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Current pre-clinical models to investigate dysfunction of sensory neurons have shown a limited clinical translation, in part, by failing to mimic the compartmentalized nociceptor anatomy that exhibits a central compartment containing the soma and a peripheral one harboring the axon endings with distinct molecular and cellular environmental composition. Thus, there is a need to validate compartmentalized preclinical neurosensory models for investigating the pathophysiology of peripheral sensory disorders and to test drug candidates. Here, we have addressed this issue and developed a microfluidic-based preclinical nociceptor model and validated it for investigating inflammatory and neuropathic peripheral disorders. We show that this model reproduces the peripheral sensitization and resolution produced by an inflammatory soup and by the chemotherapeutic drug paclitaxel. Furthermore, compartmentalized nociceptor primary cultures were amenable to co-culture with keratinocytes in the axonal compartment. Interaction of axonal endings with keratinocytes modulated neuronal responses, consistent with a crosstalk between both cell types. These findings pave the way towards translational pre-clinical sensory models for skin pathophysiological research and drug development.<\/jats:p>","DOI":"10.1177\/17448069231197102","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T08:02:11Z","timestamp":1692000131000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Compartmentalized primary cultures of dorsal root ganglion neurons to model peripheral pathophysiological conditions"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-6759","authenticated-orcid":false,"given":"Simona","family":"Giorgi","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lamberti","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Butr\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Gross-Amat","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Alarc\u00f3n-Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Rodr\u00edguez-Ca\u00f1as","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asia","family":"Fern\u00e1ndez-Carvajal","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ferrer-Montiel","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Universitas Miguel Hern\u00e1ndez, Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"bibr1-17448069231197102","volume-title":"StatPearls","author":"Koop LK","year":"2023"},{"key":"bibr2-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00048.2009"},{"key":"bibr3-17448069231197102","volume-title":"Principles of neural science","author":"Kandel ER","year":"2000","edition":"4"},{"key":"bibr4-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2018.05.002"},{"key":"bibr5-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"bibr6-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42843"},{"key":"bibr7-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.25.7.071205"},{"key":"bibr8-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-207-4:49"},{"key":"bibr9-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2006.11.009"},{"key":"bibr10-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001145"},{"key":"bibr11-17448069231197102","doi-asserted-by":"publisher","DOI":"10.1039\/b918640a"},{"key":"bibr12-17448069231197102","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.919646"},{"issue":"6","key":"bibr13-17448069231197102","first-page":"285","volume":"9","author":"Saliba J","year":"2018","journal-title":"Genes. 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