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Effect of Intramuscular vs Intra-articular Glucocorticoid Injection on Pain Among Adults With Knee Osteoarthritis: The KIS Randomized Clinical Trial.

Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach.

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Amygdala functional connectivity mediates the association between catastrophizing and threat-safety learning in youth with chronic pain.

There is a need to identify brain connectivity alterations predictive of transdiagnostic processes that may confer vulnerability for affective symptomology. Here, we tested whether amygdala resting-state functional connectivity (rsFC) mediated the relationship between catastrophizing (negative threat appraisals and predicting poorer functioning) and altered threat-safety discrimination learning (critical to flexibly adapt to new and changing environments) in adolescents with persistent pain. We examined amygdala rsFC in 46 youth with chronic pain and 29 healthy peers (age M = 15.8, SD = 2.9; 64 females) and its relationship with catastrophizing and threat-safety learning. We used a developmentally appropriate threat-safety learning paradigm and performed amygdala seed-based rsFC and whole-brain mediation analyses. Patients exhibited enhanced connectivity between the left amygdala and right supramarginal gyrus (SMG) (cluster-level P-FDR < 0.05), whereas right amygdala rsFC showed no group differences. Only in patients, elevated catastrophizing was associated with facilitated threat-safety learning (CS+>CS-; rp = 0.49, P = 0.001). Furthermore, in patients, elevated catastrophizing was associated with reduced left amygdala connectivity with SMG / parietal operculum, and increased left amygdala connectivity with hippocampus, dorsal striatum, paracingulate, and motor regions (P < 0.001). In addition, blunted left amygdala rsFC with right SMG/parietal operculum mediated the association between catastrophizing and threat-safety learning (P < 0.001). To conclude, rsFC between the left amygdala (a core emotion hub) and inferior parietal lobe (involved in appraisal and integration of bodily signals and attentional reorienting) explains associations between daily-life relevant catastrophizing and threat-safety learning. Findings provide a putative model for understanding pathophysiology involved in core psychological processes that cut across diagnoses, including disabling pain, and are relevant for their etiology.

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Revisiting the impact of race/ethnicity in endometriosis.

Endometriosis is a chronic, multisystemic disease often presenting with significant phenotypic variation amongst patients. The impact of race/ethnicity on the prevalence of endometriosis, as well as disease presentation, is a question of interest which has been explored for the last century. This narrative review explores the historical perspective of endometriosis and race/ethnicity as well as the evidence available to date. Furthermore, we discuss the potential implication of the bias perpetuated on this topic, specifically in the areas of medical education, research, and clinical care. In consideration of these intersecting realms, we suggest priorities for future consideration of race/ethnicity as it pertains to the delivery of care for endometriosis patients.

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Identifying functional brain abnormalities in migraine and depression comorbidity.

Migraine and major depressive disorder (MDD) are both highly prevalent brain disorders and are often comorbid. However, the common and distinctive neural mechanisms underlying these disorders and the brain function alterations associated with their comorbidity are largely unknown. We aimed to explore the functional abnormalities of the brain associated with the co-occurrence of migraine and depression.

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A prospective long-term follow-up of dorsal root ganglion stimulation for the management of chronic intractable pain.

Initial clinical studies have shown that the stimulation of the dorsal root ganglion (DRG) can significantly reduce chronic intractable pain. However, clinical data on long-term results and complications of these systems are limited. The aim of this prospective study is to report on a single center long-term follow-up of DRG stimulation for intractable chronic pain. Participants were implanted with DRG stimulation devices between 2013 and 2015 with an observation period of 24 months. Patients were contacted again in 2020 for a final follow-up (ie, between 5 and 7 years postimplantation). Forty-two participants were recruited, of whom 32 received the fully implantable pulse generator (IPG). At the final follow-up, 50% (16/32) of participants were still using DRG stimulation. Two participants still had the original IPG and 14 had received a replacement IPG. Pain scores were significantly reduced at 24 months, mean difference 1.7 (95% confidence interval: 0.2-3.3, P = 0.03), and at the last follow-up, mean difference 2.1 (95% confidence interval: 0.3-4, P = 0.03). Significant improvements were observed for health-related quality of life. The findings were generally robust to imputation methods of missing data. Implantable pulse generators of 8 patients were explanted because of dissatisfaction with pain relief. In conclusion, DRG stimulation can provide effective pain relief and improved quality of life in patients suffering with neuropathic pain, although this study had a revision rate of 42% within the first 24 months, and 56% of IPGs that were replaced because of battery depletion had a shorter than expected battery life.

