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Among the chemotherapeutic agents widely used clinically, cisplatin is associated with the development of painful and non-painful peripheral neuropathy symptoms, compromising patient treatment continuity. Preclinical studies have indicated that the transient receptor potential vanilloid 1 (TRPV1) ion channels play a crucial role in chemotherapy-induced neuropathic pain. Currently, only duloxetine is recommended for treating chemotherapy-induced peripheral neuropathy, highlighting the urgent need for novel therapies. Natural products such as diosmetin have shown promising pharmacological potential. Here, we evaluated the effects of diosmetin in a mouse model of cisplatin-induced neuropathic pain (0.23\u00a0mg\/kg, intraperitoneal). Nociceptive parameters included mechanical allodynia, affective-motivational behaviour, heat hyperalgesia, and muscle strength loss, along with hepatic [aspartate aminotransferase (AST), alanine aminotransferase (ALT)] and renal (urea and creatinine) biomarkers. Diosmetin (0.015, 0.15, and 1.5\u00a0mg\/kg) administered orally by gavage (p.o.) resulted in antinociceptive effects, reduced mechanical allodynia, and decreased affective motivational behaviours in mice. Diosmetin (0.15\u00a0mg\/kg) also reduced cisplatin-induced heat hyperalgesia and muscle strength loss, showing an efficacy comparable to that of duloxetine (30\u00a0mg\/kg, p.o., positive control) and SB-366791 (1\u00a0mg\/kg p.o., TRPV1 channel antagonist). Additionally, prior desensitisation of TRPV1-positive fibres with subcutaneous resiniferatoxin (RTX) prevents the development of mechanical allodynia and thermal hyperalgesia. Diosmetin (0.15\u00a0mg\/kg) did not alter hepatic or renal biomarkers. Diosmetin has therapeutic potential for treating pain in patients with neuropathy, and the TRPV1 channel plays a crucial role in cisplatin-induced peripheral neuropathy.<\/jats:p>","DOI":"10.1007\/s12035-026-05785-0","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:33:58Z","timestamp":1774373638000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diosmetin as an Effective Treatment for Cisplatin-Induced Neuropathic Pain in Mice which does not Cause Hepatic or Renal Biomarker Alterations"],"prefix":"10.1007","volume":"63","author":[{"given":"Patrick Tuzi","family":"Serafini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Felipe","family":"Atuati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Marchesan","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"5785_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/CAAC.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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