Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of Neonatology, The First Hospital of Jilin University Changchun, Jilin, China.
J Biol Regul Homeost Agents. 2018 Sep-Oct;32(5):1157-1163.
Paclitaxel is used for the treatment of several types of cancers. However, one of its significant limiting complications is painful peripheral neuropathy during therapy. Gender is considered to play a role in modifying pain intensity. The present study examined the effects of female sex hormones on paclitaxel-induced neuropathic pain and the engagement of inflammatory signal of sensory nerves. Ovariectomies were performed on rats and subsequent hormone replacement with the combination of 17β-estradiol and progesterone was given. ELISA was used to determine the levels of proinflammatory cytokines (PICs) such as IL-1β, IL-6 and TNF-α in the dorsal root ganglion (DRG) of rats with different conditions of female sex hormones; moreover, Western blot analysis was used to examine expression of PIC receptors. The results of our study demonstrated that the increases of IL-1β, IL-6 and TNF-α; and expression of their respective receptors induced by paclitaxel were less in the DRG of ovariectomized rats with lack of female sex hormones. Thresholds of pain responses to mechanical and thermal stimuli appeared to be greater in ovariectomized rats with lack of female sex hormones. Overall, the findings indicate that circulating 17β-estradiol and progesterone contribute to the modulation of neuropathic pain response after administration of paclitaxel, likely via PIC signal in the sensory nerves, which is implicated to consider sex difference for pain management with application of chemotherapeutic paclitaxel.
紫杉醇用于治疗多种癌症。然而，其一个显著的限制并发症是治疗期间的疼痛性周围神经病变。性别被认为在调节疼痛强度方面起作用。本研究探讨了女性性激素对紫杉醇诱导的神经病理性疼痛的影响，以及感觉神经炎症信号的参与。对大鼠进行卵巢切除术，随后用 17β-雌二醇和孕酮的组合进行激素替代。ELISA 用于测定不同女性性激素条件下大鼠背根神经节 (DRG) 中促炎细胞因子 (PICs) 如 IL-1β、IL-6 和 TNF-α的水平；此外，还使用 Western blot 分析来检查 PIC 受体的表达。我们的研究结果表明，缺乏女性性激素的卵巢切除大鼠的 DRG 中，紫杉醇诱导的 IL-1β、IL-6 和 TNF-α的增加以及它们各自受体的表达减少。对机械和热刺激的疼痛反应阈值似乎在缺乏女性性激素的卵巢切除大鼠中更高。总体而言，这些发现表明循环中的 17β-雌二醇和孕酮有助于调节紫杉醇给药后的神经病理性疼痛反应，可能通过感觉神经中的 PIC 信号，这暗示在应用化疗紫杉醇治疗疼痛时要考虑性别差异。
