ArticlePLoS genetics2012
Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Injury alters sensory, motor, and integrative elements underlying operant conditioning in the medicinal leech.PloS one · 2025Article
- Vitamin B5 is a context-dependent dietary regulator of nociception.G3 (Bethesda, Md.) · 2024Article
- Characterization of plasma metabolites and proteins in patients with herpetic neuralgia and development of machine learning predictive models based on metabolomic profiling.Frontiers in molecular neuroscience · 2022Article
- PeripheralPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Nerve injury drives a heightened state of vigilance and neuropathic sensitization inScience advances · 2019Article
- BMP signaling downstream of the Highwire E3 ligase sensitizes nociceptors.PLoS genetics · 2018Article
- Car8 dorsal root ganglion expression and genetic regulation of analgesic responses are associated with a cis-eQTL in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
- The TrkA receptor mediates experimental thermal hyperalgesia produced by nerve growth factor: Modulation by the p75 neurotrophin receptor.Neuroscience · 2017Article
- Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model.Frontiers in molecular neuroscience · 2017Article
- The TRP Channels Pkd2, NompC, and Trpm Act in Cold-Sensing Neurons to Mediate Unique Aversive Behaviors to Noxious Cold in Drosophila.Current biology : CB · 2016Article
- Phosphoinositide regulation of TRPV1 revisited.Pflugers Archiv : European journal of physiology · 2015Review
- Review
- RNAi screening in Drosophila cells and in vivo.Methods (San Diego, Calif.) · 2014Review
- Article
- Article
- Nature and nurture of human pain.Scientifica · 2013Review
Corrections and comments
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Authors and funding
29 authors at 15 institutions in 7 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.