Evidence map›Paper›PMID 26911685›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016

P2Y Receptors Sensitize Mouse and Human Colonic Nociceptors.

James R F Hockley, Michael M Tranter, Cian McGuire, George Boundouki, Vincent Cibert-Goton, Mohamed A Thaha, L Ashley Blackshaw, Gregory J Michael, Mark D Baker, Charles H Knowles and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
9.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
  2. Gut-brain communication: types of sensory nerves and mechanisms of activation.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. KAmerican journal of physiology. Gastrointestinal and liver physiology · 2023
    Article
  8. Activation of P2Y1R impedes intestinal mucosa repair during colitis.International journal of biological sciences · 2023
    Article
  9. NaJournal of neurophysiology · 2022
    Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Archiv : European journal of physiology · 2020
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. PJournal of pain research · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

James R F HockleyWingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AJ, United Kingdom, National Centre for Bowel Research and Surgical Innovation, and.
Michael M TranterNational Centre for Bowel Research and Surgical Innovation, and.
Cian McGuireNational Centre for Bowel Research and Surgical Innovation, and.
George BoundoukiWingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AJ, United Kingdom, National Centre for Bowel Research and Surgical Innovation, and.ORCID http://orcid.org/0000-0003-1020-5029
Vincent Cibert-GotonNational Centre for Bowel Research and Surgical Innovation, and.
Mohamed A ThahaNational Centre for Bowel Research and Surgical Innovation, and.
L Ashley BlackshawNational Centre for Bowel Research and Surgical Innovation, and.
Gregory J MichaelCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom, and.ORCID http://orcid.org/0000-0002-5035-3918
Mark D BakerCentre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom, and.
Charles H KnowlesNational Centre for Bowel Research and Surgical Innovation, and.
Wendy J WinchesterNeusentis (Pfizer Ltd.), Cambridge CB21 6GS, United Kingdom.
David C BulmerWingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AJ, United Kingdom, National Centre for Bowel Research and Surgical Innovation, and d.bulmer@qmul.ac.uk.ORCID http://orcid.org/0000-0002-4703-7877
Queen Mary University of London · GBPfizer (United States) · US

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council G0900907Wellcome Trust
6 · The paper itself

Abstract

Activation of visceral nociceptors by inflammatory mediators contributes to visceral hypersensitivity and abdominal pain associated with many gastrointestinal disorders. Purine and pyrimidine nucleotides (e.g., ATP and UTP) are strongly implicated in this process following their release from epithelial cells during mechanical stimulation of the gut, and from immune cells during inflammation. Actions of ATP are mediated through both ionotropic P2X receptors and metabotropic P2Y receptors. P2X receptor activation causes excitation of visceral afferents; however, the impact of P2Y receptor activation on visceral afferents innervating the gut is unclear. Here we investigate the effects of stimulating P2Y receptors in isolated mouse colonic sensory neurons, and visceral nociceptor fibers in mouse and human nerve-gut preparations. Additionally, we investigate the role of Nav1.9 in mediating murine responses. The application of UTP (P2Y2 and P2Y4 agonist) sensitized colonic sensory neurons by increasing action potential firing to current injection and depolarizing the membrane potential. The application of ADP (P2Y1, P2Y12, and P2Y13 agonist) also increased action potential firing, an effect blocked by the selective P2Y1 receptor antagonist MRS2500. UTP or ADP stimulated afferents, including mouse and human visceral nociceptors, in nerve-gut preparations. P2Y1 and P2Y2 transcripts were detected in 80% and 56% of retrogradely labeled colonic neurons, respectively. Nav1.9 transcripts colocalized in 86% of P2Y1-positive and 100% of P2Y2-positive colonic neurons, consistent with reduced afferent fiber responses to UTP and ADP in Na(v)1.9(-/-) mice. These data demonstrate that P2Y receptor activation stimulates mouse and human visceral nociceptors, highlighting P2Y-dependent mechanisms in the generation of visceral pain during gastrointestinal disease.

Indexed as

AdolescentAdultAgedAged, 80 and overAnimalsCells, CulturedColonFemaleGanglia, SpinalHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedNAV1.9 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelPurine NucleotidesPyrimidine NucleotidesReceptors, Purinergic P2YScn11a protein, mouseATPNav1.9nociceptorP2Y receptorspurinergic signalingvisceral pain

Identifiers

PMID26911685
PMCPMC4764659
OpenAlexW2340345717

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.