دورية أكاديمية
Astrocyte PERK and IRE1 Signaling Contributes to Morphine Tolerance and Hyperalgesia through Upregulation of Lipocalin-2 and NLRP3 Inflammasome in the Rodent Spinal Cord.
| العنوان: | Astrocyte PERK and IRE1 Signaling Contributes to Morphine Tolerance and Hyperalgesia through Upregulation of Lipocalin-2 and NLRP3 Inflammasome in the Rodent Spinal Cord. |
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| المؤلفون: | Wang B; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Jiangsu, China; Department of Pain Management, First Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China; and Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey (current position)., Wang LN; Department of Pain Management, First Affiliated Hospital of Soochow University, Suzhou, China., Wu B; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Jiangsu, China., Guo R; Department of Pain, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China., Zhang L; Department of Anesthesiology, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Kunshan, Jiangsu Province, China., Zhang JT; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Jiangsu, China., Wang ZH; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China., Wu F; Department of Pain Management, First Affiliated Hospital of Soochow University, Suzhou, China., Feng Y; Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China., Liu H; Department of Pain Management, First Affiliated Hospital of Soochow University, Suzhou, China., Jin XH; Department of Pain Management, First Affiliated Hospital of Soochow University, Suzhou, China., Miao XH; Department of Pain, The Affiliated Hospital of Nantong University, Nantong, China., Liu T; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Jiangsu, China; and College of Life Sciences, Yanan University, Yanan, China. |
| المصدر: | Anesthesiology [Anesthesiology] 2024 Mar 01; Vol. 140 (3), pp. 558-577. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 1300217 Publication Model: Print Cited Medium: Internet ISSN: 1528-1175 (Electronic) Linking ISSN: 00033022 NLM ISO Abbreviation: Anesthesiology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Philadelphia Pa : Lippincott Williams & Wilkins Original Publication: Philadelphia : American Society of Anesthesiologists |
| مواضيع طبية MeSH: | Morphine*/pharmacology , Inflammasomes*/metabolism, Rats ; Mice ; Male ; Female ; Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Astrocytes/metabolism ; Hyperalgesia/metabolism ; Rodentia/metabolism ; Up-Regulation ; Lipocalin-2/metabolism ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Spinal Cord/metabolism ; Cell Cycle Proteins/metabolism |
| مستخلص: | Background: Endoplasmic reticulum stress plays a crucial role in the pathogenesis of neuroinflammation and chronic pain. This study hypothesized that PRKR-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme type 1 (IRE1) regulate lipocalin-2 (LCN2) and Nod-like receptor family pyrin domain containing 3 (NLRP3) expression in astrocytes, thereby contributing to morphine tolerance and hyperalgesia. Methods: The study was performed in Sprague-Dawley rats and C57/Bl6 mice of both sexes. The expression of LCN2 and NLRP3 was assessed by Western blotting. The tail-flick, von Frey, and Hargreaves tests were used to evaluate nociceptive behaviors. Chromatin immunoprecipitation was conducted to analyze the binding of activating transcription factor 4 (ATF4) to the promoters of LCN2 and TXNIP. Whole-cell patch-clamp recordings were used to evaluate neuronal excitability. Results: Pharmacologic inhibition of PERK and IRE1 attenuated the development of morphine tolerance and hyperalgesia in male (tail latency on day 7, 8.0 ± 1.13 s in the morphine + GSK2656157 [10 μg] group vs. 5.8 ± 0.65 s in the morphine group; P = 0.04; n = 6 rats/group) and female (tail latency on day 7, 6.0 ± 0.84 s in the morphine + GSK2656157 [10 μg] group vs. 3.1 ± 1.09 s in the morphine group; P = 0.0005; n = 6 rats/group) rats. Activation of PERK and IRE1 upregulated expression of LCN2 and NLRP3 in vivo and in vitro. Chromatin immunoprecipitation analysis showed that ATF4 directly bound to the promoters of the LCN2 and TXNIP. Lipocalin-2 induced neuronal hyperexcitability in the spinal cord and dorsal root ganglia via melanocortin-4 receptor. Conclusions: Astrocyte endoplasmic reticulum stress sensors PERK and IRE1 facilitated morphine tolerance and hyperalgesia through upregulation of LCN2 and NLRP3 in the spinal cord. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.) |
| المشرفين على المادة: | 76I7G6D29C (Morphine) 0 (Inflammasomes) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Lipocalin-2) EC 2.7.11.1 (Protein Serine-Threonine Kinases) 0 (TXNIP protein, rat) 0 (Cell Cycle Proteins) |
| تواريخ الأحداث: | Date Created: 20231211 Date Completed: 20240214 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| DOI: | 10.1097/ALN.0000000000004858 |
| PMID: | 38079113 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1528-1175 |
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| DOI: | 10.1097/ALN.0000000000004858 |