ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Resolving TRPV1- and TNF-α-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed.
- Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain.Breast cancer research and treatment · 2018Trial
- Trial
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Sepsis-associated acute lung injury: do inflammatory lipid mediators flood the lungs by activating pulmonary TRP channels?Intensive care medicine experimental · 2026Review
- Protectin DX reduces inflammatory pain initiated by superoxide anion in mice: targeting leukocyte recruitment, oxidative stress, cytokine production and TRPV1Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Astrocyte-Specific Upregulation of Tumor Necrosis Factor Receptor II Ameliorates Pathological Phenotypes in APPNeuroscience bulletin · 2026Article
- Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.The Journal of clinical investigation · 2026Article
- PGC-1α Transcriptionally Regulated by ChREBP Mitigates Neuropathic Pain Through Promoting Microglial Fatty Acid Oxidation and Anti-Inflammatory Response.CNS neuroscience & therapeutics · 2026Article
- GPR37 activation erases spinal pain memory and resolves increased nociception in murine models.bioRxiv : the preprint server for biology · 2025Article
- Diverse Effects of Various Toll-Like Receptor 2 Ligands on Neuronal Activity and Cell Death.Cellular and molecular neurobiology · 2025Article
- Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain.Cell · 2025Article
- Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation.Prostaglandins, leukotrienes, and essential fatty acids · 2025Article
- TNF-α Enhanced Activity of Sympathetic Neurons in Superior Cervical Ganglion to Promote Chronic Sleep Deprivation-Related Hyperalgesia.Molecular neurobiology · 2025Article
- Neuroprotectin D1 and GPR37 protect against chemotherapy-induced peripheral neuropathy and the transition from acute to chronic pain.Pharmacological research · 2025Article
- Review
- Resolvin D1 accelerates resolution of neuroinflammation by inhibiting microglia activation through the BDNF/TrkB signaling pathway.European journal of medical research · 2025Article
- The mechanisms of specialized pro-resolving mediators in pain relief: neuro-immune and neuroglial regulations.Frontiers in immunology · 2025Review
- Analgesic and Anti-Arthritic Potential of Methanolic Extract and Palmatine Obtained fromPharmaceuticals (Basel, Switzerland) · 2024Article
- Mer activation ameliorates nerve injury-induced neuropathic pain by regulating microglial polarization and neuroinflammation via SOCS3 in male rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Oleic acid released by sensory neurons inhibits TRPV1-mediated thermal hypersensitivity via GPR40.iScience · 2024Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 (transient receptor potential subtype V1) and TNF-α, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice lacking Trpv1 the frequency but not the amplitude of spontaneous EPSCs (sEPSCs) in lamina II neurons of spinal cord slices is reduced. Further, C-fiber-induced spinal long-term potentiation (LTP) in vivo is abolished in Trpv1 knock-out mice. TNF-α also increases sEPSC frequency but not amplitude in spinal outer lamina II (lamina IIo) neurons, and this increase is abolished in Trpv1 knock-out mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2(+)) neurons. Notably, neuroprotectin-1 (NPD1), an anti-inflammatory lipid mediator derived from ω-3 polyunsaturated fatty acid (docosahexaenoic acid), blocks TNF-α- and capsaicin-evoked sEPSC frequency increases but has no effect on basal synaptic transmission. Strikingly, NPD1 potently inhibits capsaicin-induced TRPV1 current (IC(50) = 0.4 nm) in dissociated dorsal root ganglion neurons, and this IC(50) is ≈ 500 times lower than that of AMG9810, a commonly used TRPV1 antagonist. NPD1 inhibition of TRPV1 is mediated by GPCRs, since the effects were blocked by pertussis toxin. In contrast, NPD1 had no effect on mustard oil-induced TRPA1 currents. Spinal injection of NPD1, at very low doses (0.1-10 ng), blocks spinal LTP and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain. NPD1 also reduces TRPV1-independent but TNF-α-dependent pain hypersensitivity. Our findings demonstrate a novel role of NPD1 in regulating TRPV1/TNF-α-mediated spinal synaptic plasticity and identify NPD1 as a novel analgesic for treating inflammatory pain.
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