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Effects of selective inhibition of prostaglandin E2 receptors EP2 and EP4 on the miRNA profile in endometriosis.

Endometriosis is an estrogen-dependent, progesterone-resistant, chronic inflammatory gynecological disease of reproductive-age women. Two major clinical symptoms of endometriosis are chronic pelvic pain and infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent disease recurrence. Prostaglandin E (PGE) plays an important role in the survival and growth of endometriotic lesions. MicroRNAs (miRNAs) are small, noncoding RNAs that control gene expressions through multiple mechanisms and have important roles in the pathogenesis of endometriosis. The objective of the present study is to determine the effects of pharmacological inhibition of PGE receptors, EP2 and EP4, on miRNA profile in endometriosis. The novel results collectively indicate that inhibition of PGE-EP2/EP4 signaling regulated several miRNA clusters associated with cell adhesion, migration, invasion, survival and growth in cell-specific and the chromosome-specific manner and reverses the epigenetic silencing of proapoptotic miRNAs 15a and 34c in the human endometriotic epithelial and stromal cells and experimental endometriotic lesions. Thus, selective inhibition of EP2/EP4 receptors could emerge as a potential nonsteroidal therapy for endometriosis.

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Response to “Choroidal thickness in eyes of migraine patients measured using spectral domain-optical coherence tomography: A meta-analysis”.

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Mindfulness-Based Interdisciplinary Pain Management Program for Complex Polymorbid Pain in Veterans: A Randomized Clinical Trial.

To evaluate the effects of interdisciplinary pain management on pain-related disability and opioid reduction in polymorbid pain patients with two or more comorbid psychiatric conditions.

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Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study.

Patients often report various symptoms after recovery from acute COVID-19. Previous studies on post-COVID-19 condition have not corrected for the prevalence and severity of these common symptoms before COVID-19 and in populations without SARS-CoV-2 infection. We aimed to analyse the nature, prevalence, and severity of long-term symptoms related to COVID-19, while correcting for symptoms present before SARS-CoV-2 infection and controlling for the symptom dynamics in the population without infection.

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What is the purpose of the diagnostic criterion for fibromyalgia?

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An experimental study to inform adoption of mindfulness-based stress reduction in chronic low back pain.

Chronic low back pain is a common and sometimes disabling condition, and mindfulness-based stress reduction is recommended as a first line of therapy. This study tested whether different descriptions of mindfulness training altered based on influential intervention characteristics increased adoption intentions.

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An International Multidisciplinary Delphi-Based Consensus on Heat Therapy in Musculoskeletal Pain.

Musculoskeletal pain (MP) is prevalent in our society, having a strong negative impact on physical and psychosocial quality of life. Heat therapy (HT) has been frequently described as a treatment strategy for musculoskeletal pain, but scientific evidence is still poor. The aim of the present Delphi method study is to gather a consensus among European experts on the role of HT in MP.

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Empowering Physical Therapist Professional Education Programs to Deliver Modern Pain Content.

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Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain.

Trigeminal neuralgia, historically dubbed the "suicide disease," is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)-approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery. Here, we identify the NRF2 transcriptional network as a potential therapeutic target. We report that cerebrospinal fluid from patients with trigeminal neuralgia accumulates reactive oxygen species, several of which directly activate the pain-transducing channel TRPA1. Similar to our patient cohort, a mouse model of trigeminal neuropathic pain also exhibits notable oxidative stress. We discover that stimulating the NRF2 antioxidant transcriptional network is as analgesic as inhibiting TRPA1, in part by reversing the underlying oxidative stress. Using a transcriptome-guided drug discovery strategy, we identify two NRF2 network modulators as potential treatments. One of these candidates, exemestane, is already FDA-approved and may thus be a promising alternative treatment for trigeminal neuropathic pain.

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Unravelling the role of unmyelinated nerve fibres in trigeminal neuralgia with concomitant continuous pain.

In this clinical and neurophysiological study, we aimed to test trigeminal nerve fibre function in patients with trigeminal neuralgia, with and without concomitant continuous pain.

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