Combined intervention of

Introduction: Oxaliplatin-induced peripheral neuropathy (OIPN) is a major dose-limiting neurotoxic side effect that severely disrupts quality of life and compromises antitumor efficacy. Despite its clinical prevalence, effective neuroprotective strategies remain elusive, and diagnosis largely relies on subjective symptom reporting rather than objective pathological assessment. Emerging evidence suggests that targeting the gut-peripheral nerve axis offers a novel therapeutic avenue/approach. Therefore, this study primarily aimed to investigate the combined neuroprotective efficacy of Methods: An OIPN rat model was established via tail vein injection of oxaliplatin. Sprague-Dawley rats were randomized by body weight into five groups: control, model, Results: Oxaliplatin administration induced a progressive neuropathy characterized by significant weight loss, mechanical allodynia, and cold allodynia. Histopathologically, neuronal atrophy, axonal degeneration, demyelination, and inflammatory infiltration were observed in the DRG and peripheral nerves, accompanied by a marked reduction in IENFD. Serological analysis indicated a systemic pro-inflammatory shift (elevated IL-6, IL-1β, and TNF-α; decreased IL-10) alongside a substantial elevation in NfL, a specific biomarker of axonal injury. All therapeutic interventions attenuated neuropathic pain, ameliorated structural nerve damage, modulated inflammatory cytokine profiles, and reduced serum NfL levels. Notably, combination therapy ( Conclusions: Our findings confirm that oxaliplatin triggers complex pathological alterations, including pain hypersensitivity, neuroinflammation, and axonal injury. The combinatorial treatment with