Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.
The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genom...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3516557?pdf=render |
| _version_ | 1819212853949759488 |
|---|---|
| author | G Gregory Neely Shuan Rao Michael Costigan Norbert Mair Ildiko Racz Giedre Milinkeviciute Arabella Meixner Swetha Nayanala Robert S Griffin Inna Belfer Feng Dai Shad Smith Luda Diatchenko Stefano Marengo Bernhard J Haubner Maria Novatchkova Dustin Gibson William Maixner J Andrew Pospisilik Emilio Hirsch Ian Q Whishaw Andreas Zimmer Vaijayanti Gupta Junko Sasaki Yasunori Kanaho Takehiko Sasaki Michaela Kress Clifford J Woolf Josef M Penninger |
| author_facet | G Gregory Neely Shuan Rao Michael Costigan Norbert Mair Ildiko Racz Giedre Milinkeviciute Arabella Meixner Swetha Nayanala Robert S Griffin Inna Belfer Feng Dai Shad Smith Luda Diatchenko Stefano Marengo Bernhard J Haubner Maria Novatchkova Dustin Gibson William Maixner J Andrew Pospisilik Emilio Hirsch Ian Q Whishaw Andreas Zimmer Vaijayanti Gupta Junko Sasaki Yasunori Kanaho Takehiko Sasaki Michaela Kress Clifford J Woolf Josef M Penninger |
| author_sort | G Gregory Neely |
| collection | DOAJ |
| description | The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species. |
| first_indexed | 2024-12-23T06:49:34Z |
| format | Article |
| id | doaj.art-a2539791b4e849b5b1f91655caebc579 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T06:49:34Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-a2539791b4e849b5b1f91655caebc5792022-12-21T17:56:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01812e100307110.1371/journal.pgen.1003071Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.G Gregory NeelyShuan RaoMichael CostiganNorbert MairIldiko RaczGiedre MilinkeviciuteArabella MeixnerSwetha NayanalaRobert S GriffinInna BelferFeng DaiShad SmithLuda DiatchenkoStefano MarengoBernhard J HaubnerMaria NovatchkovaDustin GibsonWilliam MaixnerJ Andrew PospisilikEmilio HirschIan Q WhishawAndreas ZimmerVaijayanti GuptaJunko SasakiYasunori KanahoTakehiko SasakiMichaela KressClifford J WoolfJosef M PenningerThe ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species.http://europepmc.org/articles/PMC3516557?pdf=render |
| spellingShingle | G Gregory Neely Shuan Rao Michael Costigan Norbert Mair Ildiko Racz Giedre Milinkeviciute Arabella Meixner Swetha Nayanala Robert S Griffin Inna Belfer Feng Dai Shad Smith Luda Diatchenko Stefano Marengo Bernhard J Haubner Maria Novatchkova Dustin Gibson William Maixner J Andrew Pospisilik Emilio Hirsch Ian Q Whishaw Andreas Zimmer Vaijayanti Gupta Junko Sasaki Yasunori Kanaho Takehiko Sasaki Michaela Kress Clifford J Woolf Josef M Penninger Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. PLoS Genetics |
| title | Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. |
| title_full | Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. |
| title_fullStr | Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. |
| title_full_unstemmed | Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. |
| title_short | Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. |
| title_sort | construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception |
| url | http://europepmc.org/articles/PMC3516557?pdf=render |
| work_keys_str_mv | AT ggregoryneely constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT shuanrao constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT michaelcostigan constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT norbertmair constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT ildikoracz constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT giedremilinkeviciute constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT arabellameixner constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT swethanayanala constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT robertsgriffin constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT innabelfer constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT fengdai constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT shadsmith constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT ludadiatchenko constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT stefanomarengo constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT bernhardjhaubner constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT marianovatchkova constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT dustingibson constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT williammaixner constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT jandrewpospisilik constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT emiliohirsch constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT ianqwhishaw constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT andreaszimmer constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT vaijayantigupta constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT junkosasaki constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT yasunorikanaho constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT takehikosasaki constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT michaelakress constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT cliffordjwoolf constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception AT josefmpenninger constructionofaglobalpainsystemsnetworkhighlightsphospholipidsignalingasaregulatorofheatnociception |