ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 272 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Cannabinoid type 2 receptor crosstalk and microglial plasticity-shaping the balance between neuroinflammation and repair.Inflammopharmacology · 2026Review
- The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain.Purinergic signalling · 2025Review
- How microglia contribute to the induction and maintenance of neuropathic pain.Nature reviews. Neuroscience · 2025Review
- Molecular Anatomy of Synaptic and Extrasynaptic Neurotransmission Between Nociceptive Primary Afferents and Spinal Dorsal Horn Neurons.International journal of molecular sciences · 2025Review
- Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.Brain sciences · 2024Review
- Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache.Molecular and cellular biochemistry · 2023Review
- Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Macrophages and microglia in inflammation and neuroinflammation underlying different pain states.Medical review (2021) · 2023Article
- Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders.Brain sciences · 2023Article
- Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain.Neural regeneration research · 2023Review
- ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain.Science advances · 2023Article
- Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain.Neuroscience bulletin · 2023Review
- The mTOR inhibitor rapamycin suppresses trigeminal neuropathic pain and p-MKK4/p-p38 mitogen-activated protein kinase-mediated microglial activation in the trigeminal nucleus caudalis of mice with infraorbital nerve injury.Frontiers in molecular neuroscience · 2023Article
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Estradiol Treatment Enhances Behavioral and Molecular Changes Induced by Repetitive Trigeminal Activation in a Rat Model of Migraine.Biomedicines · 2022Article
- Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity.Molecular brain · 2022Article
- The Role of ATP Receptors in Pain Signaling.Neurochemical research · 2022Review
- The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury.Cells · 2022Review
- The Multifaceted Role of GPCRs in Amyotrophic Lateral Sclerosis: A New Therapeutic Perspective?International journal of molecular sciences · 2022Review
78 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglia in the spinal cord may play an important role in the development and maintenance of neuropathic pain. A metabotropic ATP receptor, P2Y(12), has been shown to be expressed in spinal microglia constitutively and be involved in chemotaxis. Activation of p38 mitogen-activated protein kinase (MAPK) occurs in spinal microglia after nerve injury and may be related to the production of cytokines and other mediators, resulting in neuropathic pain. However, it remains unknown whether any type of P2Y receptor in microglia is involved in the activation of p38 MAPK and the pain behaviors after nerve injury. Using the partial sciatic nerve ligation (PSNL) model in the rat, we found that P2Y(12) mRNA and protein increased in the spinal cord and peaked at 3 d after PSNL. Double labeling studies revealed that cells expressing increased P2Y(12) mRNA and protein after nerve injury were exclusively microglia. Both pharmacological blockades by intrathecal administration of P2Y(12) antagonist and antisense knockdown of P2Y(12) expression suppressed the development of pain behaviors and the phosphorylation of p38 MAPK in spinal microglia after PSNL. The intrathecal infusion of the P2Y(12) agonist 2-(methythio) adenosine 5'-diphosphate trisodium salt into naive rats mimicked the nerve injury-induced activation of p38 in microglia and elevated pain behaviors. These data suggest a new mechanism of neuropathic pain, in which the increased P2Y(12) works as a gateway of the following events in microglia after nerve injury. Activation of this receptor by released ATP or the hydrolyzed products activate p38 MAPK pathway and may play a crucial role in the generation of neuropathic pain.
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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.