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Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1
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| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | The Journal of Neuroscience, 31, 2011, 42, S. 15072-15085 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| author_facet |
Park, Chul-Kyu Lü, Ning Xu, Zhen-Zhong Liu, Tong Serhan, Charles N. Ji, Ru-Rong Park, Chul-Kyu Lü, Ning Xu, Zhen-Zhong Liu, Tong Serhan, Charles N. Ji, Ru-Rong |
|---|---|
| author |
Park, Chul-Kyu Lü, Ning Xu, Zhen-Zhong Liu, Tong Serhan, Charles N. Ji, Ru-Rong |
| spellingShingle |
Park, Chul-Kyu Lü, Ning Xu, Zhen-Zhong Liu, Tong Serhan, Charles N. Ji, Ru-Rong The Journal of Neuroscience Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 General Neuroscience |
| author_sort |
park, chul-kyu |
| spelling |
Park, Chul-Kyu Lü, Ning Xu, Zhen-Zhong Liu, Tong Serhan, Charles N. Ji, Ru-Rong 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2443-11.2011 <jats:p>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<jats:italic>Trpv1</jats:italic>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)<jats:italic>in vivo</jats:italic>is abolished in<jats:italic>Trpv1</jats:italic>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<jats:italic>Trpv1</jats:italic>knock-out mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2<jats:sup>+</jats:sup>) 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<jats:sub>50</jats:sub>= 0.4 n<jats:sc>m</jats:sc>) in dissociated dorsal root ganglion neurons, and this IC<jats:sub>50</jats:sub>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.</jats:p> Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 The Journal of Neuroscience |
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Society for Neuroscience, 2011 |
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| title |
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_unstemmed |
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_full |
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_fullStr |
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_full_unstemmed |
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_short |
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_sort |
resolving trpv1- and tnf-α-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin d1 |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.2443-11.2011 |
| publishDate |
2011 |
| physical |
15072-15085 |
| description |
<jats:p>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<jats:italic>Trpv1</jats:italic>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)<jats:italic>in vivo</jats:italic>is abolished in<jats:italic>Trpv1</jats:italic>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<jats:italic>Trpv1</jats:italic>knock-out mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2<jats:sup>+</jats:sup>) 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<jats:sub>50</jats:sub>= 0.4 n<jats:sc>m</jats:sc>) in dissociated dorsal root ganglion neurons, and this IC<jats:sub>50</jats:sub>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.</jats:p> |
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| author | Park, Chul-Kyu, Lü, Ning, Xu, Zhen-Zhong, Liu, Tong, Serhan, Charles N., Ji, Ru-Rong |
| author_facet | Park, Chul-Kyu, Lü, Ning, Xu, Zhen-Zhong, Liu, Tong, Serhan, Charles N., Ji, Ru-Rong, Park, Chul-Kyu, Lü, Ning, Xu, Zhen-Zhong, Liu, Tong, Serhan, Charles N., Ji, Ru-Rong |
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| description | <jats:p>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<jats:italic>Trpv1</jats:italic>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)<jats:italic>in vivo</jats:italic>is abolished in<jats:italic>Trpv1</jats:italic>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<jats:italic>Trpv1</jats:italic>knock-out mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2<jats:sup>+</jats:sup>) 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<jats:sub>50</jats:sub>= 0.4 n<jats:sc>m</jats:sc>) in dissociated dorsal root ganglion neurons, and this IC<jats:sub>50</jats:sub>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.</jats:p> |
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| imprint | Society for Neuroscience, 2011 |
| imprint_str_mv | Society for Neuroscience, 2011 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Park, Chul-Kyu Lü, Ning Xu, Zhen-Zhong Liu, Tong Serhan, Charles N. Ji, Ru-Rong 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2443-11.2011 <jats:p>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<jats:italic>Trpv1</jats:italic>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)<jats:italic>in vivo</jats:italic>is abolished in<jats:italic>Trpv1</jats:italic>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<jats:italic>Trpv1</jats:italic>knock-out mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2<jats:sup>+</jats:sup>) 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<jats:sub>50</jats:sub>= 0.4 n<jats:sc>m</jats:sc>) in dissociated dorsal root ganglion neurons, and this IC<jats:sub>50</jats:sub>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.</jats:p> Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 The Journal of Neuroscience |
| spellingShingle | Park, Chul-Kyu, Lü, Ning, Xu, Zhen-Zhong, Liu, Tong, Serhan, Charles N., Ji, Ru-Rong, The Journal of Neuroscience, Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1, General Neuroscience |
| title | Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_full | Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_fullStr | Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_full_unstemmed | Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_short | Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| title_sort | resolving trpv1- and tnf-α-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin d1 |
| title_unstemmed | Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1 |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.2443-11.2011 |