Evidence map›Paper›PMID 22928864›Full record

ArticleBritish journal of pharmacology2013

4α-phorbol 12,13-didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4.

R Alexander, A Kerby, A A Aubdool, A R Power, S Grover, C Gentry, A D Grant

Open access · greenAbstract read
In one paragraph

Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 29% 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

24 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. TRPing on Cell Swelling - TRPV4 Senses It.Frontiers in immunology · 2021
    Review
  6. Article
  7. Review
  8. TRPV4 receptor as a functional sensory molecule in bladder urothelium: Stretch-independent, tissue-specific actions and pathological implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

7 authors at 1 institution in 1 country.

R AlexanderWolfson Centre for Age-Related Diseases, King's College London, London, UK.
A Kerby
A A Aubdool
A R Power
S Grover
C Gentry
A D Grant
King's College London · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E527098/1
6 · The paper itself

Abstract

background and purposeThe Ca(2+) -permeable cation channel TRPV4 is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF) is increased during inflammation and causes mechanical hyperalgesia. 4α-phorbol 12,13-didecanoate (4αPDD) has been described as a selective TRPV4 agonist. We investigated NGF-induced hyperalgesia in TRPV4 wild-type (+/+) and knockout (-/-) mice, and the increases in [Ca(2+) ](i) produced by 4αPDD in cultured mouse dorsal root ganglia neurons following exposure to NGF. EXPERIMENTAL APPROACH: Withdrawal thresholds to heat, von Frey hairs and pressure were measured in mice before and after systemic administration of NGF. Changes in intracellular Ca(2+) concentration were measured by ratiometric imaging with Fura-2 in cultured DRG and trigeminal ganglia (TG) neurons during perfusion of TRPV4 agonists. KEY

resultsAdministration of NGF caused a significant sensitization to heat and von Frey stimuli in TRPV4 +/+ and -/- mice, but only TRPV4 +/+ mice showed sensitization to noxious pressure. 4αPDD stimulated a dose-dependent increase in [Ca(2+) ](i) in neurons from +/+ and -/- mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4 agonist GSK1016790A failed to stimulate an increase in intracellular Ca(2+) in cultured neurons. Responses to 4αPDD were unaffected by pretreatment with NGF. CONCLUSIONS AND IMPLICATIONS: TRPV4 contributes to mechanosensation in vivo, but there is little evidence for functional TRPV4 in cultured DRG and TG neurons. We conclude that 4αPDD activates these neurons independently of TRPV4, so it is not appropriate to refer to 4αPDD as a selective TRPV4 agonist.

Indexed as

AnimalsCalciumCell LineCells, CulturedFemaleGanglia, SpinalHumansHyperalgesiaMaleMiceMice, KnockoutNerve Growth FactorNeuronsPhorbol EstersTrigeminal GanglionTRPV Cation ChannelsCalciumNerve Growth Factorphorbol-12,13-didecanoatePhorbol EstersTrpv4 protein, mouseTRPV Cation Channels

Identifiers

PMID22928864
PMCPMC3579293
OpenAlexW1522365681

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.