Evidence map›Paper›PMID 26283908›Full record

ArticleFrontiers in molecular neuroscience2015

Sphingosine kinase 2-deficiency mediated changes in spinal pain processing.

Jastrow Canlas, Phillip Holt, Alexander Carroll, Shane Rix, Paul Ryan, Lorena Davies, Dusan Matusica, Stuart M Pitson, Claire F Jessup, Ian L Gibbins and 1 more

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

Article in Frontiers in molecular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The Functional Role of Sphingosine Kinase 2.Frontiers in molecular biosciences · 2021
    Review
  5. Review
  6. 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

11 authors at 1 institution in 1 country.

Jastrow CanlasPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Phillip HoltPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Alexander CarrollPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Shane RixPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Paul RyanPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Lorena DaviesCentre for Cancer Biology, University of South Australia and SA Pathology Adelaide, SA, Australia.
Dusan MatusicaPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Stuart M PitsonCentre for Cancer Biology, University of South Australia and SA Pathology Adelaide, SA, Australia.
Claire F JessupPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Ian L GibbinsPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Rainer V HaberbergerPain and Pulmonary Neurobiology, Anatomy and Histology, Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
Flinders University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic pain is one of the most burdensome health issues facing the planet (as costly as diabetes and cancer combined), and in desperate need for new diagnostic targets leading to better therapies. The bioactive lipid sphingosine 1-phosphate (S1P) and its receptors have recently been shown to modulate nociceptive signaling at the level of peripheral nociceptors and central neurons. However, the exact role of S1P generating enzymes, in particular sphingosine kinase 2 (Sphk2), in nociception remains unknown. We found that both sphingosine kinases, Sphk1 and Sphk2, were expressed in spinal cord (SC) with higher levels of Sphk2 mRNA compared to Sphk1. All three Sphk2 mRNA-isoforms were present with the Sphk2.1 mRNA showing the highest relative expression. Mice deficient in Sphk2 (Sphk2(-/-)) showed in contrast to mice deficient in Sphk1 (Sphk1(-/-)) substantially lower spinal S1P levels compared to wild-type C57BL/6 mice. In the formalin model of acute peripheral inflammatory pain, Sphk2(-/-) mice showed facilitation of nociceptive transmission during the late response, whereas responses to early acute pain, and the number of c-Fos immunoreactive dorsal horn neurons were not different between Sphk2(-/-) and wild-type mice. Chronic peripheral inflammation (CPI) caused a bilateral increase in mechanical sensitivity in Sphk2(-/-) mice. Additionally, CPI increased the relative mRNA expression of P2X4 receptor, brain-derived neurotrophic factor and inducible nitric oxide synthase in the ipsilateral SC of wild-type but not Sphk2(-/-) mice. Similarly, Sphk2(-/-) mice showed in contrast to wild-type no CPI-dependent increase in areas of the dorsal horn immunoreactive for the microglia marker Iba-1 and the astrocyte marker Glial fibrillary acidic protein (GFAP). Our results suggest that the tightly regulated cell signaling enzyme Sphk2 may be a key component for facilitation of nociceptive circuits in the CNS leading to central sensitization and pain memory formation.

Indexed as

CFAdorsal hornformalinknock-out mouseRT-PCRsphingosine 1-phosphate

Identifiers

PMID26283908
PMCPMC4522551
OpenAlexW1499751748

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.