{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:50:30Z","timestamp":1767923430135,"version":"3.49.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:p>Paclitaxel is a widely used chemotherapeutic agent for treating various solid tumors. However, resulting neuropathic pain, often a lifelong side effect of paclitaxel, can limit dosing and compromise optimal treatment. The choroid plexus, located in the brain ventricles, spreads peripheral inflammatory reactions into the brain. Our study is the first to analyze the effects of paclitaxel on inflammatory alterations in the choroid plexus. We hypothesized that the choroid plexus could respond <jats:italic>directly<\/jats:italic> to paclitaxel and simultaneously be <jats:italic>indirectly<\/jats:italic> altered via circulating damage-associated molecular patterns (DAMPs) produced by paclitaxel application. Using immunohistochemical and Western blot analysis, we examined the levels of toll-like receptor 9 (TLR9) and formyl peptide receptor 2 (FPR2), along with the pro-inflammatory cytokines interleukin 6 (IL6) and tumor necrosis factor \u03b1 (TNF\u03b1) in choroid plexus epithelial cells of male Wistar rats following paclitaxel treatment. Moreover, we utilized an <jats:italic>in vitro<\/jats:italic> model of choroid plexus epithelial cells, the Z310 cells, to investigate the changes in these cells in response to paclitaxel and DAMPs (CpG ODN). Our results demonstrate that paclitaxel increases TLR9 and FPR2 levels in the choroid plexus while inducing IL6 and TNF\u03b1 upregulation in both acute and chronic manners. <jats:italic>In vitro<\/jats:italic> experiments further revealed that paclitaxel <jats:italic>directly<\/jats:italic> interacts with epithelial cells of the choroid plexus, leading to increased levels of TLR9, FPR2, IL6, and TNF\u03b1. Additionally, treatment of cells with CpG ODN, an agonist of TLR9, elicited upregulation of IL6 and TNF\u03b1. Our findings determined that paclitaxel influences the choroid plexus through both <jats:italic>direct<\/jats:italic> and <jats:italic>indirect<\/jats:italic> mechanisms, resulting in inflammatory profile alterations. Given the pivotal role of the choroid plexus in brain homeostasis, a compromised choroid plexus following chemotherapy may facilitate the spread of peripheral inflammation into the brain, consequently exacerbating the development of neuropathic pain.<\/jats:p>","DOI":"10.3389\/fpain.2024.1488369","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:24:55Z","timestamp":1732515895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Paclitaxel triggers molecular and cellular changes in the choroid 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