Granulocyte-macrophage colony stimulating factor as an indirect mediator of nociceptor activation and pain

Damini Tewari, Andrew Cook, Ming Chin Lee, Anne D. Christensen, Andrew Lewis Croxford, Burkhard Becher, Daniel P. Poole, Pradeep Rajasekhar, Nigel Bunnett, Julia E Smith, John A. Hamilton, Stephen B McMahon

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Abstract

The interaction between the immune system and the nervous system has been at the centre of multiple research studies in recent years. While 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 analysed 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 (NGF), could also modify macrophage gene transcription, providing further evidence for a bidirectional crosstalk.
Original languageEnglish
Pages (from-to)2189-2199
Number of pages11
JournalJournal of Neuroscience
Volume40
Issue number11
DOIs
Publication statusPublished - 11 Mar 2020

Cite this

Tewari, D., Cook, A., Lee, M. C., Christensen, A. D., Croxford, A. L., Becher, B., ... McMahon, S. B. (2020). Granulocyte-macrophage colony stimulating factor as an indirect mediator of nociceptor activation and pain. Journal of Neuroscience, 40(11), 2189-2199. https://doi.org/10.1523/JNEUROSCI.2268-19.2020