{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:18Z","timestamp":1792789518100,"version":"4.5.0"},"reference-count":104,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["1R21DA039621\u201301"],"award-info":[{"award-number":["1R21DA039621\u201301"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI- 0400776"],"award-info":[{"award-number":["DBI- 0400776"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-1726368"],"award-info":[{"award-number":["DBI-1726368"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R21EB023104\u201302"],"award-info":[{"award-number":["R21EB023104\u201302"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Air Force Medical Service (AFMSA)","award":["FA8650-17-2-6836"],"award-info":[{"award-number":["FA8650-17-2-6836"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the molecular expression profiles of mRNAs in neurons, glia and infiltrating immune cells. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Previously, we have shown that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg\/kg) reduces inflammation of the sciatic nerve and relieves pain-like behavior for up to 6 days. Here, we use this targeted therapy to explore the impact on mRNA expression changes in both pain and pain-relieved states. Sciatic nerve tissue recovered from CCI animals is used to evaluate the mRNA expression profiles utilizing quantitative PCR. We observe mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine expression. Furthermore, genes associated with adhesion of macrophages, as well as changes in the neuronal and glial mRNAs are observed. Moreover, genes associated with neuropathic pain including Maob, Grin2b\/NMDAR2b, TrpV3, IL-6, Cacna1b\/Cav2.2, Itgam\/Cd11b, Scn9a\/Nav1.7, and Tac1 were all found to respond to the celecoxib loaded nanoemulsion during pain relief as compared to those animals that received drug-free vehicle. These results demonstrate that by targeting macrophage production of PGE2 at the site of injury, pain relief includes partial reversal of the gene expression profiles associated with chronic pain.<\/jats:p>","DOI":"10.3390\/ijms20215269","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T03:20:36Z","timestamp":1571973636000},"page":"5269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages"],"prefix":"10.3390","volume":"20","author":[{"given":"Andrea","family":"Stevens","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Bayer School of Natural and Environmental Sciences, Duquesne University, Pittsburgh, PA 15282, USA"},{"name":"Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA"},{"name":"Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Bertovich","sequence":"additional","affiliation":[{"name":"Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA"},{"name":"Washington and Jefferson College, Washington, PA 19610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Janjic","sequence":"additional","affiliation":[{"name":"Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA"},{"name":"Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-3676","authenticated-orcid":false,"given":"John","family":"Pollock","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bayer School of Natural and Environmental Sciences, Duquesne University, Pittsburgh, PA 15282, USA"},{"name":"Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.jpain.2012.03.009","article-title":"The economic costs of pain in the United States","volume":"13","author":"Gaskin","year":"2012","journal-title":"J. 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