Evidence map›Paper›PMID 15764707›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2005

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1.

Ning Zhang, Saadet Inan, Sadeet Inan, Alan Cowan, Ronghua Sun, Ji Ming Wang, Thomas J Rogers, Michael Caterina, Joost J Oppenheim

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 116 papers.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed
11.2field-weighted citation impact, top 1% 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

116 citing papers in PubMed, 245 citations in OpenAlex.

  1. Trial
  2. Article
  3. Nociceptor neurons shape antiviral immunity.Journal of neuroinflammation · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Immune drivers of physiological and pathological pain.The Journal of experimental medicine · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. IMT504 Provides Analgesia by Modulating Cell Infiltrate and Inflammatory Milieu in a Chronic Pain Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021
    Article
  20. Review

56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
    Inan, Sadeet [corrected to Inan, Saadet]
5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Ning ZhangLaboratory of Molecular Immunoregulation, Intramural Research Support Program, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA.
Saadet Inan
Sadeet Inan
Alan Cowan
Ronghua Sun
Ji Ming Wang
Thomas J Rogers
Michael Caterina
Joost J Oppenheim
Johns Hopkins Medicine · USJohns Hopkins University · USNational Cancer Institute · USTemple University · US

Funding

Pilot Projects Core (PPC)P30DA013429 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI Anjali M Rajadhyaksha · 2000 to 2026
$34.6M
TRAINING PROGRAM: DRUGS OF ABUSE RELATED NEUROPEPTIDEST32DA007237 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ELLEN M UNTERWALD · 1988 to 2026
$10.6M
OPIOIDS, OPIOID RECEPTORS, AND IMMUNE COMPETENCER01DA006650 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ADLER, MARTIN W · 1991 to 2012
$5.0M
Opioid &Chemokine Receptor Interactions Relative to HIVR01DA014230 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ROGERS, THOMAS J · 2001 to 2016
$5.0M
Studies of Chemokine-Receptor Interactions with Chemokines and alarminsZ01BC009369 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI OPPENHEIM, JOOST J · 1996 to 2008
$1.8M
HIV INFECTION AND OPIOID-INDUCED IMMUNOREGULATIONR01DA016544 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ROGERS, THOMAS J · 2003 to 2007
$1.1M
The Role of Cellular Receptors Involved in Inflammation and Tumor ProgressionZ01BC010015 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, JI MING · 1996 to 2008
$944k
Consequences of receptor cross talk on inflammation and algesiaZ01BC010708 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI OPPENHEIM, JOOST J · 2006 to 2008
$463k
NIDA NIH HHS DA-06650NIDA NIH HHS DA-13429NIDA NIH HHS DA14230NIDA NIH HHS DA-16544NIDA NIH HHS P30 DA013429NIDA NIH HHS R01 DA006650NIDA NIH HHS R01 DA014230NIDA NIH HHS R01 DA016544NIDA NIH HHS T32 DA007237NIDA NIH HHS T32DA07237
6 · The paper itself

Abstract

Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca(2+) influx mediated by TRPV1. When CCR1:TRPV1/HEK293 cells were pretreated with CCL3, the sensitivity of TRPV1, as indicated by the Ca(2+) influx, was increased approximately 3-fold. RT-PCR analysis showed that a spectrum of chemokine and cytokine receptors is expressed in rat dorsal root ganglia (DRG). Immunohistochemical staining of DRG showed that CCR1 is coexpressed with TRPV1 in >85% of small-diameter neurons. CCR1 on DRG neurons was functional, as demonstrated by CCL3-induced Ca(2+) ion influx and PKC activation. Pretreatment with CCL3 enhanced the response of DRG neurons to capsaicin or anandamide. This sensitization was inhibited by pertussis toxin, U73122, or chelerythrine chloride, inhibitors of Gi-protein, phospholipase C, and protein kinase C, respectively. Intraplantar injection of mice with CCL3 decreased their hot-plate response latency. That a proinflammatory chemokine, by interacting with its receptor on small-diameter neurons, sensitizes TRPV1 reveals a previously undescribed mechanism of receptor cross-sensitization that may contribute to hyperalgesia during inflammation.

Indexed as

AnimalsArachidonic AcidsCalcium SignalingCapsaicinCell LineCells, CulturedChemokine CCL3Chemokine CCL4EndocannabinoidsGanglia, SpinalHumansHyperalgesiaInflammationInflammation MediatorsIon Channel GatingIon ChannelsanandamideArachidonic AcidsCapsaicinCCR1 protein, humanCcr1 protein, mouseCcr1 protein, ratChemokine CCL3Chemokine CCL4EndocannabinoidsInflammation MediatorsIon ChannelsMacrophage Inflammatory ProteinsPolyunsaturated AlkamidesReceptors, CCR1Receptors, ChemokineTRPV1 protein, humanTRPV Cation Channels

Identifiers

PMID15764707
PMCPMC555471
OpenAlexW2015834221

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.