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Postoperative Multimodal Pain Management and Opioid Consumption in Arthroscopy Clinical Trials: A Systematic Review.

To provide an updated review of multimodal pain management in arthroscopic surgery by evaluating pain and opioid consumption after shoulder, knee, and hip arthroscopy.

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Calcitonin gene-related peptide is not involved in neuropathic pain induced by partial sciatic nerve ligation in mice.

Optimal neuropathic pain (NeP) therapy has still not been established despite great efforts to develop new strategies for NeP analgesia. One possible target might be calcitonin gene-related peptide (CGRP). This is because the expression of CGRP and its receptors in the dorsal horn of the spinal cord might be associated with the persistence of pain symptoms including symptoms of NeP. We previously developed αCGRP knockout mice, and we aimed in this study to clarify the roles of CGRP in NeP by partial sciatic nerve ligation (PSNL) using the knockout mice.

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Chronic Postoperative Pain and Microorganisms: The Good, the Bad, and the Ugly.

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Association of Opioid Dose Reduction With Opioid Overdose and Opioid Use Disorder Among Patients Receiving High-Dose, Long-term Opioid Therapy in North Carolina.

Rapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction but are based on limited evidence.

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Exploring nose to brain nano delivery for effective management of migraine.

Migraine is a disabling disease, characterized by severe throbbing headache. Patients demand quick relief from this pain. The presence of blood brain barrier does not permit the drug to penetrate the brain effectively. Administration of conventional anti-migraine medications via oral route leads to erratic absorption of drugs. Delayed gastric emptying is also responsible for ineffective absorption of drug. Migraine induced nausea and vomiting, further limits patient compliance to oral medication. Other limitations associated with oral route include extensive first pass metabolism, slow onset of action, inability to cross blood brain barrier and requirement of large amount of dose/dosage and frequent administration. The anti-migraine drugs used in migraine like triptans are therapeutically effective but have low bioavaialability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs oral tritpans, Ergot amine, NSAIDs and CGRP antagonist is quite high because of their poor bioavailability. As a result of these drugs are associated with several side effects. This aspects necessitates the need of developing a dosage form that can deliver drug directly brain thereby reducing the dose. Use of invasive techniques to deliver these therapeutics to the brain do exist, however, they are painful, require expert assistance and are not cost-effective approach for migraine treatment. These limitations demand development of a novel non-invasive approach that is safe, efficacious and has high patient compliance. As, reported it is possible to target the brain tissue by administering the drug intranasally using olfactory and the trigeminal pathway. This route is non-invasive, avoids first-pass metabolism, eliminates nausea and vomiting, helps reduce dose, and thus helps achieve increase patient compliance. Some factors like solubility, lipophilicity of the drug, mucociliary clearance, enzymatic degradation hinder the bioavailability of the drug by nasal route. Therefore, there is a grave need to develop novel nasal formulations with prolonged nasal residence time, which can modulate pharmacokinetics for adequate therapeutic response, and render efficient yet robust brain targeting. It is necessary to consider these challenges in developing efficient intranasal dosage form. This review gives a brief overview of all the novel carriers reported for improving the treatment of migraine. Nanocarrier based delivery systems like in-situ gels, micro emulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.

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