ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
331 citing papers in PubMed, 553 citations in OpenAlex.
- Protective Effect of the MCP-1 Gene Haplotype against Schizophrenia.BioMed research international · 2019Trial
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Nucleolin promotes neuropathic pain by increasing chromatin accessibility at the Ccl2 promoter in primary sensory neurons.Brain, behavior, and immunity · 2026Article
- Reactive aldehyde species-mediated neuropathic pain in spinal cord injury: Mechanisms and therapeutic opportunities.Neural regeneration research · 2026Article
- Meditations on Methodological Issues in Clinical Investigations of "Central Sensitization" (Jonah XII).Journal of clinical medicine · 2026Article
- Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling.Cellular and molecular neurobiology · 2026Article
- Commentary on "Prevalence of Central Sensitization in Notalgia Paresthetica Patients and Its Association with Vertebral Degeneration: A Cross-sectional Study".Acta dermato-venereologica · 2026Article
- RNA-binding protein MBNL2 mitigates neuropathic pain after chemotherapy through destabilizing CCR2 expression in primary sensory neurons.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Contribution of proneurotrophin-3 to nerve trauma-induced neuropathic pain through promoting TrkC-mediated increase of CCL2 in primary sensory neurons.Brain, behavior, and immunity · 2026Article
- Neuroinflammatory Biomarkers in Chronic Low Back Pain: Mechanisms, Clinical Evidence, and Translational Challenges.Biomedicines · 2026Review
- Mechanical Compression-Induced Peripheral Neuropathic Pain: From Astrocyte Mechanosensing and Phenotypic Reprogramming to CCL2-CCR2 Axis-Targeted Therapies.Journal of inflammation research · 2026Review
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Immune profiling in trigeminal neuralgia reveals altered cytokine and chemokine signatures in cerebrospinal fluid and serum.Frontiers in pharmacology · 2026Article
- The pivotal role of immunometabolism in diabetic neuropathy and its potential therapeutic strategies.Frontiers in endocrinology · 2026Review
- Proneurotrophin-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons.EMBO reports · 2025Article
- Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.Neuroscience bulletin · 2025Review
- The CCL17/CCL22-CCR4 Axis in Pain Pathogenesis: A Comprehensive Review of Immune-Mediated Mechanisms and Therapeutic Opportunities.Molecular neurobiology · 2025Review
- Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms.World journal of diabetes · 2025Review
- Electroacupuncture Alleviates Neuropathic Pain by Inhibiting Spinal CCL2-Driven Microglial Activation.International journal of molecular sciences · 2025Article
- Long-Term Clinical and Molecular Changes in Dry Eye Disease and Chronic Ocular Pain.International journal of molecular sciences · 2025Article
271 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.