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‘It becomes the new everyday life’ – experiences of chronic pain in everyday life of people with limb-girdle muscular dystrophy.

To investigate experiences and reflections on challenges in everyday life of people living with limb-girdle muscular dystrophy (LGMD) and chronic pain in order to improve rehabilitation services.

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Morphological and functional brain changes in chronic cancer-related pain: A systematic review.

The purpose of this study was to perform a systematic review of the available literature on morphological and functional brain changes measured by modern neuroimaging techniques in patients suffering from chronic cancer-related pain. A systematic search was conducted in PubMed, Embase, and Web of Science using different keyword combinations. In addition, a hand search was performed on the reference lists and several databases to retrieve supplementary primary studies. Eligible articles were assessed for methodological quality and risk of bias and reviewed by two independent researchers. The search yielded only four studies, three of which used MRI and one PET-CT. None of the studies measured longitudinal morphological (i.e., gray or white matter) changes. All studies investigated functional brain changes and found differences in specific brain regions and networks between patients with chronic cancer-related pain and pain-free cancer patients or healthy volunteers. Some of these alterations were found in brain networks that also show changes in non-cancer populations with chronic pain (e.g., the default mode network and salience network). However, specific findings were inconsistent, and there was substantial variation in imaging methodology, analysis, sample size, and study quality. There is a striking lack of research on morphological brain changes in patients with chronic cancer-related pain. Moreover, only a few studies investigated functional brain changes. In the retrieved studies, there is some evidence that alterations occur in brain networks also involved in other chronic non-cancer pain syndromes. However, the low sample sizes of the studies, finding inconsistencies, and methodological heterogeneity do not allow for robust conclusions.

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The Role of Pain Catastrophizing, Emotional Intelligence, and Pain Intensity in the Quality of Life of Cancer Patients with Chronic Pain.

Pain catastrophizing (PC) is a negative cognitive distortion to actual or anticipated pain. This study aims to investigate the relationship between pain catastrophizing, emotional intelligence, pain intensity, and quality of life (QoL) in cancer patients with chronic pain. Eighty-nine outpatients with chronic pain attending pain clinics and palliative care units were recruited. Participants were men (42.7%) and women (57.3%) with an average age of 56.44 years (SD = 14.82). Self-report psychological measures were completed, including a measure of emotional intelligence, a standard measure of PC, a scale assessing pain intensity, and a scale measuring QoL. The PC scale was found to assess three correlated yet different dimensions of pain catastrophizing (helplessness, magnification, and rumination). Moreover, as expected, patients with PC scale scores ≥ 30 had lower scores in functional QoL dimensions and higher scores in the fatigue, pain, and insomnia symptom dimensions. Regression analyses demonstrated that PC (B = - 0.391, p = 0.004), pain intensity (B = - 1.133, p < 0.001), and education (B = 2.915, p = 0.017) remained the only significant variables related to QoL, when controlling for demographic and clinical confounders. Regarding mediating effects, PC and pain intensity were jointly found to be significant mediators in the relationship between emotional intelligence and QoL. Results are discussed in the context of the clinical implications regarding interventions designed to improve cancer patients' quality of life and offer new insight, understanding, and evaluation targets in the field of pain management.

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Treatment with brodalumab is not associated with improved sleep problems in real-life patients with plaque psoriasis: Results of the ProLOGUE study.

Psoriasis impacts various aspects of patients' health-related quality of life and is associated with sleep problems. However, research discussing the associations between interleukin-17 blockage therapies and sleep problems in patients with psoriasis is insufficient. We aimed to assess the effectiveness of brodalumab in alleviating sleep problems in real-life patients with plaque psoriasis. This analysis was part of the single-arm, open-label, multicenter, prospective, cohort study, ProLOGUE (study period October 2017-March 2020), which involved Japanese patients with plaque psoriasis. Assessments included correlation of Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R) scores (Sleep Problems Index-II [SPI-II] and MOS Sleep-R subscale scores) with multiple patient-reported outcome scores and the Psoriasis Area and Severity Index (PASI) at baseline. Additionally, change from baseline in MOS Sleep-R scores was assessed at weeks 12 and 48 of brodalumab treatment. Seventy-three patients were enrolled (male 82.2%, median age 54.0 years). At baseline, the SPI-II score correlated with the Patient Health Questionnaire-8 score (Spearman correlation coefficient [ρ] = -0.474) and weakly correlated with the Itch Numeric Rating Scale (NRS; ρ = -0.366), Skin Pain NRS (ρ = -0.275), and all Treatment Satisfaction Questionnaire for Medication-9 domain scores (ρ = 0.270, ρ = 0.303, and ρ = 0.322 for effectiveness, convenience, and global satisfaction, respectively) but did not correlate with the PASI score. The SPI-II score and MOS Sleep-R subscale scores, except the Snoring score (p = 0.0319), did not significantly change from baseline to week 12 of brodalumab treatment. In conclusion, treatment with brodalumab did not improve overall sleep problems in real-life patients with plaque psoriasis, suggesting that sleep problems require attention in daily clinical practice (Japan Registry of Clinical Trials identifier, jRCTs031180037).

