Gene Symbol: pain
Description: painless
Alias: CG15860, CT31987, Dmel\CG15860, EP2251, Pain, painless, CG15860-PA, CG15860-PB, CG15860-PC, pain-PA, pain-PB, pain-PC
Species: fruit fly
Products:     pain

Top Publications

  1. Wang K, Guo Y, Wang F, Wang Z. Drosophila TRPA channel painless inhibits male-male courtship behavior through modulating olfactory sensation. PLoS ONE. 2011;6:e25890 pubmed publisher
    The Drosophila melanogaster TRPA family member painless, expressed in a subset of multidendritic neurons embeding in the larval epidermis, is necessary for larval nociception of noxious heat or mechanical stimuli...
  2. Oswald M, Rymarczyk B, Chatters A, Sweeney S. A novel thermosensitive escape behavior in Drosophila larvae. Fly (Austin). 2011;5:304-6 pubmed publisher
    ..Larvae defective for the painless TRP receptor, or blocked in the function of class IV multi-dendritic sensory dendrites respond to this stimulus ..
  3. Xiang Y, Yuan Q, Vogt N, Looger L, Jan L, Jan Y. Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall. Nature. 2010;468:921-6 pubmed publisher
    ..These novel photoreceptors use phototransduction machinery distinct from other photoreceptors in Drosophila and enable larvae to sense light exposure over their entire bodies and move out of danger. ..
  4. Kim S, Lee Y, Akitake B, Woodward O, Guggino W, Montell C. Drosophila TRPA1 channel mediates chemical avoidance in gustatory receptor neurons. Proc Natl Acad Sci U S A. 2010;107:8440-5 pubmed publisher
    ..Given that mammalian TRPA1 is required for responding to noxious chemicals, many of which cause pain and injury, our analysis underscores the evolutionarily conserved role for TRPA1 channels in chemical avoidance.
  5. Rosenzweig M, Kang K, Garrity P. Distinct TRP channels are required for warm and cool avoidance in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2008;105:14668-73 pubmed publisher
    ..Conversely, dTRPA1 is essential for warm avoidance, but not cool avoidance. Taken together, these data demonstrate that warm and cool avoidance in the Drosophila larva involves distinct TRP channels and circuits. ..
  6. Tracey W, Wilson R, Laurent G, Benzer S. painless, a Drosophila gene essential for nociception. Cell. 2003;113:261-73 pubmed
    ..In a genetic screen for mutants defective in this noxious heat response, we identified the painless gene...
  7. Hwang R, Stearns N, Tracey W. The ankyrin repeat domain of the TRPA protein painless is important for thermal nociception but not mechanical nociception. PLoS ONE. 2012;7:e30090 pubmed publisher
    The Drosophila TRPA channel Painless is required for the function of polymodal nociceptors which detect noxious heat and noxious mechanical stimuli...
  8. Sénatore S, Rami Reddy V, Semeriva M, Perrin L, Lalevee N. Response to mechanical stress is mediated by the TRPA channel painless in the Drosophila heart. PLoS Genet. 2010;6:e1001088 pubmed publisher
    ..out a genetic screen based on the dependence of cardiac activity upon mechanical constraints and identified Painless, a TRPA channel...
  9. Sakai T, Sato S, Ishimoto H, Kitamoto T. Significance of the centrally expressed TRP channel painless in Drosophila courtship memory. Learn Mem. 2012;20:34-40 pubmed publisher
    ..This is also true for the Drosophila TRP channel encoded by painless (pain)...

More Information


  1. Kim S, Coste B, Chadha A, Cook B, Patapoutian A. The role of Drosophila Piezo in mechanical nociception. Nature. 2012;483:209-12 pubmed publisher
    Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion ..
  2. Sokabe T, Tsujiuchi S, Kadowaki T, Tominaga M. Drosophila painless is a Ca2+-requiring channel activated by noxious heat. J Neurosci. 2008;28:9929-38 pubmed publisher
    ..They are primary sensors for detecting environmental temperatures. The Drosophila TRP channel Painless is believed responsible for avoidance of noxious heat because painless mutant flies display defects in heat ..
  3. Neely G, Hess A, Costigan M, Keene A, Goulas S, Langeslag M, et al. A genome-wide Drosophila screen for heat nociception identifies ?2?3 as an evolutionarily conserved pain gene. Cell. 2010;143:628-38 pubmed publisher
    Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden...
  4. Rosenzweig M, Brennan K, Tayler T, Phelps P, Patapoutian A, Garrity P. The Drosophila ortholog of vertebrate TRPA1 regulates thermotaxis. Genes Dev. 2005;19:419-24 pubmed
    ..Our data suggest that thermotaxis relies upon neurons and molecules distinct from those required for high-temperature nociception. We propose dTRPA1 may control thermotaxis by sensing environmental temperature. ..
