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Papers of the Week

Papers: 1 Feb 2020 - 7 Feb 2020

Animal Studies

2020 03 11

J Neurosci



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


Tewari D, Cook AD, Lee M-C, Christensen AD, Croxford A, Becher B, Poole D, Rajasekhar P, Bunnett N, Smith JE, Hamilton JA, McMahon SB
J Neurosci. 2020 03 11; 40(11):2189-2199.
PMID: 32019828.


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.The interaction of the immune system and the nervous system is known to play an important role in the development and maintenance of chronic pain disorders. Elucidating the mechanisms of these interactions is an important step towards understanding, and therefore treating, chronic pain disorders. This study provides evidence for a two-way cross talk between macrophages and nociceptors in the peripheral nervous system which may contribute to the sensitization of nociceptors by cytokines in pain development.