ArticleCNS neuroscience & therapeutics2025
Noradrenergic Locus Coeruleus-CA3 Activation Alleviates Neuropathic Pain and Anxiety- and Depression-Like Behaviors by Suppressing Microglial Neuroinflammation in SNI Mice.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- DNMT1-mediated central amygdala to locus coeruleus circuit contributes to chronic pain-related depression in mice.Acta pharmacologica Sinica · 2026Article
- The Small Molecule Compound Eupalinolide B Ameliorates Depressive Behaviors and Neuropathic Pain in Mice With Spared Nerve Injury: Integrating Network Pharmacology, Molecular Docking, Bioinformatics, Molecular Dynamics Simulation and Experimental Verification.CNS neuroscience & therapeutics · 2026Article
- Shared Mechanisms and Integrated Management of Post-Stroke Pain and Depression: A Comprehensive Review.Pain and therapy · 2026Review
- Microglia-derived neuroinflammatory pathways in neuropathic pain.The Korean journal of pain · 2026Review
- Chronic Hyponatremia Potentiates Innate Anxiety-Like Behaviors Through the Dysfunction of Monoaminergic Neurons in Mice.Molecular neurobiology · 2025Article
- Ginger Moxibustion Activates TRPV1 to Modulate the Locus Coeruleus-Spinal Cord-Uterus Pathway and Alleviates Primary Dysmenorrhea in Rats.Journal of pain research · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
objectiveNeuropathic pain (NP) arises from neuroimmune interactions following nerve injury and is often accompanied by anxiety and depression. The aim of the study is to evaluate the effects of the noradrenergic locus coeruleus (LC), a key regulator of pain and emotional states, projects extensively to the hippocampus.
methodWe investigated the effects of chronic NP on LC integrity and its projections to the hippocampal CA3 region in spared nerve injury (SNI) mice with behavioral tests, immunohistochemistry, neurochemical analyses, and Gq-DREADD.
resultsChronic NP induced LC neuronal loss, reduced hippocampal norepinephrine (NE) release, and triggered microglial activation and neuroinflammation in CA3. Selective activation of LC-CA3 noradrenergic neurons using Gq-DREADD chemogenetics alleviated NP and comorbid anxiety- and depression-like behaviors. This intervention suppressed microglial activation, decreased proinflammatory cytokines (TNF-α and IL-1β), and restored NE levels in CA3.
conclusionOur findings highlighted the therapeutic potential of targeting LC-CA3 projections to mitigate chronic NP and its neuropsychiatric comorbidities via modulation of hippocampal neuroinflammation.
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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 Socratic graph.