دورية أكاديمية
Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina II Neurons.
العنوان: | Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina II Neurons. |
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المؤلفون: | Zhang H; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China.; Department of Health Statistics, Fourth Military Medical University, Xi'an, 710032, China., Ma SB; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China., Gao YJ; Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key laboratory of Neuroregeneration, Nantong University, Nantong, 226001, China., Xing JL; Department of Radiation Biology, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, China., Xian H; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China.; Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China., Li ZZ; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China., Shen SN; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China.; Department of Stomatology, No. 984 Hospital of the People's Liberation Army, Beijing, 100094, China., Wu SX; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China., Luo C; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China. luoceng@fmmu.edu.cn., Xie RG; Department of Neurobiology, Fourth Military Medical University, Xi'an, 710032, China. rgxie@fmmu.edu.cn. |
المصدر: | Neuroscience bulletin [Neurosci Bull] 2020 Nov; Vol. 36 (11), pp. 1344-1354. Date of Electronic Publication: 2020 Aug 18. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 101256850 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-8218 (Electronic) Linking ISSN: 19958218 NLM ISO Abbreviation: Neurosci Bull Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Singapore : Springer Singapore Original Publication: Beijing, China : Science Press, 2005- |
مواضيع طبية MeSH: | N-Methylaspartate*/metabolism , Pain*, Chemokine CCL2/*metabolism , Extracellular Signal-Regulated MAP Kinases/*metabolism , Receptors, N-Methyl-D-Aspartate/*metabolism , Substantia Gelatinosa/*physiology, Animals ; Chemokine CCL2/antagonists & inhibitors ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; Signal Transduction |
مستخلص: | Previous studies have shown that CCL2 (C-C motif chemokine ligand 2) induces chronic pain, but the exact mechanisms are still unknown. Here, we established models to explore the potential mechanisms. Behavioral experiments revealed that an antagonist of extracellular signal-regulated kinase (ERK) inhibited not only CCL2-induced inflammatory pain, but also pain responses induced by complete Freund's adjuvant. We posed the question of the intracellular signaling cascade involved. Subsequent experiments showed that CCL2 up-regulated the expression of phosphorylated ERK (pERK) and N-methyl D-aspartate receptor [NMDAR] subtype 2B (GluN2B); meanwhile, antagonists of CCR2 and ERK effectively reversed these phenomena. Whole-cell patch-clamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway, which was blocked by antagonists of GluN2B and ERK. In summary, we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents, eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway. |
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فهرسة مساهمة: | Keywords: C-C motif chemokine ligand 2; Extracellular signal-regulated kinase; Monocyte chemoattractant protein 1; Neuron-glial interaction |
المشرفين على المادة: | 0 (Ccl2 protein, mouse) 0 (Chemokine CCL2) 0 (NR2B NMDA receptor) 0 (Receptors, N-Methyl-D-Aspartate) 6384-92-5 (N-Methylaspartate) EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) |
تواريخ الأحداث: | Date Created: 20200819 Date Completed: 20210728 Latest Revision: 20210728 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7674543 |
DOI: | 10.1007/s12264-020-00557-9 |
PMID: | 32809188 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1995-8218 |
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DOI: | 10.1007/s12264-020-00557-9 |