دورية أكاديمية
أعرض في EDS

Combined use of CLP290 and bumetanide alleviates neuropathic pain and its mechanism after spinal cord injury in rats.

التفاصيل البيبلوغرافية
العنوان: Combined use of CLP290 and bumetanide alleviates neuropathic pain and its mechanism after spinal cord injury in rats.
المؤلفون: Pan YZ; Rehabilitation Medicine Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, China., Talifu Z; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, China.; Chinese Institute of Rehabilitation Science, Beijing, China., Wang XX; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Chinese Institute of Rehabilitation Science, Beijing, China., Ke H; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Chinese Institute of Rehabilitation Science, Beijing, China., Zhang CJ; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Chinese Institute of Rehabilitation Science, Beijing, China., Xu X; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Chinese Institute of Rehabilitation Science, Beijing, China., Yang DG; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China., Yu Y; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Chinese Institute of Rehabilitation Science, Beijing, China.; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China., Du LJ; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China., Gao F; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.; Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China., Li JJ; School of Rehabilitation Medicine, Capital Medical University, Beijing, China.; Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.; Chinese Institute of Rehabilitation Science, Beijing, China.; Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.
المصدر: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2024 Sep; Vol. 30 (9), pp. e70045.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, UK : Wiley-Blackwell, c2008-
مواضيع طبية MeSH: Bumetanide*/pharmacology , Bumetanide*/therapeutic use , Spinal Cord Injuries*/complications , Spinal Cord Injuries*/drug therapy , Spinal Cord Injuries*/metabolism , Neuralgia*/drug therapy , Neuralgia*/etiology , Neuralgia*/metabolism , Rats, Sprague-Dawley* , Symporters*/metabolism , K Cl- Cotransporters* , Solute Carrier Family 12, Member 2*/metabolism, Animals ; Rats ; Male ; Sodium Potassium Chloride Symporter Inhibitors/pharmacology ; Sodium Potassium Chloride Symporter Inhibitors/therapeutic use ; Drug Therapy, Combination ; Spinal Cord/drug effects ; Spinal Cord/metabolism ; Hyperalgesia/drug therapy ; Hyperalgesia/etiology ; Acetates ; Indenes
مستخلص: Aim: We aimed to explore whether the combination of CLP290 and bumetanide maximally improves neuropathic pain following spinal cord injury (SCI) and its possible molecular mechanism.
Methods: Rats were randomly divided into five groups: Sham, SCI + vehicle, SCI + CLP290, SCI + bumetanide, and SCI + combination (CLP290 + bumetanide). Drug administration commenced on the 7th day post-injury (7 dpi) and continued for 14 days. All rats underwent behavioral assessments for 56 days to comprehensively evaluate the effects of interventions on mechanical pain, thermal pain, cold pain, motor function, and other relevant parameters. Electrophysiological assessments, immunoblotting, and immunofluorescence detection were performed at different timepoints post-injury, with a specific focus on the expression and changes of KCC2 and NKCC1 proteins in the lumbar enlargement of the spinal cord.
Results: CLP290 and bumetanide alleviated SCI-associated hypersensitivity and locomotor function, with the combination providing enhanced recovery. The combined treatment group exhibited the most significant improvement in restoring Rate-Dependent Depression (RDD) levels. In the combined treatment group and the two individual drug administration groups, the upregulation of potassium chloride cotransporter 2 (K + -Cl - cotransporter 2, KCC2) expression and downregulation of sodium potassium chloride cotransporter 1 (Na + -K + -Cl - cotransporter 1, NKCC1) expression in the lumbar enlargement area resulted in a significant increase in the KCC2/NKCC1 ratio compared to the SCI + vehicle group, with the most pronounced improvement seen in the combined treatment group. Compared to the SCI + vehicle group, the SCI + bumetanide group showed no significant paw withdrawal thermal latency (PWTL) improvement at 21 and 35 dpi, but a notable enhancement at 56 dpi. In contrast, the SCI + CLP290 group significantly improved PWTL at 21 days, with non-significant changes at 35 and 56 days. At 21 dpi, KCC2 expression was marginally higher in monotherapy groups versus SCI + vehicle, but not significantly. At 56 dpi, only the SCI + bumetanide group showed a significant difference in KCC2 expression compared to the control group.
Conclusion: Combined application of CLP290 and bumetanide effectively increases the ratio of KCC2/NKCC1, restores RDD levels, enhances GABA A receptor-mediated inhibitory function in the spinal cord, and relieves neuropathic pain in SCI; Bumetanide significantly improves neuropathic pain in the long term, whereas CLP290 demonstrates a notable short-term effect.
(© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
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معلومات مُعتمدة: 2020kfdx 004 Special Fund for Joint Training of Doctoral Students between University of Health and Rehabilitation Sciences and China Rehabilitation Research Center; 2022ZX-18 Fund of General Project in China Rehabilitation Research Center; 2021CZ-2 Basic Scientific Research of the Central Public Welfare Research Institutes in China; 2019HZ-13 Sub-project of Beijing Science and Technology Plan
فهرسة مساهمة: Keywords: CLP290; KCC2; NKCC1; bumetanide; neuropathic pain; spinal cord injury
المشرفين على المادة: 0Y2S3XUQ5H (Bumetanide)
0 (Symporters)
0 (K Cl- Cotransporters)
0 (Solute Carrier Family 12, Member 2)
106105-17-3 (((2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy)acetic acid)
0 (Slc12a2 protein, rat)
0 (Sodium Potassium Chloride Symporter Inhibitors)
0 (Acetates)
0 (Indenes)
تواريخ الأحداث: Date Created: 20240913 Date Completed: 20240913 Latest Revision: 20240917
رمز التحديث: 20240917
مُعرف محوري في PubMed: PMC11393004
DOI: 10.1111/cns.70045
PMID: 39267289
قاعدة البيانات: MEDLINE
الوصف
تدمد:1755-5949
DOI:10.1111/cns.70045