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Disease Mechanisms in Atopic Dermatitis: A Review of Aetiological Factors.

Atopic dermatitis is a prevalent inflammatory skin condition characterized by itch and dry skin, which affects 15-20% of children and 3-5% of adults. This article reviews epidemiological, clinical and experimental data to provide an overview of the most important disease mechanisms in atopic dermatitis. Genetic predisposition, environmental insults, atopic triggers, complex host immune response and skin barrier changes, and altered skin microbiota are discussed. Whilst our understanding of atopic dermatitis has improved dramatically in recent years, many basic aspects are still not understood. Further research is needed to fully understand this complex skin disease.

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COVID-19 is a Real Headache!

After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporo-parietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.

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Benefits and Harms of Electrical Neuromodulation for Chronic Pelvic Pain: A Systematic Review.

Patients with chronic pelvic pain (CPP) may have pain refractory to conventional pain management strategies. Neuromodulation could provide relief of pain.

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The sodium channel Nav1.7 is involved in paclitaxel-induced peripheral neuropathy though ERK1/2 signaling in rats.

Paclitaxel treatment is a major cause of chemotherapy-induced peripheral neuropathy. The sodium channel Nav1.7 plays a critical role in pain perception. However, whether Nav1.7 in the dorsal root ganglion (DRG) is involved in paclitaxelinduced peripheral neuropathy remains unclear. Thus, our study aimed to evaluate whether Nav1.7 participates in the pathogenesis of paclitaxel-induced neuropathy.

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Does intensive interdisciplinary pain treatment improve pediatric headache-related disability?

To examine the effectiveness of intensive interdisciplinary pain treatment for improving disability in children with chronic headache using the International Classification of Functioning, Disability and Health model as a conceptual framework for disability assessment. Children with chronic headache ( = 50; ages 10-19 years; 62% female) attended an intensive interdisciplinary pain treatment program 8 h/day, 5 times/week for 2-7 weeks. Disability measures were administered at admission, discharge, and 6-8 week follow-up. Disability outcomes were analyzed retrospectively. Wilcoxon signed rank tests and Friedman's analyses of variance were used to compare scores across two and three longitudinal time points, respectively. After rehabilitation, disability reduced on the Headache Impact Test-6 from severe impact at admission to some impact at follow-up ( < 0.001). Median time on the modified Bruce protocol increased from 13.1 min (interquartile range = 12.6-14.1) to 14.4 min (interquartile range = 12.9-16.3),  < 0.001, with gains maintained at follow-up. Improvements in pain and disability were associated with improvements in school participation. Findings of this study support the effectiveness of intensive interdisciplinary pain treatment for improving disability in children with chronic headache.Implication for rehabilitationIntensive interdisciplinary pain treatment is effective for improving pain and disability in children with chronic headaches.Application of the ICF model to disability assessment suggests that children with chronic headaches may experience significant disability, even when standardized assessments of physical capacity are normal.The modified Bruce protocol, Pediatric Evaluation of Disability Inventory – Computerized Adaptive Tests, and Headache Impact Test-6 appear particularly valuable in understanding the nature of disability in children with chronic headaches.

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Pain-Evoked Reorganization in Functional Brain Networks.

Recent studies indicate that a significant reorganization of cerebral networks may occur in patients with chronic pain, but how immediate pain experience influences the organization of large-scale functional networks is not yet well characterized. To investigate this question, we used functional magnetic resonance imaging in 106 participants experiencing both noxious and innocuous heat. Painful stimulation caused network-level reorganization of cerebral connectivity that differed substantially from organization during innocuous stimulation and standard resting-state networks. Noxious stimuli increased somatosensory network connectivity with (a) frontoparietal networks involved in context representation, (b) "ventral attention network" regions involved in motivated action selection, and (c) basal ganglia and brainstem regions. This resulted in reduced "small-worldness," modularity (fewer networks), and global network efficiency and in the emergence of an integrated "pain supersystem" (PS) whose activity predicted individual differences in pain sensitivity across 5 participant cohorts. Network hubs were reorganized ("hub disruption") so that more hubs were localized in PS, and there was a shift from "connector" hubs linking disparate networks to "provincial" hubs connecting regions within PS. Our findings suggest that pain reorganizes the network structure of large-scale brain systems. These changes may prioritize responses to painful events and provide nociceptive systems privileged access to central control of cognition and action during pain.

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The Effect of Pain Resilience on Experimental Pain Experience Across Different Stimuli.

