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

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

doi:10.1016/j.cell.2010.09.047

Cited by 290 publications

(329 citation statements)

References 59 publications

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“…A role for a 2 d-3 in central pain processing in mice and humans has also been elucidated, on the basis of a Drosophila screen that identified the importance of straightjacket (stj), the Drosophila homolog of a 2 d-3, in thermal nociception (Neely et al, 2010).…”

Section: A a 2 D Subunit Genes And Gene Productsmentioning

confidence: 99%

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

Zamponi¹,

Striessnig²,

Koschak³

et al. 2015

Pharmacol Rev

903

992

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Section: A a 2 D Subunit Genes And Gene Productsmentioning

confidence: 99%

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

Zamponi¹,

Striessnig²,

Koschak³

et al. 2015

Pharmacol Rev

903

992

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“…4 Mutations in a number of Transient Receptor Potential (TRP) receptors have been identified. Behavioral analysis of TRP receptor mutants and the expression patterns of the TRP proteins have helped to identify components of the underlying neurocircuitry.…”

mentioning

confidence: 99%

“…1,2 Recent descriptions of temperature responses in Drosophila have uncovered mechanisms and pathways involved in optimal temperature detection in flies 3 that appear to be shared in nociceptive perception in mammals. 4 Mutations in a number of Transient Receptor Potential (TRP) receptors have been identified. Behavioral analysis of TRP receptor mutants and the expression patterns of the TRP proteins have helped to identify components of the underlying neurocircuitry.…”

mentioning

confidence: 99%

A novel thermosensitive escape behavior in Drosophila larvae

Oswald

Rymarczyk²,

Chatters³

et al. 2011

fly

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Animals detect and respond to temperature changes in their environment. Responses can be choice based to achieve an optimum environment for physiological function, or escape reflexes as temperature reaches noxious levels. Both types of response can be observed in Drosophila.1,2 Recent descriptions of temperature responses in Drosophila have uncovered mechanisms and pathways involved in optimal temperature detection in flies 3 that appear to be shared in nociceptive perception in mammals. 4 Mutations in a number of Transient Receptor Potential (TRP) receptors have been identified. Behavioral analysis of TRP receptor mutants and the expression patterns of the TRP proteins have helped to identify components of the underlying neurocircuitry. 1,3,[5][6][7] We describe here a robust behavioral escape response from larvae to rising temperature. The behavior closely resembles previously described nocifensive responses elicited by touch with a heated probe set at 39-41°C producing a corkscrewing avoidance of the stimulus.1 A later modification of this stimulus application employed a temperature regulated thermal probe. 8 For both studies, duration and force of contact between probe and larvae is a function of the testers' judgement and dexterity. In an attempt to remove this potential operator variability, we applied a thermal stimulus to larvae by immersion in a water droplet and subsequent heating of the water to noxious levels. In practical terms, we placed a larva in 30 μl of water at room temperature on a petri dish lid. The lid was then transferred to a hotplate surface set to 70°C. Care was taken to ensure that the petri dish lid consistently came into close contact with the hotplate. As our baseline, we used a fine temperature probe (a thermocouple) to determine the rate of temperature increase in the water droplet so that we have an exact determination of the temperature of the droplet at any time-point ( fig. 1B) Keywords: nociception, nocifensive, TRP receptor, Drosophila larvae dish holding the droplet and larva to the hot plate, we recorded the time at which the larva initiated the characteristic nocifensive corkscrew roll. We use our time/temperature relationship curve to infer the temperature in the droplet of water when the escape response is activated. In our assay, the escape response in wildtype larvae was evoked at 28-29°C ( fig. 1c). We determined the escape response temperature for larvae of our lab stock of w 1118 , and two wild-type stocks, Canton-S and Oregon-R. The three wild-type stocks all responded at a temperature just above 29°C (29.3°C, 29.8°C and 29.4°C respectively). In larvae mutant for the TRP receptor painless (pain 1 ), or functionally blocked by the expression of tetanus toxin light chain 10 in the class IV da sensory neurons, the response occurred at 33-34°C ( fig. 1c). Control animals expressing inactive tetanus toxin light chain respond at 28.1°C. This suggests that the painless TRP receptor may be involved in responses to temperature around 29°C in this behavioral test.In additi...

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“…Therefore new constructs expressing small hairpin RNAs were generated to produce second generation of transgenic RNAi Drosophila stains at Harvard medical school (Table. 2). In the past several years, a number of genome-wide RNAi screens in Drosophila have been conducted to study the major signaling pathways [51], as well as many important disease models [52][53][54][55].…”

Section: In Vivo Rnai Screenmentioning

confidence: 99%

Genome-Wide RNAi Screen for the Discovery of Gene Function, Novel Therapeutical Targets and Agricultural Applications

Bai¹

2012

Functional Genomics

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

Cited by 290 publications

References 59 publications

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

A novel thermosensitive escape behavior in Drosophila larvae

Genome-Wide RNAi Screen for the Discovery of Gene Function, Novel Therapeutical Targets and Agricultural Applications

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