Metabolic reallocation in spinal cord oligodendrocytes drives chronic pain via neuronal β-amyloid production
Year: 2026
Type: dataset
Abstract: Peripheral injury reprograms metabolism in spinal cord oligodendrocytes, initiating a molecular cascade that drives chronic pain via release of the amyloid peptide Aβ42. After injury, mouse spinal oligodendrocytes downregulate myelin protein synthesis and upregulate lipid biosynthesis but reroute lipids toward neuroplastic remodeling and away from myelin maintenance. This reallocation disrupts myelin integrity and axonal function, causing neuronal accumulation of amyloid precursor protein, enhanced BACE1 expression, and Aβ42 release during a critical temporal window for the transition to pain chronicity. Blocking Aβ42 production or clearing Aβ42 within this window prevents the emergence of persistent pain. Oligodendrocyte-specific deletion of N-acylethanolamine acid amidase—a key regulator of cell metabolism and pain—prevents injury-induced Aβ42 release and chronic pain development. These findings uncover an unexpected mechanistic link between chronic pain and Alzheimer’s-like neurodegeneration and identify the NAAA→Aβ42 pathway as a target for disease-modifying intervention.
Source: Figshare
Author: Fotio, Yannick
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7159677518