painless, a Drosophila Gene Essential for Nociception

We describe a paradigm for nociception in Drosophila. In response to the touch of a probe heated above 38 degrees C, Drosophila larvae produce a stereotypical rolling behavior, unlike the response to an unheated probe. In a genetic screen for mutants defective in this noxious heat response, we identified the painless gene. Recordings from wild-type larval nerves identified neurons that initiated strong spiking above 38 degrees C, and this activity was absent in the painless mutant. The painless mRNA encodes a protein of the transient receptor potential ion channel family. Painless is required for both thermal and mechanical nociception, but not for sensing light touch. painless is expressed in peripheral neurons that extend multiple branched dendrites beneath the larval epidermis, similar to vertebrate pain receptors. An antibody to Painless binds to localized dendritic structures that we hypothesize are involved in nociceptive signaling.

[1]  A I Basbaum,et al.  Impaired nociception and pain sensation in mice lacking the capsaicin receptor. , 2000, Science.

[2]  L. Kelly,et al.  Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene , 1992, Neuron.

[3]  K. J. Sepp,et al.  Conversion of lacZ enhancer trap lines to GAL4 lines using targeted transposition in Drosophila melanogaster. , 1999, Genetics.

[4]  John B. Hogenesch,et al.  A Heat-Sensitive TRP Channel Expressed in Keratinocytes , 2002, Science.

[5]  C. Zuker,et al.  Genetic dissection of mechanosensory transduction: Mechanoreception-defective mutations of drosophila , 1994, Neuron.

[6]  D. McKemy,et al.  Identification of a cold receptor reveals a general role for TRP channels in thermosensation , 2002, Nature.

[7]  Y. Jan,et al.  Genes regulating dendritic outgrowth, branching, and routing in Drosophila. , 1999, Genes & development.

[8]  L. Salkoff,et al.  TRPγ, a Drosophila TRP–Related Subunit, Forms a Regulated Cation Channel with TRPL , 2000, Neuron.

[9]  N. Wittenburg,et al.  Thermal avoidance in Caenorhabditis elegans: an approach to the study of nociception. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[11]  B. Trueb,et al.  An Ankyrin-like Protein with Transmembrane Domains Is Specifically Lost after Oncogenic Transformation of Human Fibroblasts* , 1999, The Journal of Biological Chemistry.

[12]  D. Julius,et al.  A capsaicin-receptor homologue with a high threshold for noxious heat , 1999, Nature.

[13]  C. Zuker,et al.  A Drosophila mechanosensory transduction channel. , 2000, Science.

[14]  V. Hartenstein Development of Drosophila larval sensory organs: spatiotemporal pattern of sensory neurones, peripheral axonal pathways and sensilla differentiation , 1988 .

[15]  A. Basbaum,et al.  The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli , 1998, Neuron.

[16]  David E. Clapham,et al.  TRPV3 is a calcium-permeable temperature-sensitive cation channel , 2002, Nature.

[17]  C. Sherrington Integrative Action of the Nervous System , 1907 .

[18]  G. Schultz,et al.  OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity , 2000, Nature Cell Biology.

[19]  Yuh Nung Jan,et al.  Tiling of the Drosophila epidermis by multidendritic sensory neurons. , 2002, Development.

[20]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[21]  G. Rubin,et al.  Systematic gain-of-function genetics in Drosophila. , 1998, Development.

[22]  K. Broadie,et al.  Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects , 1995, Neuron.

[23]  Cori Bargmann,et al.  OSM-9, A Novel Protein with Structural Similarity to Channels, Is Required for Olfaction, Mechanosensation, and Olfactory Adaptation inCaenorhabditis elegans , 1997, The Journal of Neuroscience.

[24]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[25]  Peter McIntyre,et al.  ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures , 2003, Cell.

[26]  Lei Liu,et al.  Identification and function of thermosensory neurons in Drosophila larvae , 2003, Nature Neuroscience.

[27]  W. A. Johnson,et al.  Ripped Pocket and Pickpocket, Novel Drosophila DEG/ENaC Subunits Expressed in Early Development and in Mechanosensory Neurons , 1998, The Journal of cell biology.

[28]  B. Brembs,et al.  The operant and the classical in conditioned orientation of Drosophila melanogaster at the flight simulator. , 2000, Learning & memory.

[29]  R. Meyer,et al.  Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans. , 1995, The Journal of physiology.

[30]  J Gybels,et al.  C nociceptor activity in human nerve during painful and non painful skin stimulation. , 1981, Journal of neurology, neurosurgery, and psychiatry.

[31]  H. A. Mariath Operant conditioning in Drosophila melanogaster wild-type and learning mutants with defects in the cyclic AMP metabolism , 1985 .

[32]  M. Zimmermann,et al.  Nervous outflow from the cat's foot during noxious radiant heat stimulation. , 1974, Brain research.

[33]  E. Perl,et al.  Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. , 1969, Journal of neurophysiology.

[34]  Jingchun Zhu,et al.  nompA Encodes a PNS-Specific, ZP Domain Protein Required to Connect Mechanosensory Dendrites to Sensory Structures , 2001, Neuron.

[35]  Craig Montell,et al.  A unified nomenclature for the superfamily of TRP cation channels. , 2002, Molecular cell.

[36]  Cori Bargmann,et al.  The Gα Protein ODR-3 Mediates Olfactory and Nociceptive Function and Controls Cilium Morphogenesis in C. elegans Olfactory Neurons , 1998, Neuron.

[37]  P. Anand,et al.  TRPV3 is a temperature-sensitive vanilloid receptor-like protein , 2002, Nature.

[38]  G. Rubin,et al.  Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction , 1989, Neuron.

[39]  P. Salvaterra,et al.  Characterization of Nervana, a Drosophila melanogaster Neuron‐Specific Glycoprotein Antigen Recognized by Anti‐Horseradish Peroxidase Antibodies , 1995, Journal of neurochemistry.

[40]  Cori Bargmann,et al.  Combinatorial Expression of TRPV Channel Proteins Defines Their Sensory Functions and Subcellular Localization in C. elegans Neurons , 2002, Neuron.

[41]  Gilles Laurent,et al.  Using noise signature to optimize spike-sorting and to assess neuronal classification quality , 2002, Journal of Neuroscience Methods.