@article{a172038754b744d99a3a3e6606e85e23,
title = "Granulocyte-macrophage colony stimulating factor as an indirect mediator of nociceptor activation and pain",
abstract = "The interaction between the immune system and the nervous system has been at the center of multiple research studies in recent years. Whereas the role played by cytokines as neuronal mediators is no longer contested, the mechanisms by which cytokines modulate pain processing remain to be elucidated. In this study, we have analyzed the involvement of granulocyte-macrophage colony stimulating factor (GM-CSF) in nociceptor activation in male and female mice. Previous studies have suggested GM-CSF might directly activate neurons. However, here we established the absence of a functional GM-CSF receptor in murine nociceptors, and suggest an indirect mechanism of action, via immune cells. We report that GM-CSF applied directly to magnetically purified nociceptors does not induce any transcriptional changes in nociceptive genes. In contrast, conditioned medium from GM-CSF-treated murine macrophages was able to drive nociceptor transcription. We also found that conditioned medium from nociceptors treated with the well established pain mediator, nerve growth factor, could also modify macrophage gene transcription, providing further evidence for a bidirectional crosstalk.",
keywords = "Chronic pain, GM-CSF, Neuroimmune interaction",
author = "Damini Tewari and Cook, {Andrew D.} and Lee, {Ming Chin} and Christensen, {Anne D.} and Andrew Croxford and Burkhard Becher and Daniel Poole and Pradeep Rajasekhar and Nigel Bunnett and Smith, {Julia E.} and Hamilton, {John A.} and McMahon, {Stephen B.}",
note = "Funding Information: Received Sept. 16, 2019; revised Jan. 7, 2020; accepted Jan. 14, 2020. Author contributions: D.T., A.D. Cook, J.E.S., J.A.H., and S.B.M. designed research; D.T., A.D. Cook, M.-C.L., A.D. Christensen,A.C.,B.B.,D.P.,P.R.,andN.B.performedresearch;D.T.analyzeddata;D.T.,A.D.Cook,J.A.H.,andS.B.M. wrote the paper. This work was supported by the Wellcome trust Senior Investigator Award to S.B.M., GlaxoSmith-Kline, and by Grant1043147fromtheNationalHealthandMedicalResearchCouncilofAustralia.WethankDr.FranziskaDenkfor advice on accessing publicly available RNA-seq data. Julia E. Smith is an employee of GSK. J.E.S. is an employee and shareholder of GSK. The remaining authors declare no competing financial interests. Correspondence should be addressed to Damini Tewari at damini.1.tewari@kcl.ac.uk. https://doi.org/10.1523/JNEUROSCI.2268-19.2020 Copyright {\textcopyright} 2020 the authors Funding Information: This work was supported by the Wellcome trust Senior Investigator Award to S.B.M., GlaxoSmith-Kline, and by Grant 1043147 from the National Health and Medical Research Council of Australia. We thank Dr. Franziska Denk for advice on accessing publicly available RNA-seq data. Julia E. Smith is an employee of GSK. Publisher Copyright: Copyright {\textcopyright} 2020 the authors.",
year = "2020",
month = mar,
day = "11",
doi = "10.1523/JNEUROSCI.2268-19.2020",
language = "English (US)",
volume = "40",
pages = "2189--2199",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",
}