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Journal article
Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function
The journal of pharmacology and experimental therapeutics, v 392(4), 103398
05 Feb 2025
PMID: 40054390
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
Morphine and other synthetic opioids are widely prescribed to treat pain. Prolonged morphine exposure can paradoxically enhance pain sensitivity in humans and nociceptive behavior in rodents. To better understand the molecular mechanisms underlying opioid-induced hyperalgesia, we investigated changes in miRNA composition of small extracellular vesicles (sEVs) from the serum of mice after a morphine treatment paradigm that induces hyperalgesia. We observed significant differential expression of 18 miRNAs in sEVs from morphine-treated mice of both sexes compared to controls. Several of these miRNAs were bioinformatically predicted to regulate cyclic AMP response element binding protein (CREB), a well-characterized transcription factor implicated in pain and drug addiction. We confirmed the binding and repression of Creb mRNA by miR-155 and miR-10a. We tested if serum-derived sEVs from morphine-treated mice could elicit nociceptive behavior in naïve recipient mice. Intrathecal injection of 1 μg sEVs did not significantly impact basal mechanical and thermal threshold in naïve recipient mice. However, prophylactic 1 μg sEV administration in recipient mice resulted in faster resolution of complete Freund’s adjuvant-induced mechanical and thermal inflammatory hypersensitivity. Other behaviors assayed following administration of these sEVs were not impacted including sEV conditioned place preference and locomotor sensitization. These results indicate that morphine regulation of serum sEV composition can contribute to analgesia and suggest a potential for sEVs to be a non-opioid therapeutic intervention strategy to treat pain.
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Details
- Title
- Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function
- Creators
- Seena Ajit (Corresponding Author) - Drexel University, Pharmacology and PhysiologyDeepa Reddy - Drexel UniversityZhucheng Lin - Drexel UniversitySujay Ramanathan - Drexel UniversityXuan Luo - Drexel UniversityRicha Pande - Drexel University, Pharmacology and PhysiologyYuzhen Tian - Drexel University, Pharmacology and PhysiologyChristine Marie Side - Drexel University, Pharmacology and PhysiologyJacqueline M Barker - Drexel University, Pharmacology and PhysiologyAhmet Sacan - Drexel University, School of Biomedical Engineering, Science, and Health SystemsJulie A Blendy - California University of Pennsylvania
- Publication Details
- The journal of pharmacology and experimental therapeutics, v 392(4), 103398
- Publisher
- Elsevier
- Number of pages
- 14
- Grant note
- National Institutes of Health National Institute of Neurological Disorders and Stroke: R01 NS102836, R01NS129191, 1RF1NS130481 National Institutes of Health National Institute on Alcohol Abuse and Alcoholism: R21 AA030823 Drexel University College of Medicine
This study was partially supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants R01 NS102836, R01NS129191, and 1RF1NS130481] (to S.K.A.) and the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant R21 AA030823] (to J.M.B.) . D.R., X.L., and R.P. received Dean's Fellowship for Excellence in Collaborative or Themed Research from Drexel University College of Medicine.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001442019500001
- Scopus ID
- 2-s2.0-85219540076
- Other Identifier
- 991022024438304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy