Articles: function.
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Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p-induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. ⋯ Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain.
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Anesthesia and analgesia · Jul 2023
Practice Advisory for Preoperative and Intraoperative Pain Management of Cardiac Surgical Patients: Part 2.
Pain after cardiac surgery is of moderate to severe intensity, which increases postoperative distress and health care costs, and affects functional recovery. Opioids have been central agents in treating pain after cardiac surgery for decades. The use of multimodal analgesic strategies can promote effective postoperative pain control and help mitigate opioid exposure. ⋯ This Practice Advisory provides recommendations for providers caring for patients undergoing cardiac surgery. This entails developing customized pain management strategies for patients, including preoperative patient evaluation, pain management, and opioid use-focused education as well as perioperative use of multimodal analgesics and regional techniques for various cardiac surgical procedures. The literature related to this field is emerging, and future studies will provide additional guidance on ways to improve clinically meaningful patient outcomes.
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Most hospitalized children experience pain that is often inadequately assessed and undertreated. Exposure to undertreated childhood pain is associated with negative short-term and long-term outcomes and can detrimentally affect families, health services, and communities. Adopting electronic medical records (EMRs) in pediatric hospitals is a promising mechanism to transform care. ⋯ A qualitative descriptive study design was used and 14 nursing and medical experts from 5 countries (United States, Canada, United Kingdom, Australia, and Qatar) were interviewed online using Zoom for Healthcare. We applied a reflexive content analysis to the data and constructed 4 broad categories: "capturing the pain story," "working with user-friendly systems," "patient and family engagement and shared decision making," and "augmenting pain knowledge and awareness." These findings outline expert recommendations for EMR designs that facilitate broad biopsychosocial pain assessments and multimodal treatments, and customized functionality that safeguards high-risk practices without overwhelming clinicians. Future research should study the use of patient-controlled and family-controlled interactive bedside technology to and their potential to promote shared decision making and optimize pain care outcomes.
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Targeting the vascular endothelial growth factor A/neuropilin 1 axis for relief of neuropathic pain.
Vascular endothelial growth factor A (VEGF-A) is a pronociceptive factor that causes neuronal sensitization and pain. We reported that blocking the interaction between the membrane receptor neuropilin 1 (NRP1) and VEGF-A-blocked VEGF-A-mediated sensory neuron hyperexcitability and reduced mechanical hypersensitivity in a rodent chronic neuropathic pain model. These findings identified the NRP1-VEGF-A signaling axis for therapeutic targeting of chronic pain. ⋯ In rats with spared nerve injury-induced neuropathic pain, intrathecal administration of NRP1-4 significantly attenuated mechanical allodynia. Intravenous treatment with NRP1-4 reversed both mechanical allodynia and thermal hyperalgesia in rats with L5/L6 spinal nerve ligation-induced neuropathic pain. Collectively, our findings show that NRP1-4 is a first-in-class compound targeting the NRP1-VEGF-A signaling axis to control voltage-gated ion channel function, neuronal excitability, and synaptic activity that curb chronic pain.
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Acta Anaesthesiol Scand · Jul 2023
Regional wall motion abnormalities in critically ill patients with non-obstructed coronary arteries.
Left ventricular (LV) dysfunction is estimated to occur in 10%-25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population. ⋯ RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.