{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:13:50Z","timestamp":1793294030219,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"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. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neuropathic pain (NeP) is a major complication of spinal cord disorders that is refractory to therapy and impairs quality of life. Acute neuroinflammatory responses occur after spinal cord injury (SCI), but chronic-phase microglia\/macrophage (M\/M) dynamics and their involvement in degenerative compressive myelopathy (DCM) are unclear. Brain M\/M may contribute to persistent NeP; however, comparative analyses of SCI and DCM are lacking. The aim of this study was to investigate M\/M activation and pain-related signaling dynamics in the spinal cord and brain, and their roles in chronic NeP following SCI and DCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Contusive SCI was induced in C57BL\/6N mice. Chronic compression was modeled using\n                      <jats:italic>ttw<\/jats:italic>\n                      \/\n                      <jats:italic>ttw<\/jats:italic>\n                      mice. Motor function was assessed using the Basso Mouse Locomotor Scale. Mechanical and thermal sensitivities were evaluated. M\/M activation and pain-related molecules (p-p38, p-ERK1\/2) were assessed in spinal and brain regions using immunohistochemical staining. Cytokine expression was analyzed using western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SCI mice showed early M\/M activation at the injured site with spread to the lumbar enlargement, paralleling mechanical and thermal hypersensitivity. In DCM, M\/M activation increased with compression severity, but did not extend to the lumbar enlargement. Both models showed M\/M and pain-related upregulation of molecules in the hippocampus and amygdala, and thalamic activation in acute SCI or moderate-to-severe compression. Pro-inflammatory cytokines peaked acutely in SCI and under moderate compression in DCM. Anti-inflammatory cytokine induction was limited in DCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Distinct neuroinflammatory patterns underlie chronic NeP in SCI and DCM. SCI shows M\/M activation shifting from the injured site to the lumbar enlargement and limbic brain regions, consistent with chronic below-level pain. DCM shows localized M\/M activation, but earlier hippocampal\/amygdalar involvement, consistent with chronic at-level pain. These findings suggest pathology-specific therapeutic windows for targeting M\/M-mediated neuroinflammation to prevent NeP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2026.1769004","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:48:03Z","timestamp":1769150883000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential microglial dynamics and neuroinflammation underlying neuropathic pain in the central nervous system: comparative insights from spinal cord injury and compressive myelopathy models"],"prefix":"10.3389","volume":"20","author":[{"given":"Arisa","family":"Kubota","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Honjoh","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Matsumine","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.pneurobio.2008.09.018","article-title":"Towards a theory of chronic pain","volume":"87","author":"Apkarian","year":"2009","journal-title":"Prog. 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