Diosmetin Attenuates Painful Symptoms Caused by Antineoplastics Paclitaxel and Anastrozole in Mice

Cancer patients often experience painful symptoms as an adverse effect resulting from various factors, including antineoplastic therapy. Paclitaxel is a chemotherapeutic agent used to treat solid tumours and, unfortunately, causes acute and chronic peripheral neuropathic pain in patients. Anastrozole is an antineoplastic used to treat hormone receptor-positive breast cancer and causes musculoskeletal pain symptoms. The therapies used to control these pain symptoms have limited efficacy and cause adverse effects, highlighting the importance of finding new treatments. Diosmetin is a flavonoid that has shown efficacy in neuropathic, nociplastic, and inflammatory pain models. Therefore, we verified the antinociceptive effects of diosmetin on nociceptive parameters induced by paclitaxel and anastrozole. We investigated the effects of diosmetin (0.015, 0.15 and 1.5 mg/kg; oral route (p.o.)) on nociceptive parameters (mechanical and cold allodynia and pain affective‑motivational behaviour) induced by a single and repeated paclitaxel (1 mg/kg, intraperitoneal (i.p.)) administrations, as well as on the pain-like symptoms (mechanical allodynia, muscle strength, and pain affective‑motivational behaviour) of a single administration of anastrozole (0.2 mg/kg, p.o.) and the combination of both antineoplastics in mice. Diosmetin reduced the nociceptive parameters induced by paclitaxel and anastrozole. In addition, we observed that anastrozole exacerbated the mechanical allodynia induced by paclitaxel, an effect that was also reversed by diosmetin. These results suggest that diosmetin may be an effective therapeutic alternative for the treatment of painful symptoms caused by antineoplastic drugs, such as paclitaxel and anastrozole.