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Transcutaneous auricular vagus nerve stimulation at 1 Hz modulates locus coeruleus activity and resting state functional connectivity in patients with migraine: An fMRI study.

Migraine is a common episodic neurological disorder. Literature has shown that transcutaneous auricular vagus nerve stimulation (taVNS) at 1 Hz can significantly relieve migraine symptoms. However, its underlying mechanism remains unclear. This study aims to investigate the neural pathways associated with taVNS treatment of migraine.

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Neuroimaging Studies of Antidepressant Placebo Effects: Challenges and Opportunities.

Over the last two decades, neuroscientists have used antidepressant placebo probes to examine the biological mechanisms implicated in expectancies of mood improvement.However, findings from these studies have yet to elucidate a model-based theory that would explain the mechanisms through which antidepressant expectancies evolve to induce persistent mood changes. Compared to other fields, the development of experimental models of antidepressant placebo effects faces significant challenges, such as the delayed mechanism of action of conventional antidepressants and the complex internal dynamics of mood. Still, recent neuroimaging studies of antidepressant placebo effects have shown remarkable similarities to those observed in other disciplines (e.g., placebo analgesia), such as placebo-induced increased µ-opioid signaling and blood-oxygen-level dependent (BOLD) responses in areas involved in cognitive control, the representation of expected values and reward and emotional processing. This review will summarize these findings and the challenges and opportunities that arise from applying methodologies used in the field of placebo analgesia into the field of antidepressant placebo effects.

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Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine: Evidence From Randomized Controlled Trials.

As one of the novel therapeutic drugs that targets Calcitonin gene-related peptide (CGRP), 75 mg rimegepant has been used for the acute management of migraine, which is one of the most common neurological diseases worldwide. Several clinical trials have been conducted to investigate the efficacy and safety of rimegepant for the acute management of migraine, but no systematic review of existing literature has been performed. We therefore performed a meta-analysis to investigate the efficacy and safety of rimegepant in treatment of patients with migraine.

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Developing Modern Pain Therapies.

Chronic pain afflicts as much as 50% of the population at any given time but our methods to address pain remain limited, ineffective and addictive. In order to develop new therapies an understanding of the mechanisms of painful sensitization is essential. We discuss here recent progress in the understanding of mechanisms underlying pain, and how these mechanisms are being targeted to produce modern, specific therapies for pain. Finally, we make recommendations for the next generation of targeted, effective, and safe pain therapies.

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Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain.

A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? To clarify this question, 19 chronic pain subjects and 19 age- and gender-matched control subjects without pain underwent magnetic resonance spectroscopy. Both groups also completed the Temperament and Character, the Beck Depression and the State Anxiety Inventories to measure levels of harm avoidance, depression, and anxiety, respectively. People with chronic pain had significantly higher scores in harm avoidance, depression and anxiety compared to control subjects without pain. High levels of harm avoidance are characterized by excessive worry, pessimism, fear, doubt and fatigue. Individuals with chronic pain showed a significant decrease in mPFC glutamate levels compared to control subjects without pain. In people with chronic pain mPFC glutamate levels were significantly negatively correlated with harm avoidance scores. This means that the lower the concentration of glutamate in the mPFC, the greater the total scores of harm avoidance. High scores are associated with fearfulness, pessimism, and fatigue-proneness. We suggest that chronic pain, particularly the stress-induced release of glucocorticoids, induces changes in glutamate transmission in the mPFC, thereby influencing cognitive, and emotional processing. Thus, in people with chronic pain, regulation of fear, worry, negative thinking and fatigue is impaired.

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US national trends in pediatric deaths from prescription and illicit opioids, 1999-2016.

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Trends in opioid use in pediatric patients in US emergency departments from 2006 to 2015.

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Sex-dependent differences in pain and sleep in a porcine model of Neurofibromatosis type 1.

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Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.

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The sensory coding of warm perception.

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