Breaking the Feedback Loop: A Model of Vicious Cycle for CIPN and Acupuncture-Medication Combination.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and often debilitating complication of cancer therapy, whose chronicity and refractoriness cannot be adequately explained by traditional linear etiological models. This review proposes and organizes a "vicious cycle" model as a hypothesis: initial neuronal injury caused by chemotherapeutic agents initiates a self-sustaining positive feedback loop in which mitochondrial dysfunction and oxidative stress reciprocally amplify each other, thereby activating neuroinflammation and ion channel remodeling. These processes collectively drive neuronal hyperexcitability, which further exacerbates mitochondrial damage and inflammatory responses, ultimately establishing a pathological circuit composed of multiple interconnected nodes. Building on this hypothesized framework, the article systematically evaluates current therapeutic strategies. Many conventional pharmacological interventions predominantly focus on specific targets. While some exhibit pleiotropic effects, the difficulty in disrupting the integrated dynamics of the entire cycle may partially explain their limited disease-modifying capabilities. In contrast, traditional Chinese medicine (TCM)-through the synergistic multi-target effects of acupuncture, bioactive herbal constituents, and compound formulations-shows potential to concurrently modulate several critical nodes within the cycle, suggesting promising advantages in holistic regulation, despite the preliminary and heterogeneous nature of current supporting evidence. On this basis, we propose an integrative "acupuncture combined with herbal medicine" strategy: acupuncture may enable rapid modulation of the neuro-immune network, whereas herbal medicine may support sustained repair of molecular pathways, together potentially contributing to disruption of the pathological cycle from microscopic mechanisms to macroscopic phenotypes. This approach advocates a paradigm shift in CIPN management-from symptom control toward breaking the pathological cycle-and offers a novel theoretical framework and integrated therapeutic pathway for further investigation of this persistent clinical challenge.