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The association between migraine and dementia – a national register-based matched cohort study.

Migraine and dementia, two major public health challenges, are associated, but more knowledge is needed to understand their relationship. Objectives of this study were to investigate 1) the association between non-self-reported measures of migraine and dementia, and whether dementia was associated with 2) migraine without aura (MO) and with aura (MA) in combination with migraine medication use, and 3) migraine severity operationalized as the number of migraine prescriptions.

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Astrocyte-microglia Interaction Through C3/C3aR Pathway Modulates Neuropathic Pain in Rats Model of CCI.

Neuropathic pain (NP) is the cardinal symptom of neural injury, and its underlying molecular mechanism needs further investigation. Complements, especially complement 3 (C3), are involved in the pathophysiology of many neurological disorders, while the specific role of C3 in NP is still obscure. In this study, we found that both C3 and its receptor C3aR were upregulated in the spinal dorsal horn in a rat chronic constriction injury (CCI) model. In addition, C3 was mainly detected in astrocytes, while C3aR was expressed in microglia and neuron. Intrathecal injection of C3 antibody and C3aR antagonist alleviated NP in CCI model together with reduced M1 polarization of microglia. Our finding suggested that blockade of the C3/C3aR pathway might be a novel strategy for NP.

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Functional connectivity response to acute pain assessed by fNIRS is associated with BDNF genotype in fibromyalgia: an exploratory study.

Fibromyalgia is a heterogenous primary pain syndrome whose severity has been associated with descending pain modulatory system (DPMS) function and functional connectivity (FC) between pain processing areas. The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism has been linked to vulnerability to chronic pain. In this cross-sectional imaging genetics study, we investigated fibromyalgia, the relationship between BDNF Val66Met heterozygous genotypes (Val/Met), and the functional connectivity (FC) response pattern to acute pain stimulus in the motor (MC) and prefrontal (PFC) cortex assessed by near-infrared spectroscopy (fNIRS) before and after a cold pressor test utilizing water (0-1 °C). Also, we assessed the relationship between this genotype with the DPMS function and quality of life. We included 42 women (Val/Val = 30; Val/Met = 12) with fibromyalgia, ages 18-65. The MANCOVA comparing Val/Met to Val/Val genotypes showed higher ΔFC between left(l)-PFC-l-MC (β = 0.357, p = 0.048), l-PFC-right(r)-PFC (β = 0.249, p = 0.012), l-PFC-r-MC (β = 0.226, p = 0.022), and l-MC-r-PFC (β = 0.260, p = 0.016). Val/Met genotypes showed higher efficiency of the DPMS and lower disability due to pain. Here we show that fibromyalgia patients carrying the Val/Met BDNF genotype presented an increased ΔFC across MC and PFC in response to acute pain associated with differences in acute pain perception and fibromyalgia symptoms.

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Cell-free therapy for canine osteoarthritis: Current evidence and prospects.

Osteoarthritis is a progressive degenerative disease affecting joints. It is associated with structural and functional changes that cause lameness and pain in dogs. Mesenchymal stem cells (MSCs) are considered an ideal therapeutic candidate for treating inflammatory musculoskeletal conditions due to their paracrine and immunomodulatory characteristics. They are delivered intravenously or as intra-articular injections for treating canine osteoarthritis. However, studies have confirmed that the osteoarthritic synovial fluid is cytotoxic to cultured MSCs. Therefore, intra-articular transplantation of viable MSCs should be considered counterproductive since it minimizes cellular viability. Similarly, the intravenous administration of MSCs limits the therapeutic effects on the organ of interest since most of the administered cells get trapped in the lungs. Therefore, cell-free therapeutic strategies such as conditioned media and extracellular vesicles (EVs) can potentially become the future of MSC-based therapy in managing canine osteoarthritis. It overcomes the limitations of MSC-based therapy, such as tumor differentiation, immunogenicity, and pulmonary embolization, and has advantages like low immunogenicity and off-shelf availability. In addition, they eliminate problems such as low cell survival, transmission of infections, and unpredictable behavior of the transplanted MSCs, thereby acting as a safe alternative to cell-based therapeutics. However, very limited data is available on the efficacy and safety of cell-free therapy using MSCs for managing canine osteoarthritis. Therefore, large-scale, multicentric, randomized clinical controlled trials are required to establish the therapeutic efficacy and safety of MSC-based cell-free therapy in clinical cases of canine osteoarthritis.

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Motor event-related synchronization as an inhibitory biomarker of pain severity, sensitivity, and chronicity in patients with knee osteoarthritis.

The study aimed to examine the clinical and neurophysiological predictors of motor event-related desynchronization (ERD) and synchronization (ERS) in patients with chronic pain due to knee osteoarthritis (KOA).

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Psychopathological profile and sagittal alignment in low-back pain.

Low-back pain requires comprehensive care using a biopsychosocial model. The psychologic dimension plays an important role, but the link between sagittal alignment and a given psychopathological profile is little studied. The aim of this study was to analyze the psychopathological profiles and sagittal parameters of a population with low-back pain and to assess the link.

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