{"corpus_id":14558765,"paper_sha":"de1113dc47a1628cc21ab985d471240bfe2b4f9a","doi":"10.1523/JNEUROSCI.3686-05.2006","arxiv_id":null,"pmid":16399679,"pmcid":"PMC6674294","mag_id":2131110619,"dblp_id":null,"acl_id":null,"title":"Supraspinal Brain-Derived Neurotrophic Factor Signaling: A Novel Mechanism for Descending Pain Facilitation","year":2006,"publication_date":"2006-01-04","venue":"Journal of Neuroscience","journal":{"name":"The Journal of Neuroscience","pages":"126 - 137","volume":"26"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle","Study"],"pubmed_pub_types":["Comparative Study","Journal Article","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":53,"citation_count":191,"influential_citation_count":18,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Brain-Derived Neurotrophic Factor","mj":false,"qs":[{"q":"biosynthesis","mj":false,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D019208"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Medulla Oblongata","mj":false,"qs":[{"q":"enzymology","mj":false,"ui":"Q000201"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D008526"},{"d":"Pain","mj":false,"qs":[{"q":"enzymology","mj":false,"ui":"Q000201"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D010146"},{"d":"Pain Measurement","mj":false,"qs":[{"q":"methods","mj":false,"ui":"Q000379"}],"ui":"D010147"},{"d":"Pyramidal Tracts","mj":false,"qs":[{"q":"enzymology","mj":false,"ui":"Q000201"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D011712"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Receptor, trkB","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D020813"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D015398"}],"chemicals":[{"n":"Brain-Derived Neurotrophic Factor","ui":"D019208","reg":"0"},{"n":"Receptor, trkB","ui":"D020813","reg":"EC 2.7.10.1"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.jneurosci.org/content/jneuro/26/1/126.full.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/de1113dc47a1628cc21ab985d471240bfe2b4f9a","s2_open_access_license":"CCBYNCSA","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"In the adult mammalian brain, brain-derived neurotrophic factor (BDNF) is critically involved in long-term synaptic plasticity. Here, we show that supraspinal BDNF-tyrosine kinase receptor B (TrkB) signaling contributes to pain facilitation. We show that BDNF-containing neurons in the periaqueductal gray (PAG), the central structure for pain modulation, project to and release BDNF in the rostral ventromedial medulla (RVM), a relay between the PAG and spinal cord. BDNF in PAG and TrkB phosphorylation in RVM neurons are upregulated after inflammation. Intra-RVM sequestration of BDNF and knockdown of TrkB by RNA interference attenuate inflammatory pain. Microinjection of BDNF (10–100 fmol) into the RVM facilitates nociception, which is dependent on NMDA receptors (NMDARs). In vitro studies with RVM slices show that BDNF induces tyrosine phosphorylation of the NMDAR NR2A subunit in RVM via a signal transduction cascade involving IP3, PKC, and Src. The supraspinal BDNF-TrkB signaling represents a previously unknown mechanism underlying the development of persistent pain. Our findings also caution that application of BDNF for recovery from CNS disorders could lead to undesirable central pain.","claims":[{"public_id":"cl_13045de09c5175e3d39e5ec52c9153fa","status":"active","text":"BDNF in the periaqueductal gray and TrkB phosphorylation in rostral ventromedial medulla neurons are upregulated after inflammation.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_13045de09c5175e3d39e5ec52c9153fa"},{"public_id":"cl_05cd12acf5d1223bcf247f6eb5949a4c","status":"active","text":"BDNF induces tyrosine phosphorylation of the NMDA receptor NR2A subunit in rostral ventromedial medulla slices via an IP3-, PKC-, and Src-dependent cascade.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_05cd12acf5d1223bcf247f6eb5949a4c"},{"public_id":"cl_0ae280158e2dbcbca4e0b63f4f4c23b2","status":"active","text":"BDNF microinjection into the rostral ventromedial medulla facilitates nociception through an NMDA receptor-dependent mechanism.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_0ae280158e2dbcbca4e0b63f4f4c23b2"},{"public_id":"cl_242ef6311462a0ed06de2d8685066440","status":"active","text":"BDNF-containing neurons in the periaqueductal gray project to the rostral ventromedial medulla and release BDNF there.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_242ef6311462a0ed06de2d8685066440"},{"public_id":"cl_170ee16d04cef3a25221364c19bec52a","status":"active","text":"Intra-rostral ventromedial medulla sequestration of BDNF and TrkB knockdown attenuate inflammatory pain.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_170ee16d04cef3a25221364c19bec52a"},{"public_id":"cl_286005e2f6864fdd686f3259c16b7235","status":"active","text":"Supraspinal BDNF-TrkB signaling contributes to pain facilitation.