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After injury, mouse spinal oligodendrocytes downregulate myelin protein synthesis and upregulate lipid biosynthesis\u2014but reroute lipids toward neuroplastic remodeling and away from myelin maintenance. This metabolic reallocation disrupts myelin integrity and axonal function, causing neuronal accumulation of amyloid precursor protein, enhanced expression of its processing \u03b2-secretase BACE1, and local release of A\u03b2 peptides. Blocking A\u03b2 production or clearing A\u03b2 deposits stops the transition to pain chronicity. Deleting the lysosomal lipid hydrolase NAAA in oligodendrocytes prevents both injury-induced A\u03b2 production and chronic pain development. The findings identify an unexpected mechanistic link between chronic pain and Alzheimer\u2019s-like neurodegeneration, positioning A\u03b2 as a target for therapeutic intervention.<\/jats:p>","DOI":"10.64898\/2026.01.23.701389","type":"posted-content","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T19:45:11Z","timestamp":1769370311000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic reallocation in spinal cord oligodendrocytes drives chronic pain via neuronal \u03b2-amyloid production"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5193-2009","authenticated-orcid":false,"given":"Yannick","family":"Fotio","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6193-2939","authenticated-orcid":false,"given":"Saeed","family":"Al Masri","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA, USA"},{"name":"Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2844-5816","authenticated-orcid":false,"given":"Zechuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-5848","authenticated-orcid":false,"given":"Johnny","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varvara I.","family":"Rubtsova","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3986-8344","authenticated-orcid":false,"given":"Alex","family":"Mabou Tagne","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-4213","authenticated-orcid":false,"given":"Cholsoon","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3762-2746","authenticated-orcid":false,"given":"Vivek","family":"Swarup","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-774X","authenticated-orcid":false,"given":"Daniele","family":"Piomelli","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA, USA"},{"name":"Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA"},{"name":"Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020502102794000_2026.01.23.701389v1.1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000809"},{"key":"2026020502102794000_2026.01.23.701389v1.2","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1097\/BRS.0b013e318067dce8","article-title":"Factors associated with back pain after physical injury: a survey of consecutive major trauma patients","volume":"32","year":"2007","journal-title":"Spine (Phila Pa 1976)"},{"key":"2026020502102794000_2026.01.23.701389v1.3","doi-asserted-by":"crossref","unstructured":"R. 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