ArticleJournal of neuroinflammation2012
Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling.Cellular and molecular neurobiology · 2026Article
- The function of chemokine-driven glial-neuronal interaction in chronic pain.Frontiers in neuroscience · 2026Review
- Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.Neuroscience bulletin · 2025Review
- The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.Biomedicines · 2025Review
- Dynamics of Cellular Regulation of Fractalkine/CX3CL1 and Its Receptor CX3CR1 in the Rat Trigeminal Subnucleus Caudalis after Unilateral Infraorbital Nerve Lesion-Extended Cellular Signaling of the CX3CL1/CX3CR1 Axis in the Development of Trigeminal Neuropathic Pain.International journal of molecular sciences · 2024Article
- 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
- Review
- GFAP-NpHR mediated optogenetic inhibition of trigeminal nucleus caudalis attenuates hypersensitive behaviors and thalamic discharge attributed to infraorbital nerve constriction injury.The journal of headache and pain · 2023Article
- Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization.Brain : a journal of neurology · 2023Article
- Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.Molecules (Basel, Switzerland) · 2023Review
- Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Pathophysiology of Post-Traumatic Trigeminal Neuropathic Pain.Biomolecules · 2022Review
- Neuroinflammation Involved in Diabetes-Related Pain and Itch.Frontiers in pharmacology · 2022Review
- Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury.Journal of neuroinflammation · 2021Article
- Are glia targets for neuropathic orofacial pain therapy?Journal of the American Dental Association (1939) · 2021Article
- Mechanistic insights into the role of the chemokine CCL2/CCR2 axis in dorsal root ganglia to peripheral inflammation and pain hypersensitivity.Journal of neuroinflammation · 2021Article
- Chemokines and Pain in the Trigeminal System.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Systems and Circuits Linking Chronic Pain and Circadian Rhythms.Frontiers in neuroscience · 2021Review
- Reactive Astrocytes: Critical Players in the Development of Chronic Pain.Frontiers in psychiatry · 2021Review
- CXCL10 and CXCR3 in the Trigeminal Ganglion Contribute to Trigeminal Neuropathic Pain in Mice.Journal of pain research · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2)-chemokine C-C motif receptor 2 (CCR2) signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain.
methodsThe inferior alveolar nerve and mental nerve transection (IAMNT) was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP), and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing.
resultsIAMNT induced persistent (>21 days) heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH) from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg) significantly attenuated IAMNT-induced heat hyperalgesia.
conclusionThe data suggest that CCL2-CCR2 signaling may be involved in the maintenance of orofacial neuropathic pain via astroglial-neuronal interaction. Targeting CCL2-CCR2 signaling may be a potentially important new treatment strategy for trigeminal neuralgia.
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