{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:39:01Z","timestamp":1793709541482,"version":"4.6.1"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>JOURNAL\/nrgr\/04.03\/01300535-202310000-00031\/figure1\/v\/2026-05-25T160659Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    In response to spinal surgery, neurons secrete a large amount of substance P into the epidural area. Substance P is involved in macrophage differentiation and fibrotic disease. However, the specific roles and mechanisms of substance P in epidural fibrosis remain unclear. In this study, we established a mouse model of L1\u2013L3 laminectomy and found that dorsal root ganglion neurons and the macrophages infiltrating into the wound area released sphingolipids.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    experiments revealed that type 1 macrophages secreted substance P, which promoted differentiation of type 1 macrophages towards a type 2 phenotype. High-throughput mRNA-seq analysis revealed that the sphingolipid metabolic pathway may be involved in the regulation of type 2 macrophages by substance P. Specifically, sphingomyelin synthase 2, a component of the sphingolipid metabolic pathway, promoted M2 differentiation in substance P-treated macrophages, while treating the macrophages with LY93, a sphingomyelin synthase 2 inhibitor, suppressed M2 differentiation. In addition, substance P promoted the formation of neutrophil extracellular traps, which further boosted M2 differentiation. Blocking substance P with the neurokinin receptor 1 inhibitor RP67580 decreased the number of M2 macrophages in the wound area after spinal surgery and alleviated epidural fibrosis, as evidenced by decreased fibronectin, \u03b1-smooth muscle actin, and collagen I in the scar tissue. These results demonstrated that substance P promotes M2 macrophage differentiation in epidural fibrosis via sphingomyelin synthase 2 and neutrophil extracellular traps. These findings provide a novel strategy for the treatment of epidural fibrosis.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.369120","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T02:25:33Z","timestamp":1676427933000},"page":"2252-2259","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Substance P promotes epidural fibrosis via induction of type 2 macrophages"],"prefix":"10.4103","volume":"18","author":[{"given":"Feng","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Ran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 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