{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:02:06Z","timestamp":1791907326341,"version":"4.3.4"},"reference-count":84,"publisher":"Society for Neuroscience","issue":"42","license":[{"start":{"date-parts":[[2012,4,19]],"date-time":"2012-04-19T00:00:00Z","timestamp":1334793600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,10,19]]},"abstract":"<jats:p>\n                    Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 (transient receptor potential subtype V1) and TNF-\u03b1, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice lacking\n                    <jats:italic>Trpv1<\/jats:italic>\n                    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)\n                    <jats:italic>in vivo<\/jats:italic>\n                    is abolished in\n                    <jats:italic>Trpv1<\/jats:italic>\n                    knock-out mice. TNF-\u03b1 also increases sEPSC frequency but not amplitude in spinal outer lamina II (lamina IIo) neurons, and this increase is abolished in\n                    <jats:italic>Trpv1<\/jats:italic>\n                    knock-out mice. Single-cell PCR analysis revealed that TNF-\u03b1-responding neurons in lamina IIo are exclusively excitatory (vGluT2\n                    <jats:sup>+<\/jats:sup>\n                    ) neurons. Notably, neuroprotectin-1 (NPD1), an anti-inflammatory lipid mediator derived from \u03c9-3 polyunsaturated fatty acid (docosahexaenoic acid), blocks TNF-\u03b1- and capsaicin-evoked sEPSC frequency increases but has no effect on basal synaptic transmission. Strikingly, NPD1 potently inhibits capsaicin-induced TRPV1 current (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.4 n\n                    <jats:sc>m<\/jats:sc>\n                    ) in dissociated dorsal root ganglion neurons, and this IC\n                    <jats:sub>50<\/jats:sub>\n                    is \u2248500 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\u201310 ng), blocks spinal LTP and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain. NPD1 also reduces TRPV1-independent but TNF-\u03b1-dependent pain hypersensitivity. Our findings demonstrate a novel role of NPD1 in regulating TRPV1\/TNF-\u03b1-mediated spinal synaptic plasticity and identify NPD1 as a novel analgesic for treating inflammatory pain.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2443-11.2011","type":"journal-article","created":{"date-parts":[[2011,10,19]],"date-time":"2011-10-19T17:18:14Z","timestamp":1319044694000},"page":"15072-15085","source":"Crossref","is-referenced-by-count":228,"title":["Resolving TRPV1- and TNF-\u03b1-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin 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