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Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization.

The amyloid precursor protein (APP) is critical for the pathogenesis of Alzheimer's disease (AD). The AD patients usually have lower pain sensitivity in addition to cognitive impairments. However, considerably less is known as yet about the role of APP and its two mammalian homologues, amyloid precursor-like protein 1 and 2 (APLP1, APLP2), in spinal processing of nociceptive information. Here we found that all APP family members were present in spinal cord dorsal horn of adult male C57BL/6J mice. Peripheral nerve injury specifically reduced the expression of spinal APLP2 that correlated with neuropathic mechanical allodynia. The loss of APLP2 was confined to inhibitory GABAergic interneurons. Targeted knockdown of APLP2 in GABAergic interneurons of GAD2-Cre mice evoked pain hypersensitivity by means of microglia activation. Our data showed that GABAergic terminals expressed APLP2, a putative cell adhesion protein that interacted with microglia-specific integrin molecule CD11b. Knocking down APLP2 in GAD2-positive neurons to disrupt the trans-cellular interaction led to microglia-dependent pain sensitization. Our data thus revealed an important role of APLP2 for GABAergic interneurons to control microglial activity and pain sensitivity.

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Midterm Outcomes of Endoscopic Plantar Fascia Debridement in 125 Patients: A 5-Year Follow-Up.

Plantar fasciitis is one of the most common pathologies addressed by foot and ankle surgeons. Despite advances and overall success rates for conservative therapy, many of the recalcitrant cases proceed to require surgical correction. Partial to complete release of the fascia is often performed altering foot biomechanics and severing the windlass mechanism. Endoscopic debridement of the plantar fascia allows for direct visualization and removal of the inflammatory tissue while leaving the fascia and its function intact. A total of 125 feet were evaluated with a minimum follow-up time of 5 years. Gender, body mass index, and duration of symptoms were all evaluated and documented. Visual analog scale scores (VAS), American Orthopedic Foot and Ankle Score (AOFAS), and Foot Function Index (FFI) were collected both pre- and postoperatively. AOFAS, FFI, and VAS scores improved from a pre-operative mean of 57.6, 89.4%, and 8.6-89.1, 13.4%, and 0.7 respectively (p < .05) at final follow-up. Of the 125 patients, 98% stated they were satisfied with the operative outcome and would undergo the procedure again. At final follow-up, no patient suffered rupture of the fascia or recurrence. Patients were able to bear weight immediately following the surgery in a walking boot and on average patients were able to return to work at 3.4 days following surgery. This is a novel technique that does not compromise the plantar fascia or alter foot biomechanics with promising 5-year outcomes.

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Factors That Affect Opioid Quality Improvement Initiatives in Primary Care: Insights from Ten Health Systems.

To improve patient safety and pain management, the Centers for Disease Control and Prevention (CDC) released the Guideline for Prescribing Opioids for Chronic Pain (CDC Guideline). Recognizing that issuing a guideline alone is insufficient for transforming practice, CDC supported an Opioid Quality Improvement (QI) Collaborative, consisting of 10 health care systems that represented more than 120 practices across the United States. The research team identified factors related to implementation success using domains described by the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) implementation science framework.

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Treatment of Persistent or Recurrent Varicoceles: A Systematic Review.

The outcomes and morbidity following treatment for persistent or varicocele recurrence remain controversial.

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Diagnosing new daily persistent headache in children and adolescents: A survey of clinicians.

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Alcohol as a trigger of migraine attacks in people with migraine. Results from a large prospective cohort study in English-speaking countries.

To assess whether alcohol intake is associated with the onset of migraine attacks up to 2 days after consumption in individuals with episodic migraine (EM).

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Instagram, risky drinking and main health effects in Spanish adolescents in the COVID-19 pandemic. A qualitative study.

The aim of this study was to analyze the relationship between Instagram, alcohol consumption and the impact on adolescent health during the COVID-19 pandemic.

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The efficacy of oral corticosteroids for treatment of Tietze syndrome: A pragmatic randomized controlled trial.

Tietze syndrome is a rare form of chest wall costochondritis with joint swelling which can cause significant chest pain and decline in ability of daily activities. There is no standardized treatment protocol. The aim of this study was to assess the efficacy of adding oral steroids in addition to other non- steroidal treatment in improvement of pain and quality of life (QOL) in patients with Tietze syndrome.

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A neural circuit for the suppression of feeding under persistent pain.

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, we show that a circuit arising from glutamatergic neurons in the anterior cingulate cortex (Glu) projects to glutamatergic neurons in the lateral hypothalamic area (Glu) to blunt food intake in a mouse model of persistent pain. In turn, these Glu neurons project to pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus (POMC), a well-known neuronal population involved in decreasing food intake. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that the Glu → Glu → Arc circuit is activated in mouse models of persistent pain and is accompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the Glu → Glu → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway could be explored as a potential target for pain-associated diseases.

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Risk of cardiovascular events according to the tricyclic antidepressant dosage in patients with chronic pain: a retrospective cohort study.

We aimed to examine the risk of cardiovascular adverse events by tricyclic antidepressant (TCA) dosage among patients with chronic pain.

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