A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene

G. Gregory Neely; Andreas Hess; Michael Costigan; Alex C Keene; Spyros Goulas; Michiel Langeslag; Robert S Griffin; Inna Belfer; Feng Dai; Shad B Smith; Luda Diatchenko; Vaijayanti Gupta; Cui-ping Xia; Sabina Amann; Silke Kreitz; Cornelia Heindl-Erdmann; Susanne Wolz; Cindy V Ly; Suchir Arora; Rinku Sarangi; Debasis Dan; Maria Novatchkova; Mark Rosenzweig; Dustin G Gibson; Darwin Truong; Daniel Schramek; Tamara Zoranovic; Shane J.F Cronin; Belinda Angjeli; Kay Brune; Georg Dietzl; William Maixner; Arabella Meixner; Winston Thomas; J. Andrew Pospisilik; Mattias Alenius; Michaela Kress; Sai Subramaniam; Paul A Garrity; Hugo J Bellen; Clifford J Woolf; Josef M Penninger

doi:10.1016/j.cell.2010.09.047

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A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene

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A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene

G. Gregory Neely, Andreas Hess, Michael Costigan, Alex C Keene, Spyros Goulas, Michiel Langeslag, Robert S Griffin, Inna Belfer, Feng Dai, Shad B Smith, …

Cell (Cambridge), Vol.143(4), pp.628-638

11/12/2010

DOI: https://doi.org/10.1016/j.cell.2010.09.047

PMID: 21074052

Abstract

Drosophila

RNAi

α2δ3 mutant mice

Temperature

Neural Stimulation

Sensory Physiology

Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj orthologCACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.

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Title: A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene; A genome-wide Drosophila pain screen identifies alpha2delta3 as an evolutionarily conserved pain gene
Creators: G. Gregory Neely - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Andreas Hess - Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany
Michael Costigan - Program in Neurobiology, Children's Hospital Boston and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Alex C Keene - Biology Department, New York University, 100 Washington Square East, New York, NY 10003, USA
Spyros Goulas - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Michiel Langeslag - Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria
Robert S Griffin - Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
Inna Belfer - Molecular Epidemiology of Pain Program, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA
Feng Dai - Molecular Epidemiology of Pain Program, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA
Shad B Smith - Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Luda Diatchenko - Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Vaijayanti Gupta - Strand Life Sciences Pvt. Ltd., 237 C V Raman Avenue, Rajmahal Vilas, Bangalore, India
Cui-ping Xia - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Sabina Amann - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Silke Kreitz - Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany
Cornelia Heindl-Erdmann - Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany
Susanne Wolz - Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany
Cindy V Ly - Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
Suchir Arora - Strand Life Sciences Pvt. Ltd., 237 C V Raman Avenue, Rajmahal Vilas, Bangalore, India
Rinku Sarangi - Strand Life Sciences Pvt. Ltd., 237 C V Raman Avenue, Rajmahal Vilas, Bangalore, India
Debasis Dan - Strand Life Sciences Pvt. Ltd., 237 C V Raman Avenue, Rajmahal Vilas, Bangalore, India
Maria Novatchkova - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Mark Rosenzweig - National Center for Behavioral Genomics, Department of Biology, Brandeis University, Waltham, MA 02458, USA
Dustin G Gibson - Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Darwin Truong - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Daniel Schramek - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Tamara Zoranovic - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Shane J.F Cronin - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Belinda Angjeli - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Kay Brune - Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany
Georg Dietzl - Howard Hughes Medical Institute, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA
William Maixner - Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Arabella Meixner - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Winston Thomas - Deltagen, Inc., 1900 South Norfolk Street, Suite 105, San Mateo, CA 94403, USA
J. Andrew Pospisilik - Max Planck Institute for Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany
Mattias Alenius - Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, SE-581 85, Sweden
Michaela Kress - Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria
Sai Subramaniam - Strand Life Sciences Pvt. Ltd., 237 C V Raman Avenue, Rajmahal Vilas, Bangalore, India
Paul A Garrity - National Center for Behavioral Genomics, Department of Biology, Brandeis University, Waltham, MA 02458, USA
Hugo J Bellen - HHMI, Department of Molecular and Human Genetics, Department of Neuroscience and Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
Clifford J Woolf - Program in Neurobiology, Children's Hospital Boston and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Josef M Penninger - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria
Publication Details: Cell (Cambridge), Vol.143(4), pp.628-638
Publisher: Elsevier Inc
Identifiers: 9923979689501921
Academic Unit: Department of Biology; Benjamin and Mae Volen National Center for Complex Systems; Interdepartmental Program in Neuroscience
Language: English
Resource Type: Journal article

A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene

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