Noxious Stimulation Induces Trk Receptor and Downstream ERK Phosphorylation in Spinal Dorsal Horn
Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF) acts as central pain neuromodulator.We examined the ability of different types of peripheral stimulation to activate the BDNF high-affinity receptor, TrkB, in the spinal cord. We found that noxious chemical, mechanic...
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| Veröffentlicht in: | Molecular and cellular neuroscience 2002-12, Vol.21 (4), p.684-695 |
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| creator | Pezet, Sophie Malcangio, Marzia Lever, Isobel J. Perkinton, Michael S. Thompson, Stephen W.N. Williams, Robert J. McMahon, Stephen B. |
| description | Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF) acts as central pain neuromodulator.We examined the ability of different types of peripheral stimulation to activate the BDNF high-affinity receptor, TrkB, in the spinal cord. We found that noxious chemical, mechanical, or thermal stimuli, but not innocuous stimuli, caused Trk phosphorylation in the spinal cord. These changes were rapid and transient and restricted to somatotopically appropriate spinal segments. We observed, both
in vitro and
in vivo, that exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in the development of acute pain. Finally, we found that sequestering BDNF
in vivo with a TrkB-IgG fusion molecule significantly reduced the activation of ERK evoked by noxious stimulation. These data suggest that BDNF, once released with activity from primary afferent nociceptors, exerts a neuromodulatory role in pain processing through stimulation of postsynaptic TrkB receptors and subsequent activation of ERK. |
| doi_str_mv | 10.1006/mcne.2002.1205 |
| format | Article |
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in vitro and
in vivo, that exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in the development of acute pain. Finally, we found that sequestering BDNF
in vivo with a TrkB-IgG fusion molecule significantly reduced the activation of ERK evoked by noxious stimulation. These data suggest that BDNF, once released with activity from primary afferent nociceptors, exerts a neuromodulatory role in pain processing through stimulation of postsynaptic TrkB receptors and subsequent activation of ERK.</description><identifier>ISSN: 1044-7431</identifier><identifier>EISSN: 1095-9327</identifier><identifier>DOI: 10.1006/mcne.2002.1205</identifier><identifier>PMID: 12504600</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Afferent Pathways - drug effects ; Afferent Pathways - metabolism ; Animals ; Animals, Newborn ; Brain-Derived Neurotrophic Factor - metabolism ; Life Sciences ; Male ; Mitogen-Activated Protein Kinases - drug effects ; Mitogen-Activated Protein Kinases - metabolism ; Mustard Plant ; Nerve Fibers, Unmyelinated - drug effects ; Nerve Fibers, Unmyelinated - metabolism ; Neurons and Cognition ; Nociceptors - drug effects ; Nociceptors - metabolism ; Pain - chemically induced ; Pain - metabolism ; Pain - physiopathology ; Pain Measurement ; Phosphorylation ; Physical Stimulation ; Plant Extracts ; Plant Oils ; Posterior Horn Cells - drug effects ; Posterior Horn Cells - metabolism ; Precipitin Tests ; Presynaptic Terminals - drug effects ; Presynaptic Terminals - metabolism ; Rats ; Rats, Wistar ; Receptor, trkB - drug effects ; Receptor, trkB - metabolism ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology</subject><ispartof>Molecular and cellular neuroscience, 2002-12, Vol.21 (4), p.684-695</ispartof><rights>2002 Elsevier Science (USA)</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-87acb9a30d4d3d8f81b6977937f3fa2ee2f34e16951aa91ecaf7095471aa77c23</citedby><orcidid>0000-0002-3305-3315</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/mcne.2002.1205$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,778,782,883,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12504600$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03242288$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Pezet, Sophie</creatorcontrib><creatorcontrib>Malcangio, Marzia</creatorcontrib><creatorcontrib>Lever, Isobel J.</creatorcontrib><creatorcontrib>Perkinton, Michael S.