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In this study, we have employed a system of experiments assessing the impact of inflammatory conditioned media derived from activated immune cells on the excitability and activity of DRG neurons and how this relates to subsequent growth responses of these cells. 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\u2010promoting effects of inflammatory media. 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. Importantly, the same pharmacological blockade in\u00a0vivo abolished pain responses in a mouse model of multiple sclerosis. 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 multiple sclerosis.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16292-fig-0009-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16292","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T23:11:27Z","timestamp":1735254687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Plasticity of Mouse Dorsal Root Ganglion Neurons by Innate Immune Activation Is Influenced by Electrophysiological Activity"],"prefix":"10.1111","volume":"169","author":[{"given":"Timothy N.","family":"Friedman","sequence":"first","affiliation":[{"name":"Neuroscience and Mental Health Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn M.","family":"Lamothe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aislinn D.","family":"Maguire","sequence":"additional","affiliation":[{"name":"Neuroscience 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