  5. Kang K, Pulver S, Panzano V, Chang E, Griffith L, Theobald D, et al. Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature. 2010;464:597-600 pubmed publisher
    Chemical nociception, the detection of tissue-damaging chemicals, is important for animal survival and causes human pain and inflammation, but its evolutionary origins are largely unknown...
  6. Viswanath V, Story G, Peier A, Petrus M, Lee V, Hwang S, et al. Opposite thermosensor in fruitfly and mouse. Nature. 2003;423:822-3 pubmed
  7. Sakai T, Kasuya J, Kitamoto T, Aigaki T. The Drosophila TRPA channel, Painless, regulates sexual receptivity in virgin females. Genes Brain Behav. 2009;8:546-57 pubmed publisher
    Transient receptor potential (TRP) channels play crucial roles in sensory perception. Expression of the Drosophila painless (pain) gene, a homolog of the mammalian TRPA1/ANKTM1 gene, in the peripheral nervous system is required for ..
  8. Kwon Y, Shim H, Wang X, Montell C. Control of thermotactic behavior via coupling of a TRP channel to a phospholipase C signaling cascade. Nat Neurosci. 2008;11:871-3 pubmed publisher
    ..We propose that activation of TRPA1 through a signaling cascade promotes amplification of small differences in temperature and facilitates adaptation to temperatures within the comfortable range. ..
  9. Al Anzi B, Tracey W, Benzer S. Response of Drosophila to wasabi is mediated by painless, the fly homolog of mammalian TRPA1/ANKTM1. Curr Biol. 2006;16:1034-40 pubmed
    ..ITC), the pungent ingredient of wasabi, is a repellent to the insect Drosophila melanogaster, and that the painless gene, previously known to be required for larval nociception, is required for this avoidance behavior...
  10. Xu J, Sornborger A, Lee J, Shen P. Drosophila TRPA channel modulates sugar-stimulated neural excitation, avoidance and social response. Nat Neurosci. 2008;11:676-82 pubmed publisher
    ..We found that fructose potently elicited larval food-averse behaviors, and painless (pain), a transient receptor potential channel that is responsive to noxious stimuli, was required for the ..
  11. Lee Y, Lee Y, Lee J, Bang S, Hyun S, Kang J, et al. Pyrexia is a new thermal transient receptor potential channel endowing tolerance to high temperatures in Drosophila melanogaster. Nat Genet. 2005;37:305-10 pubmed
    ..From these findings, we propose that the primary in vivo role of Pyx is to protect flies from high-temperature stress. ..
  12. Johnson W, Carder J. Drosophila nociceptors mediate larval aversion to dry surface environments utilizing both the painless TRP channel and the DEG/ENaC subunit, PPK1. PLoS ONE. 2012;7:e32878 pubmed publisher
    ..Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed ..
  13. Sun Y, Liu L, Ben Shahar Y, Jacobs J, Eberl D, Welsh M. TRPA channels distinguish gravity sensing from hearing in Johnston's organ. Proc Natl Acad Sci U S A. 2009;106:13606-11 pubmed publisher
    ..genes nanchung and inactive were present in most Johnston's organ neurons, the TRPN gene nompC and the TRPA gene painless were localized to 2 subpopulations of neurons, and the TRPA gene pyrexia was expressed in cap cells that may ..
  14. Fowler M, Montell C. Drosophila TRP channels and animal behavior. Life Sci. 2013;92:394-403 pubmed publisher
    ..quot; Drosophila TRPs also function in the sensation of botanically derived insect repellents, and related TRPs in insect pests are potential targets for the development of improved repellents to combat insect-borne diseases. ..
  15. Xu S, Cang C, Liu X, Peng Y, Ye Y, Zhao Z, et al. Thermal nociception in adult Drosophila: behavioral characterization and the role of the painless gene. Genes Brain Behav. 2006;5:602-13 pubmed
    ..Abnormal nociceptive behavior of a mutant, painless, indicates that painless, a gene essential for nociception in Drosophila larvae, is also required for thermal ..
  16. Kwon Y, Kim S, Ronderos D, Lee Y, Akitake B, Woodward O, et al. Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal. Curr Biol. 2010;20:1672-8 pubmed publisher
  17. Chen Z, Wang Q, Wang Z. The amiloride-sensitive epithelial Na+ channel PPK28 is essential for drosophila gustatory water reception. J Neurosci. 2010;30:6247-52 pubmed publisher
    ..Thus, the amiloride-sensitive PPK28 channel may serve as the osmolarity sensor for gustatory water reception in the fruit fly. ..
