-type (Efnb3 ) mice. The spinal cord (L4-6) was selected for molecular and cellular identification by western blotting and immunofluorescence. Efnb3 mutant mice showed a significant increased the thermal and mechanical threshold, followed by aberrant thin myelin sheath. Furthermore, expression of proteolipid protein (PLP) was significantly lower in L4-6 spinal cord of Efnb3 mice. These morphological and behavioral abnormalities in mutant mice were rescued by conditional knock-in of wild-type ephrin-B3. Intrathecal administration of specific PLP siRNA significantly increased the thermal and mechanical threshold hyperalgesia in wild-type mice. However, overexpressing PLP protein by AAV9-PLP could decrease the sensitivity of mice to thermal and mechanical stimuli in Efnb3 mice, compared with scrabble Efnb3 mice. Further, Efnb3 mice, which have activities to initiate forward signaling, but transduce reverse signals by ephrin-B3, shows normal acute pain behavior, compared with wild type mice. These findings indicate that a key molecule Efnb3 act as a prominent contributor to hyperalgesia and essential roles of ephrin-B3/EphBs in nociception through a myelin-mediated mechanism.
Learn More >Previous epidemiological studies have found an increased risk for ischemic stroke in patients with migraine; however, the evidence for a causal relationship between migraine and ischemic stroke is scarce. This study aims to explore the potential causal relationship between migraine and ischemic stroke and its subtypes [including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES)].
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. PECS-101, administered after the end of treatment with PTX, did not reverse mechanical allodynia. However, PECS-101 (1 mg/kg) administered along with PTX treatment caused a long-lasting relief of the mechanical and cold allodynia. These effects were blocked by a PPARγ, but not CB1 and CB2 receptor antagonists. Notably, the effects of PECS-101 on the relief of PTX-induced mechanical and cold allodynia were not found in macrophage-specific PPARγ-deficient mice. PECS-101 also decreased PTX-induced increase in Tnf, Il6, and Aif1 (Iba-1) gene expression in the DRGs and the loss of intra-epidermal nerve fibers. PECS-101 did not alter motor coordination, produce tolerance, or show abuse potential. In addition, PECS-101 did not interfere with the chemotherapeutic effects of PTX. Thus, PECS-101, a new fluorinated CBD analog, could represent a novel therapeutic alternative to prevent mechanical and cold allodynia induced by PTX potentially through the activation of PPARγ in macrophages.
Learn More >Patient-Reported Outcomes (PROs) have been developed to numerically quantify disability, impact and quality of life. They have been widely used in migraine clinical trials. However, we still do not know which PRO more accurately reflects preventive treatment response from a patient's perspective or which one may help us with treatment decisions in clinical practice. They have been used to enforce the efficacy results in clinical trials and real-world evidence so far. The aim of this study was to analyze which PROM is (1) better correlated with all primary efficacy endpoints and (2) which one is better associated with treatment continuation with CGRP-mAbs at week-12, which is usually the moment when this decision is made.
Learn More >An imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules ("GABA+") using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time.
Learn More >To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Thirty healthy adults received atogepant 60 mg, sumatriptan 100 mg, or coadministered drugs. Primary end point was geometric mean ratios (GMRs) and 90% CIs of interventions for area under the plasma concentration-time curve from time 0 to t (AUC) or infinity (AUC) and peak plasma concentration (C). Atogepant GMRs for AUC and AUC versus with sumatriptan were within 90% CI 0.80-1.25, indicating no interaction; atogepant C was reduced by 22% (GMR: 0.78; 90% CI: 0.69-0.89) with sumatriptan. Sumatriptan GMRs for AUC, AUC and C versus with atogepant were within 90% CI 0.80-1.25. Atogepant with sumatriptan had no clinically relevant pharmacokinetic interactions.
Learn More >Calcitonin gene-related peptide receptor (CGRPR) is a heterodimer protein complex consisting of a class-B G protein-coupled receptor (GPCR) named calcitonin receptor-like receptor (CLR) and an accessory protein, receptor activity modifying protein type 1 (RAMP1). Here in this study, with several molecular modeling approaches and molecular dynamics (MD) simulations, the structural and dynamical effects of RAMP1 on the binding of small molecule CGRPR inhibitors (namely rimegepant and telcagepant) to the CGRPR extracellular ectodomain complex site (site 1) and transmembrane binding site (site 2) are investigated. Results showed that although these molecules stay stable at site 1, they can also bind to site 2, which may be interpreted as non-specificity of the ligands, however, most of these interactions at transmembrane binding site are not sustainable or are weak. Furthermore, to examine the site 2 for gepant binding, different in silico experiments (i.e., alanine scanning mutagenesis, SiteMap, ligand decomposition binding free energy analyses) are also conducted and the results confirmed the putative binding pocket (site 2) of the gepants at the CGRPRs.
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