ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2017
The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
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- Bioinformatics-based identification of potential genes in the thalamus associated with chronic orofacial and somatic inflammatory pain.Frontiers in neuroscience · 2026Article
- Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.Neuroscience bulletin · 2025Review
- Emerging treatments for chronic neuropathic pain from a cross-disease perspective: developments and applications of nanomaterials.The journal of headache and pain · 2025Review
- Unraveling proteomic signatures and neuroinflammatory networks in a CCI rat model of early sciatica: insights for neuropathic pain mechanisms.Frontiers in molecular neuroscience · 2025Article
- A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model.International journal of molecular sciences · 2024Article
- Interleukin‑18 binding protein: Biological properties and roles in human and animal immune regulation (Review).Biomedical reports · 2024Review
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.Molecules (Basel, Switzerland) · 2023Review
- Sustained Hyperammonemia Activates NF-κB in Purkinje Neurons Through Activation of the TrkB-PI3K-AKT Pathway by Microglia-Derived BDNF in a Rat Model of Minimal Hepatic Encephalopathy.Molecular neurobiology · 2023Article
- Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain.Brain sciences · 2023Article
- Pharmacological Modulation of the MIP-1 Family and Their Receptors Reduces Neuropathic Pain Symptoms and Influences Morphine Analgesia: Evidence from a Mouse Model.Brain sciences · 2023Article
- Article
- CC Chemokine Receptor 4 (CCR4) as a Possible New Target for Therapy.International journal of molecular sciences · 2022Review
- Enhanced BDNF and TrkB Activation Enhance GABA Neurotransmission in Cerebellum in Hyperammonemia.International journal of molecular sciences · 2022Article
- Targeting Chemokines and Chemokine GPCRs to Enhance Strong Opioid Efficacy in Neuropathic Pain.Life (Basel, Switzerland) · 2022Review
- Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications.Frontiers in immunology · 2022Review
- CCR2Frontiers in immunology · 2022Article
- New insights into the analgesic properties of the XCL1/XCR1 and XCL1/ITGA9 axes modulation under neuropathic pain conditions - evidence from animal studies.Frontiers in immunology · 2022Article
- Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn.Journal of neuroinflammation · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence has indicated that activated glial cells releasing nociceptive factors, such as interleukins and chemokines, are of key importance for neuropathic pain. Significant changes in the production of nociceptive factors are associated with the low effectiveness of opioids in neuropathic pain. Recently, it has been suggested that CCL2/CCR2 signaling is important for nociception. Here, we studied the time course changes in the mRNA/protein level of CD40/Iba-1, CCL2 and CCR2 in the spinal cord/dorsal root ganglia (DRG) in rats following chronic constriction injury (CCI) of the sciatic nerve. Moreover, we examined the influence of intrathecal preemptive and repeated (daily for 7 days) administration of RS504393, CCR2 antagonist, on pain-related behavior and the associated biochemical changes of some nociceptive factors as well as its influence on opioid effectiveness. We observed simultaneous upregulation of Iba-1, CCL2, CCR2 in the spinal cord on 7th day after CCI. Additionally, we demonstrated that repeated administration of RS504393 not only attenuated tactile/thermal hypersensitivity but also enhanced the analgesic properties of morphine and buprenorphine under neuropathy. Our results proof that repeated administration of RS504393 reduced the mRNA and/or protein levels of pronociceptive factors, such as IL-1beta, IL-18, IL-6 and inducible nitric oxide synthase (iNOS), and some of their receptors in the spinal cord and/or DRG. Furthermore, RS504393 elevated the spinal protein level of antinociceptive IL-1alpha and IL-18 binding protein. Our data provide new evidence that CCR2 is a promising target for diminishing neuropathic pain and enhancing the opioid analgesic effects.
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