Fecal Microbiota\nTransplantation-Mediated Rebalancing\nof the Gut–Brain Axis Alleviates Cisplatin-Induced Neuropathic\nPain

Chemotherapy-induced neuropathic pain (CINP) presents\na significant\nchallenge in cancer treatment, necessitating novel therapeutic approaches.\nThe intricate relationship between CINP and the gut–brain axis\nindicates a crucial role for the gut microbiota in pain modulation\nduring cancer therapy. In this study, we investigated the effect of\ngut microbiota and their modulation on CINP in rats. Cisplatin administration\n(20 mg/kg, ip) disrupted the integrity of the blood-spinal cord barrier,\nas evidenced by reduced expression of tight junction proteins occludin\nand claudin-5 and increased leakage of pro-inflammatory cytokines\ninto the spinal cord. Fecal microbiota transplantation (FMT, 0.5 mL\nof P.O.) from healthy rats over 21 days restored barrier integrity,\nas confirmed by Evan’s blue assay. FMT intervention halted\nthe progression of cisplatin-induced pain, demonstrated through a\nbattery of pain assays assessing mechanical, thermal, and cold allodynia\nalongside hyperalgesia measurements. Additionally, FMT treatment reduced\noxidative stress and modulated neuro-inflammatory markers, resulting\nin a rebalanced cytokine profile with decreased levels of neuro-inflammatory\ncytokines (IL-6 and TNFα) and increased expression of the anti-inflammatory\ncytokine IL-10. Gut microbiota-mediated IL-1β/NF-κB signaling\nemerged as a critical factor in leukocyte recruitment and microglial\nactivation, highlighting the gut–brain axis as a key regulatory\nnexus in managing cisplatin-induced neuropathic pain. These findings\nunderscore the therapeutic potential of targeting gut microbiota modulation\nas a promising strategy for alleviating CINP and improving the well-being\nof cancer patients undergoing chemotherapy.