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In this study, we aimed to investigate whether much higher plasma advanced glycation end products (AGEs) concentrations discriminate between diabetes\u2010affected individuals with pain and those without pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We administered exogenous AGEs intravenously to C57BL\/6J wild\u2010type mice and assessed nociceptive behaviours, as well as anxiety\u2010 and depression\u2010like behaviours. To explore the further mechanism, we knocked out the protein tyrosine phosphatase 1B (PTP1B) in the spinal dorsal horn by injecting the AAV viral construct encoding short\u2010hairpin RNA (shRNA). Electrophysiological recordings were used to assay the N\u2010methyl\u2010D\u2010aspartate receptor (NMDAR) function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that elevated plasma AGEs levels led to significant hyperalgesia, which was alleviated by the specific knockout of PTP1B in the spinal dorsal horn. However, this knockout did not ameliorate AGEs\u2010induced anxiety\u2010 and depression\u2010like behaviours. Electrophysiological recordings revealed that AGEs enhanced NMDAR\u2010mediated excitatory postsynaptic currents (eEPSCs) in spinal cord slices, an effect attenuated by PTP1B inhibition. Biochemical analyses showed that AGEs decreased phosphorylation at the Tyr529 site of Src kinase and increased phosphorylation at the Tyr1472 site of the NMDAR subunit 2B (GluN2B); these changes were reversed by PTP1B knockdown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that elevated plasma AGEs contribute to hyperalgesia through a PTP1B\u2010dependent mechanism involving Src\/NMDAR signalling in the spinal dorsal horn. Targeting the AGEs\u2010PTP1B\u2010NMDAR pathway may offer new therapeutic strategies for managing DNP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70141","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T10:30:04Z","timestamp":1758191404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Advanced glycation end products mediated diabetic neuropathic pain via activation protein tyrosine phosphatase\n                    <scp>1B<\/scp>\n                    in the spinal cord dorsal horn"],"prefix":"10.1111","volume":"43","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Ningxia Medical University  Yinchuan Ningxia People's Republic of China"},{"name":"Department of Pharmacy Gansu Provincial Hospital  Lanzhou Gansu People's Republic of 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