ArticleGlia2011
Following nerve injury neuregulin-1 drives microglial proliferation and neuropathic pain via the MEK/ERK pathway.
Article in Glia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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The trial behind it
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Who cites it
66 citing papers in PubMed, 110 citations in OpenAlex.
- NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Review
- Coronary Microvascular Dysfunction: Epidemiology, Pathophysiology, Diagnosis, and Treatment.MedComm · 2026Review
- Transcriptome of the human C2 dorsal root ganglia in C1-2 arthrodesis surgery: insight for neck pain.Brain : a journal of neurology · 2026Article
- Article
- A Sleeping Opportunity Does Not Restore Hippocampal Alterations Induced by 10 Days of Sleep Restriction in Rats.Neurochemical research · 2025Article
- 4E-BP1-dependent translation in microglia controls mechanical hypersensitivity in male and female mice.The Journal of clinical investigation · 2025Article
- Genome-wide association reveals a locus in neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain.iScience · 2024Article
- Article
- Macrophages and microglia in inflammation and neuroinflammation underlying different pain states.Medical review (2021) · 2023Article
- Insular cortex stimulation alleviates neuropathic pain via ERK phosphorylation in neurons.CNS neuroscience & therapeutics · 2023Article
- Microglial Cannabinoid CBInternational journal of molecular sciences · 2023Review
- Electroacupuncture attenuates spared nerve injury-induced neuropathic pain possibly by promoting the progression of AMPK/mTOR-mediated autophagy in spinal microglia.Annals of translational medicine · 2022Article
- Electroacupuncture alleviates neuropathic pain caused by spared nerve injury by promoting AMPK/mTOR-mediated autophagy in dorsal root ganglion macrophage.Annals of translational medicine · 2022Article
- Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy andActa biochimica et biophysica Sinica · 2022Article
- MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.Neuro-oncology · 2022Review
- The Roles of Imaging Biomarkers in the Management of Chronic Neuropathic Pain.International journal of molecular sciences · 2022Review
- Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice.Neuroscience bulletin · 2022Article
6 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
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Following peripheral nerve injury microglia accumulate within the spinal cord and adopt a proinflammatory phenotype a process which contributes to the development of neuropathic pain. We have recently shown that neuregulin-1, a growth factor released following nerve injury, activates erbB 2, 3, and 4 receptors on microglia and stimulates proliferation, survival and chemotaxis of these cells. Here we studied the intracellular signaling pathways downstream of neuregulin-1-erbB activation in microglial cells. We found that neuregulin-1 in vitro induced phosphorylation of ERK1/2 and Akt without activating p38MAPK. Using specific kinase inhibitors we found that the mitogenic effect of neuregulin-1 on microglia was dependant on MEK/ERK1/2 pathway, the chemotactic effect was dependant on PI3K/Akt signaling and survival was dependant on both pathways. Intrathecal treatment with neuregulin-1 was associated with microgliosis and development of mechanical and cold pain related hypersensitivity which was dependant on ERK1/2 phosphorylation in microglia. Spinal nerve ligation results in a robust microgliosis and sustained ERK1/2 phosphorylation within these cells. This pathway is downstream of neuregulin-1/erbB signaling since its blockade resulted in a significant reduction in microglial ERK1/2 phosphorylation. Inhibition of the MEK/ERK1/2 pathway resulted in decreased spinal microgliosis and in reduced mechanical and cold hypersensitivity after peripheral nerve damage. We conclude that neuregulin-1 released after nerve injury activates microglial erbB receptors which consequently stimulates the MEK/ERK1/2 pathway that drives microglial proliferation and contributes to the development of neuropathic pain.
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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.