ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Activation of Src-family kinases in spinal microglia contributes to mechanical hypersensitivity after nerve injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 143 citations in OpenAlex.
- Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
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- Gender differences in Alzheimer's may be associated with TLR4-LYN expression in damage associated microglia and neuronal phagocytosis.Journal of cellular physiology · 2024Article
- Macrophages and microglia in inflammation and neuroinflammation underlying different pain states.Medical review (2021) · 2023Article
- The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review.Journal of pain research · 2023Review
- Role of Src kinase in regulating protein kinase C mediated phosphorylation of TRPV1.European journal of pain (London, England) · 2022Article
- Normalization of Neuroinflammation: A New Strategy for Treatment of Persistent Pain and Memory/Emotional Deficits in Chronic Pain.Journal of inflammation research · 2022Review
- Immune-Triggered Forms of Plasticity Across Brain Regions.Frontiers in cellular neuroscience · 2022Review
- Emerging Role of PD-1 in the Central Nervous System and Brain Diseases.Neuroscience bulletin · 2021Review
- Systemic inflammation suppresses spinal respiratory motor plasticity via mechanisms that require serine/threonine protein phosphatase activity.Journal of neuroinflammation · 2021Article
- Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.Current neuropharmacology · 2021Article
- A Src family kinase maintains latent sensitization in rats, a model of inflammatory and neuropathic pain.Brain research · 2020Article
- Transient receptor potential vanilloid type 1 is expressed in the horizontal pathway of the vervet monkey retina.Scientific reports · 2020Article
- Bioinformatic Analysis of Neuroimmune Mechanism of Neuropathic Pain.BioMed research international · 2020Article
- Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain.Neuron · 2018Review
- A state-of-the-art perspective on microgliopathic pain.Open biology · 2018Review
- Article
- A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance and Hyperalgesia: A Review.Pain and therapy · 2018Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypersensitivity to mechanical stimulation is a well documented symptom of neuropathic pain, for which there is currently no effective therapy. Src-family kinases (SFKs) are involved in proliferation and differentiation and in neuronal plasticity, including long-term potentiation, learning, and memory. Here we show that activation of SFKs induced in spinal cord microglia is crucial for mechanical hypersensitivity after peripheral nerve injury. Nerve injury induced a striking increase in SFK phosphorylation in the ipsilateral dorsal horn, and SFKs were activated in hyperactive microglia but not in neurons or astrocytes. Intrathecal administration of the Src-family tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) suppressed nerve injury-induced mechanical hypersensitivity but not heat and cold hypersensitivity. Furthermore, PP2 reversed the activation of extracellular signal-regulated protein kinase (ERK), but not p38 mitogen-activated protein kinase, in spinal microglia. In contrast, there was no change in SFK phosphorylation in primary sensory neurons, and PP2 did not decrease the induction of transient receptor potential ion channel TRPV1 and TRPA1 in sensory neurons. Together, these results demonstrate that SFK activation in spinal microglia contributes to the development of mechanical hypersensitivity through the ERK pathway. Therefore, preventing the activation of the Src/ERK signaling cascade in microglia might provide a fruitful strategy for treating neuropathic pain.
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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.