ArticleMolecular neurobiology2024
CCL2 Potentiates Inflammation Pain and Related Anxiety-Like Behavior Through NMDA Signaling in Anterior Cingulate Cortex.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- A systematic review of preclinical studies targeted toward the management of co-existing functional gastrointestinal disorders, stress, and gut dysbiosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Pooled it
- TREM-1-dependent macrophage infiltration mediates visceral hypersensitivity via vlPAG GABAergic neuron activation in a mouse model of inflammatory bowel disease.Cellular & molecular biology letters · 2026Article
- Mrgprb4-Lineage Neurons Participate in the Intervention of TENS Effects on Chronic Pain and Anxiety-like Symptoms in an Inflammatory Pain Mouse Model.Biomedicines · 2026Article
- Manual Massage Therapy for Neuropathic Pain: Clinical Evidence and Mechanistic Insights.Pain research & management · 2026Review
- Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.Neuroscience bulletin · 2025Review
- Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances.International journal of molecular sciences · 2025Review
- Methylation levels in the GRIN2B promoter region are associated with bipolar disorder and its anxiety and insomnia symptoms.Experimental and therapeutic medicine · 2025Article
- Immune control of brain physiology.Nature reviews. Immunology · 2025Review
- Mitofusin 2 Mediates the Protective Effect of NR6A1 Silencing Against Neuronal Injury in Experimental Stroke Models.Molecular neurobiology · 2025Article
- [Enriched environment reduces pyramidal neuron excitability in the anterior cingulate cortex to alleviate restraint stress-induced anxiety-like behaviors in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Previous studies have shown that the C-C motif chemokine ligand 2 (CCL2) is widely expressed in the nervous system and involved in regulating the development of chronic pain and related anxiety-like behaviors, but its precise mechanism is still unclear. This paper provides an in-depth examination of the involvement of CCL2-CCR2 signaling in the anterior cingulate cortex (ACC) in intraplantar injection of complete Freund's adjuvant (CFA) leading to inflammatory pain and its concomitant anxiety-like behaviors by modulation of glutamatergic N-methyl-D-aspartate receptor (NMDAR). Our findings suggest that local bilateral injection of CCR2 antagonist in the ACC inhibits CFA-induced inflammatory pain and anxiety-like behavior. Meanwhile, the expression of CCR2 and CCL2 was significantly increased in ACC after 14 days of intraplantar injection of CFA, and CCR2 was mainly expressed in excitatory neurons. Whole-cell patch-clamp recordings showed that the CCR2 inhibitor RS504393 reduced the frequency of miniature excitatory postsynaptic currents (mEPSC) in ACC, and CCL2 was involved in the regulation of NMDAR-induced current in ACC neurons in the pathological state. In addition, local injection of the NR2B inhibitor of NMDAR subunits, Ro 25-6981, attenuated the effects of CCL2-induced hyperalgesia and anxiety-like behavior in the ACC. In summary, CCL2 acts on CCR2 in ACC excitatory neurons and participates in the regulation of CFA-induced pain and related anxiety-like behaviors through upregulation of NR2B. CCR2 in the ACC neuron may be a potential target for the treatment of chronic inflammatory pain and pain-related anxiety.
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Registered trials
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