  18. Kwon Y, Shen W, Shim H, Montell C. Fine thermotactic discrimination between the optimal and slightly cooler temperatures via a TRPV channel in chordotonal neurons. J Neurosci. 2010;30:10465-71 pubmed publisher
    ..We conclude that the decision to select the preferred over slightly cooler temperatures requires iav and is achieved by activating chordotonal neurons, which in turn induces repulsive behaviors, due to an increase in high angle turns. ..
  19. Sakai T, Watanabe K, Ohashi H, Sato S, Inami S, Shimada N, et al. Insulin-producing cells regulate the sexual receptivity through the painless TRP channel in Drosophila virgin females. PLoS ONE. 2014;9:e88175 pubmed publisher
    ..The Drosophila painless (pain) gene encodes a transient receptor potential (TRP) ion channel...
  20. Janssens K, Goethals S, Atkinson D, Ermanoska B, Fransen E, Jordanova A, et al. Human Rab7 mutation mimics features of Charcot-Marie-Tooth neuropathy type 2B in Drosophila. Neurobiol Dis. 2014;65:211-9 pubmed publisher
    ..Upon expression of mutant Rab7 in the sensory neurons, larvae present with a reduction of temperature and pain perception...
  21. Galili D, Dylla K, Lüdke A, Friedrich A, Yamagata N, Wong J, et al. Converging circuits mediate temperature and shock aversive olfactory conditioning in Drosophila. Curr Biol. 2014;24:1712-22 pubmed publisher
    ..Temperature conditioning appears to require a subset of the dopamine neurons required for electric shock conditioning. We conclude that dopamine neurons integrate different noxious signals into a general aversive reinforcement pathway. ..
  22. Montell C. Drosophila TRP channels. Pflugers Arch. 2005;451:19-28 pubmed
    ..As a result, the repertoire of biological roles attributed to Drosophila TRPs has increased considerably and is likely to lead to many additional surprises over the next few years. ..
  23. Padinjat R, Andrews S. TRP channels at a glance. J Cell Sci. 2004;117:5707-9 pubmed
  24. Terada S, Matsubara D, Onodera K, Matsuzaki M, Uemura T, Usui T. Neuronal processing of noxious thermal stimuli mediated by dendritic Ca(2+) influx in Drosophila somatosensory neurons. elife. 2016;5: pubmed publisher
    ..The precipitous fluctuation of firing rate in Class IV neurons enhanced the robust heat avoidance. We hypothesize that the Ca(2+) influx can be a key signal encoding a specific modality. ..
  25. Im S, Takle K, Jo J, Babcock D, Ma Z, Xiang Y, et al. Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila. elife. 2015;4:e10735 pubmed publisher
    b>Pain signaling in vertebrates is modulated by neuropeptides like Substance P (SP)...
  26. Wu M, Chu L, Hsiao P, Lin Y, Chi C, Liu T, et al. Optogenetic control of selective neural activity in multiple freely moving Drosophila adults. Proc Natl Acad Sci U S A. 2014;111:5367-72 pubmed publisher
    ..Given its capacity for optogenetic manipulation to transiently and independently activate/inactivate selective neurons, ALTOMS offers opportunities to systematically map brain circuits that orchestrate specific Drosophila behaviors. ..
  27. Tobin D, Bargmann C. Invertebrate nociception: behaviors, neurons and molecules. J Neurobiol. 2004;61:161-74 pubmed
    ..We begin with the neurobiology of invertebrate nociception, and then focus on molecules with conserved functions in vertebrate nociception and sensory biology. ..
  28. Aldrich B, Kasuya J, Faron M, Ishimoto H, Kitamoto T. The amnesiac gene is involved in the regulation of thermal nociception in Drosophila melanogaster. J Neurogenet. 2010;24:33-41 pubmed publisher
    ..that in the fruit fly Drosophila melanogaster, the transient receptor potential (TRP) channel encoded by the painless gene (pain) is required for detecting thermal and mechanical noxious stimuli...
  29. Neely G, Keene A, Duchek P, Chang E, Wang Q, Aksoy Y, et al. TrpA1 regulates thermal nociception in Drosophila. PLoS ONE. 2011;6:e24343 pubmed publisher
    b>Pain is a significant medical concern and represents a major unmet clinical need. The ability to perceive and react to tissue-damaging stimuli is essential in order to maintain bodily integrity in the face of environmental danger...
