{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:46:28Z","timestamp":1792586788340,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuropathic pain (NP), a debilitating complication of chronic diseases such as diabetes and cancer, remains inadequately managed by current therapies; approximately 30% of patients are unresponsive to monotherapy. This study investigates the effects and potential mechanisms of veratramine, a natural compound, in a rodent model of chronic constriction injury (CCI)\u2013induced neuropathic pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NP was induced via CCI in rodents. Veratramine's effects were assessed through behavioural tests (mechanical withdrawal threshold [MWT] and thermal withdrawal latency [TWL]). Apoptosis and inflammation in the sciatic nerve were analysed. Western blotting and immunofluorescence evaluated phosphorylation of NF\u2010\u03baB, I\u03baB, p38 MAPK, and spinal glial activation. Transcriptome profiling identified key pathways, validated using the PI3K\/Akt agonist 740 Y\u2010P.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Veratramine significantly increased MWT and TWL, alleviating mechanical and thermal hypersensitivity. It reduced neuronal apoptosis and inflammatory cytokine release at injury sites. Protein analysis showed suppressed phosphorylation of NF\u2010\u03baB, I\u03baB, and p38 MAPK, alongside reduced numbers of Iba\u20101\u2010positive and GFAP\u2010positive cells in the spinal dorsal horn. Transcriptome data implicated PI3K\/Akt signalling pathway inhibition, confirmed by 740 Y\u2010P co\u2010treatment reversing veratramine's anti\u2010inflammatory and analgesic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that veratramine attenuates neuropathic pain in CCI rats, and its effects may involve inhibition of the PI3K\/Akt signalling pathway, leading to reduced neuroinflammation and apoptosis. This study supports a role for veratramine in the modulation of neuropathic pain and highlights the PI3K\/Akt pathway as a potential target for further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>The results of this study suggest that veratramine alleviates neuropathic pain in a rat model of CCI, and this effect is associated with suppression of the PI3K\/Akt signalling pathway. These findings support a role for veratramine in modulating neuroinflammation and apoptosis, and may contribute to a better understanding of the molecular mechanisms involved in neuropathic pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70383","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:04:08Z","timestamp":1791965048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Veratramine Alleviates Neuropathic Pain in Male Rats With Chronic Constriction Injury and Inhibits the\n                    <scp>PI3K<\/scp>\n                    \/Akt Pathway"],"prefix":"10.1002","volume":"30","author":[{"given":"Yaoping","family":"Yu","sequence":"first","affiliation":[{"name":"Pain Medicine Department Ningbo Rehabilitation Hospital  Ningbo Zhejiang 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