</creatorcontrib><creatorcontrib>Thompson, Stephen W.N.</creatorcontrib><creatorcontrib>Williams, Robert J.</creatorcontrib><creatorcontrib>McMahon, Stephen B.</creatorcontrib><title>Noxious Stimulation Induces Trk Receptor and Downstream ERK Phosphorylation in Spinal Dorsal Horn</title><title>Molecular and cellular neuroscience</title><addtitle>Mol Cell Neurosci</addtitle><description>Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF) acts as central pain neuromodulator.We examined the ability of different types of peripheral stimulation to activate the BDNF high-affinity receptor, TrkB, in the spinal cord. We found that noxious chemical, mechanical, or thermal stimuli, but not innocuous stimuli, caused Trk phosphorylation in the spinal cord. These changes were rapid and transient and restricted to somatotopically appropriate spinal segments. We observed, both
in vitro and
in vivo, that exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in the development of acute pain. Finally, we found that sequestering BDNF
in vivo with a TrkB-IgG fusion molecule significantly reduced the activation of ERK evoked by noxious stimulation. These data suggest that BDNF, once released with activity from primary afferent nociceptors, exerts a neuromodulatory role in pain processing through stimulation of postsynaptic TrkB receptors and subsequent activation of ERK.</description><subject>Afferent Pathways - drug effects</subject><subject>Afferent Pathways - metabolism</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mitogen-Activated Protein Kinases - drug effects</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Mustard Plant</subject><subject>Nerve Fibers, Unmyelinated - drug effects</subject><subject>Nerve Fibers, Unmyelinated - metabolism</subject><subject>Neurons and Cognition</subject><subject>Nociceptors - drug effects</subject><subject>Nociceptors - metabolism</subject><subject>Pain - chemically induced</subject><subject>Pain - metabolism</subject><subject>Pain - physiopathology</subject><subject>Pain Measurement</subject><subject>Phosphorylation</subject><subject>Physical Stimulation</subject><subject>Plant Extracts</subject><subject>Plant Oils</subject><subject>Posterior Horn Cells - drug effects</subject><subject>Posterior Horn Cells - metabolism</subject><subject>Precipitin Tests</subject><subject>Presynaptic Terminals - drug effects</subject><subject>Presynaptic Terminals - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, trkB - drug effects</subject><subject>Receptor, trkB - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><issn>1044-7431</issn><issn>1095-9327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kElPwzAQRi0EYr9yRL5ySBkvqZMjgkIRFSCWs-U6E9XQ2JGdsvx7ErWCE6dZ9L6R5hFywmDEAMbnjfU44gB8xDjkW2SfQZlnpeBqe-ilzJQUbI8cpPQGADkvxS7ZYzwHOQbYJ-Y-fLmwSvS5c81qaToXPL311cpioi_xnT6hxbYLkRpf0avw6VMX0TR08nRHHxchtYsQvzc55-lz67xZ9mBMfZmG6I_ITm2WCY839ZC8Xk9eLqfZ7OHm9vJillkpocsKZey8NAIqWYmqqAs2H5dKlULVojYckddCIhuXOTOmZGhNrfpXpepHpSwXh-RsfXdhlrqNrjHxWwfj9PRipocdCC45L4oP1rOjNWtjSCli_RtgoAevevCqB6968NoHTteBdjVvsPrDNyJ7oFgD2L_44TDqZB16i5WLaDtdBfff7R_x9obu</recordid><startdate>20021201</startdate><enddate>20021201</enddate><creator>Pezet, Sophie</creator><creator>Malcangio, Marzia</creator><creator>Lever, Isobel J.</creator><creator>Perkinton, Michael S.</creator><creator>Thompson, Stephen W.N.</creator><creator>Williams, Robert J.</creator><creator>McMahon, Stephen B.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-3305-3315</orcidid></search><sort><creationdate>20021201</creationdate><title>Noxious Stimulation Induces Trk Receptor and Downstream ERK Phosphorylation in Spinal Dorsal Horn</title><author>Pezet, Sophie ; Malcangio, Marzia ; Lever, Isobel J. ; Perkinton, Michael S. ; Thompson, Stephen W.N. ; Williams, Robert J. ; McMahon, Stephen B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-87acb9a30d4d3d8f81b6977937f3fa2ee2f34e16951aa91ecaf7095471aa77c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Afferent Pathways - drug effects</topic><topic>Afferent Pathways - metabolism</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mitogen-Activated Protein Kinases - drug effects</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Mustard Plant</topic><topic>Nerve