  30. Goodman M. Sensation is painless. Trends Neurosci. 2003;26:643-5 pubmed
    ..Thresholds for behavioral and nerve responses are elevated by mutations in the painless gene, which encodes a TRP ion channel protein...
  31. Zars T. Hot and cold in Drosophila larvae. Trends Neurosci. 2003;26:575-7 pubmed
    ..findings in Drosophila that implicate different neural substrates for low- and high-temperature responses, as well as indicating that a transient receptor potential (TRP) channel family member, painless, plays a role in these responses.
  32. Ni J, Liu L, Binari R, Hardy R, Shim H, Cavallaro A, et al. A Drosophila resource of transgenic RNAi lines for neurogenetics. Genetics. 2009;182:1089-100 pubmed publisher
  33. Sato S, Kitamoto T, Sakai T. Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications. Front Behav Neurosci. 2014;8:400 pubmed publisher
    ..b>Painless (Pain) is the Drosophila TRP channel that was initially identified as a molecular sensor responsible for ..
  34. Green E, O Callaghan E, Hansen C, Bastianello S, Bhutani S, Vanin S, et al. Drosophila circadian rhythms in seminatural environments: Summer afternoon component is not an artifact and requires TrpA1 channels. Proc Natl Acad Sci U S A. 2015;112:8702-7 pubmed publisher
    ..Studies of circadian rhythms under seminatural conditions therefore provide additional insights into the molecular basis of circadian entrainment that would otherwise be lost under the usual standard laboratory protocols. ..
  35. Oswald M, West R, Lloyd Evans E, Sweeney S. Identification of dietary alanine toxicity and trafficking dysfunction in a Drosophila model of hereditary sensory and autonomic neuropathy type 1. Hum Mol Genet. 2015;24:6899-909 pubmed publisher
    ..type 1 (HSAN1) is characterized by a loss of distal peripheral sensory and motorneuronal function, neuropathic pain and tissue necrosis...
  36. Montell C. Thermosensation: hot findings make TRPNs very cool. Curr Biol. 2003;13:R476-8 pubmed
    ..Recent work on the mouse ANKTM1 and Drosophila Painless proteins shows that members of a third TRP subfamily, TRPN, also function in thermosensation.
  37. Roos J, DiGregorio P, Yeromin A, Ohlsen K, Lioudyno M, Zhang S, et al. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol. 2005;169:435-45 pubmed
    ..We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels. ..
  38. Charlu S, Wisotsky Z, Medina A, Dahanukar A. Acid sensing by sweet and bitter taste neurons in Drosophila melanogaster. Nat Commun. 2013;4:2042 pubmed publisher
    ..The two mechanisms may allow the fly to better evaluate the risk of ingesting acidic foods and modulate its feeding decisions accordingly. ..
  39. Caterina M, Montell C. Take a TRP to beat the heat. Genes Dev. 2005;19:415-8 pubmed
  40. Lu B, Lamora A, Sun Y, Welsh M, Ben Shahar Y. ppk23-Dependent chemosensory functions contribute to courtship behavior in Drosophila melanogaster. PLoS Genet. 2012;8:e1002587 pubmed publisher
    ..Together, these data indicate that ppk23 and the cells expressing it play an important role in the peripheral sensory system that determines sexual behavior in Drosophila. ..
  41. Kraut R, Zinn K. Roundabout 2 regulates migration of sensory neurons by signaling in trans. Curr Biol. 2004;14:1319-29 pubmed
    ..The differential positioning of Cho organs between thorax and abdomen may be determined by Hox gene-mediated repression of robo2. ..
  42. Horner V, Wolfner M. Mechanical stimulation by osmotic and hydrostatic pressure activates Drosophila oocytes in vitro in a calcium-dependent manner. Dev Biol. 2008;316:100-9 pubmed publisher
    ..This will allow exploitation of Drosophila genetics to dissect molecular pathways involving Ca(2+) and the activation of development. ..
  43. Tokusumi Y, Tokusumi T, Schulz R. The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization. Biochem Biophys Res Commun. 2017;486:893-897 pubmed publisher
    ..We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite ..
  44. Kim M, Johnson W. ROS-mediated activation of Drosophila larval nociceptor neurons by UVC irradiation. BMC Neurosci. 2014;15:14 pubmed publisher
    ..Results obtained using UVC irradiation to induce ROS generation provide evidence that UVC-induced writhing behavior is mediated by endogenous production of ROS capable of activating mdIV mechanonociceptors in the larval body wall. ..
  45. Zhou Y, Cameron S, Chang W, Rao Y. Control of directional change after mechanical stimulation in Drosophila. Mol Brain. 2012;5:39 pubmed publisher
    ..This study presents an excellent starting point for further dissection of molecular and cellular mechanisms controlling directional adjustment after mechanical stimulation. ..