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_286005e2f6864fdd686f3259c16b7235"}],"concepts":[{"public_id":"co_0424fd3e58a125c218a0bdc5663b6db8","status":"active","name":"periaqueductal gray","description":"A midbrain structure that serves as a key center for pain modulation.","types":["brain region"],"aliases":["PAG"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0424fd3e58a125c218a0bdc5663b6db8"},{"public_id":"co_0d7d0e6cb8222d232e77d9e84dea6abd","status":"active","name":"BDNF sequestration","description":"Experimental removal or binding of BDNF to prevent its signaling activity.","types":["experimental intervention"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0d7d0e6cb8222d232e77d9e84dea6abd"},{"public_id":"co_112bb456449ff1a4e7f614e5e956d8ac","status":"active","name":"NMDA receptors","description":"Glutamatergic receptors that mediate excitatory synaptic transmission.","types":["receptor"],"aliases":["NMDARs"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_112bb456449ff1a4e7f614e5e956d8ac"},{"public_id":"co_22cd618027fc3aa54a06c21eec2398ef","status":"active","name":"NMDA receptor NR2A subunit","description":"A subunit of the NMDA receptor complex targeted by phosphorylation in the reported signaling cascade.","types":["protein subunit"],"aliases":["NR2A"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_22cd618027fc3aa54a06c21eec2398ef"},{"public_id":"co_297b56d877ef929f934e329da74d479d","status":"active","name":"IP3, PKC, and Src cascade","description":"An intracellular signal transduction cascade involving IP3, protein kinase C, and Src kinase.","types":["signaling cascade"],"aliases":["IP3","PKC","Src"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_297b56d877ef929f934e329da74d479d"},{"public_id":"co_36bb1a2ae355032e7d3fd190cd22c271","status":"active","name":"BDNF-containing neurons","description":"Neurons that contain and can release brain-derived neurotrophic factor.","types":["cell type"],"aliases":["BDNF neurons"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_36bb1a2ae355032e7d3fd190cd22c271"},{"public_id":"co_5113e8c4bbbedb4605b53fc729aa2811","status":"active","name":"BDNF","description":"Brain-derived neurotrophic factor, a neurotrophin involved in neuronal signaling.","types":["molecule"],"aliases":["brain-derived neurotrophic factor"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5113e8c4bbbedb4605b53fc729aa2811"},{"public_id":"co_83b41482c72bd74f16a920413e6e821a","status":"active","name":"TrkB knockdown","description":"Reduction of TrkB expression using RNA interference.","types":["experimental intervention"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_83b41482c72bd74f16a920413e6e821a"},{"public_id":"co_997cc6ebbcbfe590e2c716c0165aa17b","status":"active","name":"supraspinal BDNF-TrkB signaling","description":"Brain-derived neurotrophic factor signaling through the TrkB receptor at supraspinal sites involved in pain modulation.","types":["signaling pathway"],"aliases":["supraspinal BDNF-tyrosine kinase receptor B signaling"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_997cc6ebbcbfe590e2c716c0165aa17b"},{"public_id":"co_a4be41d9bba20b4387190037144f78b2","status":"active","name":"pain facilitation","description":"Enhancement of pain signaling or pain sensitivity.","types":["phenomenon"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a4be41d9bba20b4387190037144f78b2"},{"public_id":"co_bdc7354fce51b14842a3867b3d295d22","status":"active","name":"TrkB phosphorylation","description":"Phosphorylation of the TrkB receptor, indicating receptor activation.","types":["molecular event"],"aliases":["tyrosine kinase receptor B phosphorylation"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_bdc7354fce51b14842a3867b3d295d22"},{"public_id":"co_ca40acd8c7c25d8fac542b033da87071","status":"active","name":"BDNF microinjection","description":"Direct injection of BDNF into a targeted brain region.","types":["experimental intervention"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_ca40acd8c7c25d8fac542b033da87071"},{"public_id":"co_fb17e477651e7fdd2b6c683416ddfbd0","status":"active","name":"rostral ventromedial medulla","description":"A brainstem relay region between the periaqueductal gray and the spinal cord.","types":["brain region"],"aliases":["RVM"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_fb17e477651e7fdd2b6c683416ddfbd0"}],"external_ids":{"DOI":"10.1523/JNEUROSCI.3686-05.2006","ArXiv":null,"PubMed":16399679,"PubMedCentral":"PMC6674294","MAG":2131110619,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://www.jneurosci.org/content/jneuro/26/1/126.full.pdf","landing_url":"https://www.semanticscholar.org/paper/de1113dc47a1628cc21ab985d471240bfe2b4f9a","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":"CCBYNCSA","status":"HYBRID","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":636224,"paper_uid":"4a605b54-d9f3-4958-b595-21bdca3eda24","canonical_identity":{"paper_id":636224,"paper_uid":"4a605b54-d9f3-4958-b595-21bdca3eda24","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/14558765"}