Fibers, Unmyelinated - drug effects</topic><topic>Nerve Fibers, Unmyelinated - metabolism</topic><topic>Neurons and Cognition</topic><topic>Nociceptors - drug effects</topic><topic>Nociceptors - metabolism</topic><topic>Pain - chemically induced</topic><topic>Pain - metabolism</topic><topic>Pain - physiopathology</topic><topic>Pain Measurement</topic><topic>Phosphorylation</topic><topic>Physical Stimulation</topic><topic>Plant Extracts</topic><topic>Plant Oils</topic><topic>Posterior Horn Cells - drug effects</topic><topic>Posterior Horn Cells - metabolism</topic><topic>Precipitin Tests</topic><topic>Presynaptic Terminals - drug effects</topic><topic>Presynaptic Terminals - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, trkB - drug effects</topic><topic>Receptor, trkB - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pezet, Sophie</creatorcontrib><creatorcontrib>Malcangio, Marzia</creatorcontrib><creatorcontrib>Lever, Isobel J.</creatorcontrib><creatorcontrib>Perkinton, Michael S.</creatorcontrib><creatorcontrib>Thompson, Stephen W.N.</creatorcontrib><creatorcontrib>Williams, Robert J.</creatorcontrib><creatorcontrib>McMahon, Stephen B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Molecular and cellular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pezet, Sophie</au><au>Malcangio, Marzia</au><au>Lever, Isobel J.</au><au>Perkinton, Michael S.</au><au>Thompson, Stephen W.N.</au><au>Williams, Robert J.</au><au>McMahon, Stephen B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Noxious Stimulation Induces Trk Receptor and Downstream ERK Phosphorylation in Spinal Dorsal Horn</atitle><jtitle>Molecular and cellular neuroscience</jtitle><addtitle>Mol Cell Neurosci</addtitle><date>2002-12-01</date><risdate>2002</risdate><volume>21</volume><issue>4</issue><spage>684</spage><epage>695</epage><pages>684-695</pages><issn>1044-7431</issn><eissn>1095-9327</eissn><abstract>Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF) acts as central pain neuromodulator.We examined the ability of different types of peripheral stimulation to activate the BDNF high-affinity receptor, TrkB, in the spinal cord. We found that noxious chemical, mechanical, or thermal stimuli, but not innocuous stimuli, caused Trk phosphorylation in the spinal cord. These changes were rapid and transient and restricted to somatotopically appropriate spinal segments. We observed, both
in vitro and
in vivo, that exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in the development of acute pain. Finally, we found that sequestering BDNF
in vivo with a TrkB-IgG fusion molecule significantly reduced the activation of ERK evoked by noxious stimulation. These data suggest that BDNF, once released with activity from primary afferent nociceptors, exerts a neuromodulatory role in pain processing through stimulation of postsynaptic TrkB receptors and subsequent activation of ERK.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12504600</pmid><doi>10.1006/mcne.2002.1205</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3305-3315</orcidid></addata></record> |
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| subjects | Afferent Pathways - drug effects Afferent Pathways - metabolism Animals Animals, Newborn Brain-Derived Neurotrophic Factor - metabolism Life Sciences Male Mitogen-Activated Protein Kinases - drug effects Mitogen-Activated Protein Kinases - metabolism Mustard Plant Nerve Fibers, Unmyelinated - drug effects Nerve Fibers, Unmyelinated - metabolism Neurons and Cognition Nociceptors - drug effects Nociceptors - metabolism Pain - chemically induced Pain - metabolism Pain - physiopathology Pain Measurement Phosphorylation Physical Stimulation Plant Extracts Plant Oils Posterior Horn Cells - drug effects Posterior Horn Cells - metabolism Precipitin Tests Presynaptic Terminals - drug effects Presynaptic Terminals - metabolism Rats Rats, Wistar Receptor, trkB - drug effects Receptor, trkB - metabolism Signal Transduction - drug effects Signal Transduction - physiology Synaptic Transmission - drug effects Synaptic Transmission - physiology |
| title | Noxious Stimulation Induces Trk Receptor and Downstream ERK Phosphorylation in Spinal Dorsal Horn |
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