  46. Zhang W, Ge W, Wang Z. A toolbox for light control of Drosophila behaviors through Channelrhodopsin 2-mediated photoactivation of targeted neurons. Eur J Neurosci. 2007;26:2405-16 pubmed
    ..We showed that stimulating selectively the nociceptor of larvae expressing ChR2 elicited light-induced 'pain' response, confined freely behaving larvae in defined area and directed larva migration along a preset route...
  47. Babcock D, Shi S, Jo J, Shaw M, Gutstein H, Galko M. Hedgehog signaling regulates nociceptive sensitization. Curr Biol. 2011;21:1525-33 pubmed publisher
    ..development of analgesic tolerance to morphine (MS) or morphine antinociception in standard assays of inflammatory pain in rats and synergistically augmented and sustained morphine analgesia in assays of neuropathic pain...
  48. Jang W, Kim J, Cui S, Jo J, Lee B, Lee Y, et al. The anoctamin family channel subdued mediates thermal nociception in Drosophila. J Biol Chem. 2015;290:2521-8 pubmed publisher
    ..Therefore, our analysis suggests that Subdued channels may amplify the nociceptive neuronal firing that is initiated by thermo-TRP channels in response to thermal stimuli. ..
  49. Barbagallo B, Garrity P. Temperature sensation in Drosophila. Curr Opin Neurobiol. 2015;34:8-13 pubmed publisher
    ..key molecules mediating fly thermosensation, including the Transient Receptor Potential (TRP) channels TRPA1 and Painless, and the Gustatory Receptor Gr28b, an unanticipated thermosensory regulator normally associated with a different ..
  50. Gorczyca D, Younger S, Meltzer S, Kim S, Cheng L, Song W, et al. Identification of Ppk26, a DEG/ENaC Channel Functioning with Ppk1 in a Mutually Dependent Manner to Guide Locomotion Behavior in Drosophila. Cell Rep. 2014;9:1446-58 pubmed publisher
    ..Mutants of Piezo, a channel involved in mechanical nociception in the same neurons, did not show a defect in locomotion, suggesting distinct molecular machinery for mediating locomotor feedback and mechanical nociception. ..
  51. Ghimire S, Kim M. Defensive Behavior against Noxious Heat Stimuli Is Declined with Aging Due to Decreased Pain-Associated Gene Expression in Drosophila. Biomol Ther (Seoul). 2015;23:290-5 pubmed publisher
    ..Yet, aging-associated molecular mechanisms of pain perception remains elusive...
  52. Venkatachalam K, Luo J, Montell C. Evolutionarily conserved, multitasking TRP channels: lessons from worms and flies. Handb Exp Pharmacol. 2014;223:937-62 pubmed publisher
    ..Thus, worms and flies offer the potential to decipher roles for mammalian TRPs, which would otherwise not be suspected. ..
  53. Jeong D, Artan M, Seo K, Lee S. Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging. Front Genet. 2012;3:218 pubmed publisher
    ..In this review, we describe findings regarding how sensory nervous system components elicit physiological changes to regulate lifespan in invertebrate models, and discuss their implications in mammalian aging. ..
  54. Lacin H, Rusch J, Yeh R, Fujioka M, Wilson B, Zhu Y, et al. Genome-wide identification of Drosophila Hb9 targets reveals a pivotal role in directing the transcriptome within eight neuronal lineages, including activation of nitric oxide synthase and Fd59a/Fox-D. Dev Biol. 2014;388:117-33 pubmed publisher
    ..Together our data clarify the mechanisms through which Hb9 governs neuronal specification and differentiation and provide an initial characterization of the expression and function of Nos and fd59a in the Drosophila CNS. ..
  55. Zhang Y, Raghuwanshi R, Shen W, Montell C. Food experience-induced taste desensitization modulated by the Drosophila TRPL channel. Nat Neurosci. 2013;16:1468-76 pubmed publisher
    ..We propose that dynamic regulation of taste receptors by ubiquitin-mediated protein degradation comprises an important molecular mechanism that allows an animal to alter its taste behavior in response to a changing food environment. ..
  56. Ohyama T, Jovanic T, Denisov G, Dang T, Hoffmann D, Kerr R, et al. High-throughput analysis of stimulus-evoked behaviors in Drosophila larva reveals multiple modality-specific escape strategies. PLoS ONE. 2013;8:e71706 pubmed publisher
    ..More generally, our system and the detailed description of wild type reactions to somatosensory stimuli provide a basis for systematic identification of neurons and genes underlying these behaviors. ..