Pain resilience, one's ability to maintain behavioral engagement and adaptively regulate cognitions and emotions despite intense or prolonged pain, has been shown to protect against negative pain-related outcomes in experimental settings. A weakness of this research, and much of experimental pain research in general, has been the lack of rationale behind the selection of noxious stimuli which can activate different nociceptive fibers. The present study sought to determine if the relationship between pain resilience and pain ratings differed across stimuli based on the stimulated nociceptors.

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Is Preoperative Quantitative Sensory Testing Related to Persistent Postsurgical Pain? A Systematic Literature Review.

Persistent postsurgical pain (PPSP) is a common complication of surgery that significantly affects quality of life. A better understanding of which patients are likely to develop PPSP would help to identify when perioperative and postoperative pain management may require specific attention. Quantitative sensory testing (QST) of a patient'fs preoperative pain perception is associated with acute postoperative pain, and acute postoperative pain is a risk factor for PPSP. The direct association between preoperative QST and PPSP has not been reviewed to date. In this systematic review, we assessed the relationship of preoperative QST to PPSP. We searched databases with components related to (1) preoperative QST; (2) association testing; and (3) PPSP. Two authors reviewed all titles and abstracts for inclusion. Inclusion criteria were as follows: (1) QST performed before surgery; (2) PPSP assessed ≥3 months postoperatively; and (3) the association between QST measures and PPSP is investigated. The search retrieved 905 articles; 24 studies with 2732 subjects met inclusion criteria. Most studies (22/24) had moderate to high risk of bias in multiple quality domains. Fourteen (58%) studies reported a significant association between preoperative QST and PPSP. Preoperative temporal summation of pain (4 studies), conditioned pain modulation (3 studies), and pressure pain threshold (3 studies) showed the most frequent association with PPSP. The strength of the association between preoperative QST and PPSP varied from weak to strong. Preoperative QST is variably associated with PPSP. Measurements related to central processing of pain may be most consistently associated with PPSP.

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A novel pyrazole-containing selenium compound modulates the oxidative and nitrergic pathways to reverse the depression-pain syndrome in mice.

Bearing in mind that pain and major depressive disorder (MDD) often share biological pathways, this condition is classified as depression-pain syndrome. Mounting evidence suggests that oxidative stress is implicated in the pathophysiology of this syndrome. The development of effective pharmacological interventions for the depression-pain syndrome is of particular importance as clinical treatments for this comorbidity have shown limited efficacy. Therefore, the present study aimed to evaluate whether the 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) was able to reverse the depression-pain syndrome induced by intracerebroventricular (i.c.v) streptozotocin (STZ) in mice and the possible modulation of oxidative and nitrergic pathways in its effect. The treatment with SePy (1 and 10 mg/kg) administered intragastrically (i.g.) reversed the increased immobility time in the tail suspension test, decreased grooming time in the splash test, latency time to nociceptive response in the hot plate test, and the response frequency of Von Frey hair (VFH) stimulation induced by STZ (0.2 mg/4 μl/per mouse). Additionally, SePy (10 mg/kg, i.g.) reversed STZ-induced alterations in the levels of reactive oxygen species, nitric oxide, and lipid peroxidation and the superoxide dismutase and catalase activities in the prefrontal cortices (PFC) and hippocampi (HC) of mice. Treatment with SePy (10 mg/kg, i.g.) also reversed the STZ-induced increased expression of inducible nitric oxide synthase (iNOS) and glycogen synthase kinase 3 beta (GSK3β) in the PFC and HC. An additional molecular docking investigation found that SePy binds to the active site of iNOS and GSK3β. Altogether, these results indicate that the antidepressant-like effect of SePy is accompanied by decreased hyperalgesia and mechanical allodynia, which were associated with its antioxidant effect.

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Lessons for Better Pain Management in the Future: Learning from the Past.

The treatment of noncancer pain in the United States and globally is met with significant challenges, resulting in profound physical, emotional, and societal costs. Based on this need, numerous modalities have been proposed to manage chronic pain, including opioid and nonopioid interventions as well as surgical approaches. Thus, the future of pain management continues to be mired in evolving concepts and constant debates. Consequently, it is crucial to understand the past as we move towards the future. The evolution of lessons for better pain management at present and for the future starting from the 1990s to the present date are reviewed and emphasized with a focus on learning from the past for the future. This review summarizes the evolution of multiple modalities of treatments, including multidisciplinary programs, multimodal therapy, interventional techniques, opioid therapy, other conservative modalities, and surgical interventions. This review emphasizes the individual, patient-centered development of an effective pain treatment plan after proper evaluation to establish a diagnosis. It includes measurable outcomes that focus on improvements in the quality of life and activities of daily living, as well as improvement in pain and function and, most importantly, return to productive citizenship. It is crucial that the knowledge of best practices be advanced, along with emphasis on lessons learned in the past to provide best practices for better pain management.

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