Plasticity of mouse dorsal root ganglion neurons by innate immune activation is influenced by electrophysiological activity

Abstract

Abstract Background. The intricate interplay between inflammation, its effects on neuronal excitability, and the ensuing plasticity of dorsal root ganglion (DRG) sensory neurons remains to be fully explored. In this study, we have investigated the impact of inflammatory conditioned media on the excitability and activity of DRG neurons and how this relates to subsequent growth responses of these cells. Findings. We show here that an early phase of increased neuronal activity in response to inflammatory conditioned media is critical for the engagement of plastic processes, and that neuronal excitability profiles are linked through time to the structural phenotype of individual neurons. Pharmacological blockade of neuronal activity was able to abolish the growth promoting effects of inflammatory media. Our findings also demonstrate a sex specificity of these responses. Conclusions. Our results suggest that targeting the activity of DRG neurons may provide a novel therapeutic avenue to manipulate their growth status and potential for plasticity in response to inflammation. While further studies are needed to fully elucidate the underlying mechanisms of the relationship between neural activity and growth status, a more complete understanding of this relationship may ultimately lead to the development of new treatments for neuropathic pain in disorders associated with heightened immune responses such as rheumatoid arthritis and MS.