ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Chemokine receptor CCR2 contributes to neuropathic pain and the associated depression via increasing NR2B-mediated currents in both D1 and D2 dopamine receptor-containing medium spiny neurons in the nucleus accumbens shell.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Mechanical Compression-Induced Peripheral Neuropathic Pain: From Astrocyte Mechanosensing and Phenotypic Reprogramming to CCL2-CCR2 Axis-Targeted Therapies.Journal of inflammation research · 2026Review
- Adenosine AFrontiers in pharmacology · 2026Article
- Synaptic plasticity in affective comorbidities of neuropathic pain: a bibliometric analysis based on WoSCC and PubMed (2003-2025).Frontiers in neurology · 2026Article
- Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders.Journal of medicinal chemistry · 2025Article
- Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.Neuroscience bulletin · 2025Review
- Focal Adhesion Kinase Inhibition Ameliorates Burn Injury-Induced Chronic Pain in Rats.Molecular neurobiology · 2025Article
- Development of a macrophage polarization-modulating therapeutic agent for osteoarthritis treatment.Journal of orthopaedic surgery and research · 2025Review
- A Neural Circuit From Paraventricular Nucleus of the Thalamus to the Nucleus Accumbens Mediates Inflammatory Pain in Mice.Brain and behavior · 2025Article
- Pain-related cortico-limbic plasticity and opioid signaling.Neuropharmacology · 2023Review
- Magnolin Inhibits Paclitaxel-Induced Cold Allodynia and ERK1/2 Activation in Mice.Plants (Basel, Switzerland) · 2023Article
- Spinal MCP-1 Contributes to Central Post-stroke Pain by Inducing Central Sensitization in Rats.Molecular neurobiology · 2023Article
- Excitatory Projections from the Prefrontal Cortex to Nucleus Accumbens Core D1-MSNs and κ Opioid Receptor Modulate Itch-Related Scratching Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Peripheral CCL2 induces inflammatory pain via regulation ofFrontiers in molecular neuroscience · 2023Article
- Progranulin from different gliocytes in the nucleus accumbens exerts distinct roles in FTD- and neuroinflammation-induced depression-like behaviors.Journal of neuroinflammation · 2022Article
- Ginsenoside Rh2 Ameliorates Neuropathic Pain by inhibition of the miRNA21-TLR8-mitogen-activated protein kinase axis.Molecular pain · 2022Article
- Dopamine Receptors: Is It Possible to Become a Therapeutic Target for Depression?Frontiers in pharmacology · 2022Review
- Dysmyelination by Oligodendrocyte-Specific Ablation of Ninj2 Contributes to Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Targeting the CCL2-CCR2 axis in depressive disorders.Pharmacological reports : PR · 2021Review
- CCL2/CCR2 Contributes to the Altered Excitatory-inhibitory Synaptic Balance in the Nucleus Accumbens Shell Following Peripheral Nerve Injury-induced Neuropathic Pain.Neuroscience bulletin · 2021Article
- Assessment of Growth Factors, Cytokines, and Cellular Markers in Saliva of Patients with Trigeminal Neuralgia.Molecules (Basel, Switzerland) · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Patients with neuropathic pain are usually accompanied by depression. Chemokine-mediated neuroinflammation is involved in a variety of diseases, including neurodegenerative diseases, depression, and chronic pain. The nucleus accumbens (NAc) is an important area in mediating pain sensation and depression. Here we report that spinal nerve ligation (SNL) induced upregulation of chemokine CCL2 and its major receptor CCR2 in both dopamine D1 and D2 receptor (D1R and D2R)-containing neurons in the NAc. Inhibition of CCR2 by shRNA lentivirus in the NAc shell attenuated SNL-induced pain hypersensitivity and depressive behaviors. Conversely, intra-NAc injection of CCL2-expressing lentivirus-induced nociceptive and depressive behaviors in naïve mice. Whole-cell patch clamp recording of D1R-positive or D2R-positive medium spiny neurons (MSNs) showed that SNL increased NMDA receptor (NMDAR)-mediated currents that are induced by stimulation of prefrontal cortical afferents to MSNs, which was inhibited by a CCR2 antagonist. Furthermore, Ccr2 shRNA also reduced NMDAR-mediated currents, and this reduction was mainly mediated via NR2B subunit. Consistently, NR2B, colocalized with CCR2 in the NAc, was phosphorylated after SNL and was inhibited by intra-NAc injection of Ccr2 shRNA. Furthermore, SNL or CCL2 induced ERK activation in the NAc. Inhibition of ERK by a MEK inhibitor reduced NR2B phosphorylation induced by SNL or CCL2. Finally, intra-NAc injection of NR2B antagonist or MEK inhibitor attenuated SNL-induced pain hypersensitivity and depressive behaviors. Collectively, these results suggest that CCL2/CCR2 signaling in the NAc shell is important in mediating neuropathic pain and depression via regulating NR2B-mediated NMDAR function in D1R- and D2R-containing neurons following peripheral nerve injury.
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