{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:16:54Z","timestamp":1774343814743,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic nonspecific low back pain (CNLBP) is a prevalent global health issue. Previous studies have demonstrated comorbidity between hyperalgesia and mood disorders in nerve growth factor (NGF)\u2010induced CNLBP rat models. The Wnt\/\u03b2\u2010catenin signalling pathway plays a pivotal role in chronic pain pathogenesis by modulating glial cell activation and synaptic plasticity. However, the mechanism of this pathway underlying CNLBP and related emotional disorders remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mechanical and thermal hypersensitivity were measured via Von Frey and hot\/cold plate tests, while anxiety\u2010like and depression\u2010like behaviours were evaluated through the elevated plus maze (EPM), open field (OFT), and forced swim tests (FST). Additionally, electrophysiology, immunofluorescence, and western blot were employed to investigate the underlying mechanisms in CNLBP model rats. Furthermore, the effects of intrathecal IWR\u20101 (a Wnt\/\u03b2\u2010catenin signalling pathway inhibitor) on CNLBP rats were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The Wnt\/\u03b2\u2010catenin signalling pathway was activated in NGF\u2010CNLBP model rats. Three consecutive days of intrathecal IWR\u20101 administration significantly alleviated mechanical hyperalgesia (\u2265\u200910\u2009days), cold hyperalgesia (\u2265\u20099\u2009days), and heat hyperalgesia (\u2265\u20094\u2009days), while improving anxiety\u2010like behaviours in CNLBP rats. IWR\u20101 reduced ACC pyramidal neuron excitability and excitatory transmission and suppressed glial activation in the spinal dorsal horn in CNLBP rats. Notably, IWR\u20101 selectively downregulated spinal NR1 (N\u2010methyl\u2010D\u2010aspartate receptor subunit 1) protein expression level in CNLBP rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibiting spinal Wnt\/\u03b2\u2010catenin signal pathway attenuates CNLBP\u2010related hyperalgesia and anxiety and modulates ACC neuronal excitability, glial activity, and NR1 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Modulating the spinal Wnt\/\u03b2\u2010catenin signalling pathway may be pivotal for elucidating the mechanisms underlying hyperalgesia and anxiety\u2010like behaviour in chronic nonspecific low back pain (CNLBP).<\/jats:p>\n                  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