Evidence map›Paper›PMID 33010954›Full record

ReviewTrends in pharmacological sciences2020

Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.

Silvia Squillace, Sarah Spiegel, Daniela Salvemini

Abstract readReview
In one paragraph

Review in Trends in pharmacological sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Metabolism of sphingolipids in a rat spinal cord stenosis model.Biochemistry and biophysics reports · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  13. Article
  14. Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024
    Review
  15. Article
  16. Article
  17. Targeting neuroinflammation in neuropathic pain and opioid use.The Journal of experimental medicine · 2023
    Article
  18. Article
  19. Article
  20. 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

3 authors.

Silvia SquillaceDepartment of Pharmacology and Physiology and the Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Sarah SpiegelDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Daniela SalveminiDepartment of Pharmacology and Physiology and the Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. Electronic address: daniela.salvemini@health.slu.edu.

Funding

SPHINGOSINE AS A MODULATOR OF CELLULAR PROLIFERATIONR01GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1990 to 2023
$3.8M
Role of opioid-induced S1P/S1PR1 axis activation in neuroinflammatory reponsesR01DA043543 · NIDA · SAINT LOUIS UNIVERSITY · PI SALVEMINI, DANIELA, VANDERAH, TODD W · 2018 to 2020
$1.7M
Role of peroxynitrite in morphine hyperalgesia and toleranceR01DA024074 · NIDA · SAINT LOUIS UNIVERSITY · PI SALVEMINI, DANIELA · 2008 to 2012
$1.7M
Targeting the relief of chronic pain with orally active peroxynitrite decompositiRC1AR058231 · NIAMS · SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE · PI NEUMANN, WILLIAM, SALVEMINI, DANIELA · 2009 to 2010
$974k
Role of ceramide in morphine hyperalgesia and toleranceR21DA023056 · NIDA · SAINT LOUIS UNIVERSITY · PI SALVEMINI, DANIELA · 2008 to 2009
$392k
NIAMS NIH HHS RC1 AR058231NIDA NIH HHS R01 DA024074NIDA NIH HHS R01 DA043543NIDA NIH HHS R21 DA023056NIGMS NIH HHS R01 GM043880
6 · The paper itself

Abstract

Chronic pain is a life-altering condition affecting millions of people. Current treatments are inadequate and prolonged therapies come with severe side effects, especially dependence and addiction to opiates. Identification of non-narcotic analgesics is of paramount importance. Preclinical and clinical studies suggest that sphingolipid metabolism alterations contribute to neuropathic pain development. Functional sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) antagonists, such as FTY720/fingolimod, used clinically for non-pain conditions, are emerging as non-narcotic analgesics, supporting the repurposing of fingolimod for chronic pain treatment and energizing drug discovery focused on S1P signaling. Here, we summarize the role of S1P in pain to highlight the potential of targeting the S1P axis towards development of non-narcotic therapeutics, which, in turn, will hopefully help lessen misuse of opioid pain medications and address the ongoing opioid epidemic.

Indexed as

Analgesics, Non-NarcoticAnimalsChronic PainHumansLysophospholipidsMolecular Targeted TherapyPain ManagementSignal TransductionSphingosineSphingosine-1-Phosphate ReceptorsAnalgesics, Non-NarcoticLysophospholipidsSphingosinesphingosine 1-phosphateSphingosine-1-Phosphate Receptorsneuroinflammationneuropathic painnon-narcotic treatmentsS1P receptorssphingosine-1-phosphate (S1P)

Identifiers

PMID33010954
PMCPMC8491165

What OpenQuestion holds

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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.