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The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.
Learn More >It is generally acknowledged that osteopathic physicians take a holistic approach to patient care. This style may help prevent the progression of painful musculoskeletal conditions, particularly if combined with osteopathic manipulative treatment (OMT).
Learn More >Opioid use for treatment of persistent pain has increased dramatically over the past two decades, but it has not resulted in improved pain management outcomes. To understand the molecular mechanisms of opioids, molecular signatures that arise from opioid exposure are often sought after, using various analytical methods. In this study, we performed proteomics, and multiglycomics via sequential analysis of polysialic acids, glycosaminoglycans, N-glycans and O-glycans, using the same cerebral spinal fluid (CSF) sample from patients that had long-term (>2 years), intrathecal morphine or baclofen administered via an indwelling pump. Proteomics and N-glycomics signatures between the two treatment groups were highly conserved, while significant differences were observed in polysialic acid, heparan sulfate glycosaminoglycan and O-glycan profiles between the two treatment groups. This represents the first study to investigate the potential relationships between diverse CSF conjugated glycans and long-term intrathecal drug exposure. The unique changes, observed by a sequential analytical workflow, reflect previously undescribed molecular effects of opioid administration and pain management.
Learn More >We aimed to adopt a multidimensional approach and investigate the interconnections between biomarkers (cytokines, matrix metalloproteinases, and cortisol) and psychosocial aspects considering pain acceptance, the individual construct of pain perception in terms of blood inflammation biomarkers, anxiety, self-efficacy, and functional performance and to define the quality of life (QoL) in women with rheumatoid arthritis (RA).
Learn More >The most common disabling symptom of osteoarthritis (OA) is pain. Clinical investigations using disease-specific animal models have increased our insights into the pathophysiology of osteoarthritic pain. As the prevalence of OA continues to rise and current available treatment options give less than optimal levels of pain relief, opportunities to develop treatments to address osteoarthritic pain are increasing. Targeted administration of local anesthetics along sensory/motor nerves can provide an alternative strategy for managing osteoarthritic pain. Moreover, the development of engineered therapeutic drug delivery systems may allow for sustained perineural delivery of local anesthetics as opposed to the traditional intraarticular joint injections. This review presents an overview of 1) the pathophysiology of persistent pain associated with OA of the hip, shoulder, and knee and 2) the emerging therapeutic role of local anesthetics in providing analgesia for joint-related pain symptoms.
Learn More >Substantial patient racial and ethnic differences in opioid prescribing have been documented, but how much of these differences were attributable to physicians prescribing opioids differently to patients of racial and ethnic minority groups is unknown, particularly during the first wave of the opioid epidemic when the dangers of opioid prescribing and use were not as well known.
Learn More >Atopic dermatitis (AD) is a chronic inflammatory skin disease with pruritus, characterized by recurrent eczema with exacerbations and remissions. AD impairs patients' QOL and places a heavy burden on patients. Recently, dupilumab, an anti-IL-4Rα antibody, was approved for the treatment of patients with moderate-to-severe AD who are refractory to topical agents and/or conventional systemic therapy. Clinical trials of dupilumab for AD demonstrated high efficacy and tolerable safety profiles. Furthermore, real-world evidence of dupilumab for AD is accumulating. Most of these data show favorable effectiveness and safety profile; however, they also clarified issues, including conjunctivitis and facial redness. There are still a certain number of patients with significant failure. In this article, we review real-world evidence of dupilumab for AD, identify concerns specific to dupilumab, and discuss unmet needs and issues to be addressed in the future.
Learn More >The older population is growing and with this growth there is a parallel rise in the operations performed on this vulnerable group. The perioperative pain management strategy for older adults is unique and requires a team-based approach for provision of high-quality surgical care.
Learn More >The high prevalence and societal burden of chronic pain, its undertreatment, and disparities in its management have contributed to the acknowledgment of chronic pain as a serious public-health concern. The concurrent opioid epidemic, and increasing concern about overreliance on opioid therapy despite evidence of limited benefit and serious harms, has heightened attention to this problem. The biopsychosocial model has emerged as the primary conceptual framework for understanding the complex experience of chronic pain and for informing models of care. The prominence of psychological processes as risk and resilience factors in this model has prompted extensive study of psychological treatments designed to alter processes that underlie or significantly contribute to pain, distress, or disability among adults with chronic pain. Cognitive-behavioral therapy is acknowledged to have strong evidence of effectiveness; other psychological approaches, including acceptance and commitment therapy, mindfulness, biofeedback, hypnosis, and emotional-awareness and expression therapy, have also garnered varying degrees of evidence across multiple pain conditions. Mechanistic studies have identified multiple pathways by which these treatments may reduce the intensity and impact of pain. Despite the growing evidence for and appreciation of these approaches, several barriers limit their uptake at the level of organizations, providers, and patients. Innovative methods for delivering psychological interventions and other research, practice, and policy initiatives hold promise for overcoming these barriers. Additional scientific knowledge and practice gaps remain to be addressed to optimize the reach and effectiveness of these interventions, including tailoring to address individual differences, concurrently addressing co-occurring disorders, and incorporating other optimization strategies.
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