Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain
AuthorNencini, S; Ringuet, M; Kim, D-H; Chen, Y-J; Greenhill, C; Ivanusic, JJ
Source TitleMolecular Pain
PublisherSAGE PUBLICATIONS INC
University of Melbourne Author/sIvanusic, Jason
AffiliationAnatomy and Neuroscience
Document TypeJournal Article
CitationsNencini, S., Ringuet, M., Kim, D. -H., Chen, Y. -J., Greenhill, C. & Ivanusic, J. J. (2017). Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain. MOLECULAR PAIN, 13, https://doi.org/10.1177/1744806917697011.
Access StatusOpen Access
Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease.
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