빈크리스틴 유발 말초신경병증의 병태생리학적 기전: 실험동물 모델 연구를 중심으로 한 고찰

Pathophysiological Mechanisms of Vincristine-Induced Peripheral Neuropathy: Focusing on Experimental Animal Models

Vincristine-induced peripheral neuropathy (VIPN) is a dose- limiting complication significantly impairing quality of life in patients undergoing chemotherapy. Despite its clinical importance, the pathophysiological mechanisms underlying VIPN remain incompletely understood, and effective prevention or treatment strategies are limited. This review systematically examines the multifaceted pathophysiological mechanisms of VIPN elucidated through rodent experimental models, with emphasis on their translational relevance to companion animal clinical practice. VIPN pathogenesis involves multiple interconnected mechanisms rather than a single pathway. Key mechanisms include: (1) microtubule dysfunction and axonal transport impairment leading to energy depletion and neurotrophic factor deficiency; (2) mitochondrial dysfunction and oxidative stress characterized by increased ROS production; (3) neuroinflammation involving NLRP3 inflammasome activation, pro-inflammatory cytokine release, and glial cell activation in both peripheral and central nervous systems; (4) altered expression and function of ion channels resulting in neuronal hyperexcitability; and (5) dysregulation of signaling pathways including MAPK, NF-κB, and PI3K/Akt/mTOR. These mechanisms interact to create a vicious cycle that amplifies and perpetuates neuropathic pain. Importantly, similar clinical manifestations and histopathological findings have been reported in dogs and cats receiving vincristine therapy, suggesting that mechanistic insights from rodent models have translational value for veterinary oncology. However, species-specific differences in drug metabolism and toxicity profiles must be considered when applying therapeutic strategies across species. This integrative approach linking experimental animal research with human and veterinary clinical practice may contribute to improved quality of life for all patients suffering from VIPN.