Atuati Samuel Felipe, Becker Gabriela, Oliveira Sara Marchesan
Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Department of Biochemistry and Molecular Biology, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Mol Neurobiol. 2025 Apr 14. doi: 10.1007/s12035-025-04939-w.
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.
癌症患者常常经历疼痛症状，这是包括抗肿瘤治疗在内的多种因素导致的不良反应。紫杉醇是一种用于治疗实体瘤的化疗药物，不幸的是，它会导致患者出现急性和慢性外周神经性疼痛。阿那曲唑是一种用于治疗激素受体阳性乳腺癌的抗肿瘤药物，会引起肌肉骨骼疼痛症状。用于控制这些疼痛症状的疗法疗效有限且会产生不良反应，这凸显了寻找新治疗方法的重要性。香叶木素是一种黄酮类化合物，已在神经性、神经病理性和炎性疼痛模型中显示出疗效。因此，我们验证了香叶木素对紫杉醇和阿那曲唑诱导的伤害性参数的镇痛作用。我们研究了香叶木素（0.015、0.15和1.5毫克/千克；口服给药）对单次和重复给予紫杉醇（1毫克/千克，腹腔注射）诱导的伤害性参数（机械性和冷觉异常性疼痛以及疼痛情感动机行为）的影响，以及对单次给予阿那曲唑（0.2毫克/千克，口服）和两种抗肿瘤药物联合给药诱导的小鼠疼痛样症状（机械性异常性疼痛、肌肉力量和疼痛情感动机行为）的影响。香叶木素降低了紫杉醇和阿那曲唑诱导的伤害性参数。此外，我们观察到阿那曲唑加剧了紫杉醇诱导的机械性异常性疼痛，而香叶木素也能逆转这种作用。这些结果表明，香叶木素可能是治疗由紫杉醇和阿那曲唑等抗肿瘤药物引起的疼痛症状的有效治疗选择。
