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C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.
CNS Neurosci Ther
January 2025
Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Aims: Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.
View Article and Find Full Text PDFDRopEridol for Abdominal pain in the emergency department for Morphine Equivalent Reduction. The DREAMER study.
Am J Emerg Med
January 2025
Pharmacy Department, Wesley Medical Center, 550 N Hillside St, Wichita, KS 67214, United States of America.
Introduction: Droperidol is a dopamine-2 receptor antagonist in the class of butyrophenone antipsychotics with antiemetic, sedative, analgesic, and anxiolytic properties. In the postoperative setting, droperidol provides an opioid sparing effect and decreases nausea/vomiting. Another butyrophenone antipsychotic, haloperidol, has been shown to reduce morphine milliequivalents (MME) administered when used for abdominal pain in the emergency department (ED).
View Article and Find Full Text PDFCorticosteroid receptor antagonism in the medial prefrontal cortex reduces morphine-induced place preference and dopamine transporter expression decline in rats.
Neuroscience
January 2025
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address:
Corticosteroid signaling plays a critical role in modulating the neural systems underlying reward and addiction, but the specific contributions of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the medial prefrontal cortex (mPFC) to opioid reward and dopaminergic plasticity remain unclear. Here, we investigated the effects of intra-mPFC injection of corticosteroid receptor ligand (corticosterone; CORT), glucocorticoid receptor antagonist (RU38486; RU), and mineralocorticoid receptor antagonist (spironolactone; SP) on morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) expression in the mPFC. Adult male Wistar rats received intra-mPFC injections of CORT, RU, SP, or their respective vehicles prior to morphine CPP conditioning.
View Article and Find Full Text PDFEfficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction.
Proc Natl Acad Sci U S A
January 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.
View Article and Find Full Text PDFDo P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution?
J Pharmacokinet Pharmacodyn
January 2025
Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, Leiden, 2333 CC, The Netherlands.
P-glycoprotein (P-gp) is a key efflux transporter and may be involved in drug-drug interactions (DDIs) at the blood-brain barrier (BBB), which could lead to changes in central nervous system (CNS) drug exposure. Morphine is a P-gp substrate and therefore a potential victim drug for P-gp mediated DDIs. It is however unclear if P-gp inhibitors can induce clinically relevant changes in morphine CNS exposure.
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