Effects of female sex hormones on chemotherapeutic paclitaxel-induced neuropathic pain and involvement of inflammatory signal

Abstract

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.