Evidence map›Paper›PMID 17179954›Full record

ArticleBritish journal of pharmacology2007

Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation.

S Asfaha, N Cenac, S Houle, C Altier, M D Papez, C Nguyen, M Steinhoff, K Chapman, G W Zamponi, N Vergnolle

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 9% 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

60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Efficacy of platelet-rich plasma in the treatment of hemiplegic shoulder pain.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021
    Trial
  4. Trial
  5. The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2015
    Trial
  6. Cathepsin S elicits itch and signals via protease-activated receptors.The Journal of investigative dermatology · 2010
    Trial
  7. Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026
    Review
  8. Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Protease Activated Receptors and Arthritis.International journal of molecular sciences · 2021
    Review
  17. Review
  18. Review
  19. Article
  20. Physiology and Pathophysiology of Itch.Physiological reviews · 2020
    Review
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

10 authors at 3 institutions in 3 countries.

S AsfahaMucosal Inflammation Research Group, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada.
N Cenac
S Houle
C Altier
M D Papez
C Nguyen
M Steinhoff
K Chapman
G W Zamponi
N Vergnolle
University of Calgary · CAZero to Three · USUniversity Hospital Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeProtease-activated receptor-4 (PAR(4)), the most recently discovered member of the PARs family, is activated by thrombin, trypsin and cathepsin G, but can also be selectively activated by small synthetic peptides (PAR(4)-activating peptide, PAR(4)-AP). PAR(4) is considered a potent mediator of platelet activation and inflammation. As both PAR(1) and PAR(2) have been implicated in the modulation of nociceptive mechanisms, we investigated the expression of PAR(4) in sensory neurons and the effects of its selective activation on nociception. EXPERIMENTAL APPROACH AND KEY

resultsWe demonstrated the expression of PAR(4) in sensory neurons isolated from rat dorsal root ganglia by reverse transcription-polymerase chain reaction and immunofluorescence. We found that PAR(4) colocalized with calcitonin gene-related peptide and substance P. We also showed that a selective PAR(4)-AP was able to inhibit calcium mobilization evoked by KCl and capsaicin in rat sensory neurons. Moreover, the intraplantar injection of a PAR(4)-AP significantly increased nociceptive threshold in response to thermal and mechanical noxious stimuli, while a PAR(4) inactive control peptide had no effect. The anti-nociceptive effects of the PAR(4)-AP were dose-dependent and occurred at doses below the threshold needed to cause inflammation. Finally, co-injection of the PAR(4)-AP with carrageenan significantly reduced the carrageenan-induced inflammatory hyperalgesia and allodynia, but had no effect on inflammatory parameters such as oedema and granulocyte infiltration. CONCLUSIONS AND IMPLICATIONS: Taken together, these results identified PAR(4) as a novel potential endogenous analgesic factor, which can modulate nociceptive responses in normal and inflammatory conditions.

Indexed as

AnimalsDose-Response Relationship, DrugGanglia, SpinalHot TemperatureHyperalgesiaImmunohistochemistryInflammationIn Vitro TechniquesMaleNeurons, AfferentOligopeptidesPainPain ThresholdRatsRats, WistarReceptors, Thrombinalanyl-tyrosyl-prolyl-glycyl-lysyl-phenylalanineOligopeptidesprotease-activated receptor 4Receptors, Thrombin

Identifiers

PMID17179954
PMCPMC2042908
OpenAlexW2003350056

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.