Oxaliplatin-induced neuropathic pain in cancer: animal models and related research progress

Abstract

Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, has shown substantial efficacy in cancer treatment. However, its associated side effects, particularly chemotherapy-induced peripheral neuropathic pain (CIPNP), continue to challenge cancer survivors globally. Clinically, it frequently presents as numbness, coldness, and discomfort in the limbs and extremities. Duloxetine is advised for analgesic purposes. Despite its clinical relevance, both the application methods and the underlying mechanisms of oxaliplatin-induced CINP warrant further investigation. Consequently, more precise animal models are needed to explore the mechanisms and progression of this condition. This review consolidates recent advancements in rat and mouse models of oxaliplatin-induced CINP, with the aim of enhancing modeling success rates and developing models that more accurately mirror disease progression. Such models are essential for advancing clinical research and drug development.

Keywords: CINP animal model; applications; chemotherapy; neuropathic pain; oxaliplatin.

FIGURE 1

This figure provides a detailed illustration of the modeling process and subsequent evaluation methods for oxaliplatin-induced effects in rats and mice.

FIGURE 2

Conduct relevant behavioral and other tests on the successfully modeled rats. (A) Mechanical pain threshold testing (Von Frey hair, Randall-Selitto paw-withdrawal test, Dynamic Aesthesiometer Test); (B,C) Mechanical nociceptive hypersensitivity testing (Von Frey fiber wire method, Randall-Selitto); (D) Cold nociceptive hypersensitivity test (Cold plate method4°C, acetone test, Cold water bath rat tail withdrawal method, Cold paw test); (E) Thermal nociceptive hypersensitivity testing (Hot plate test method 50°C ± 1°C, Thermal radiation method, Hot water bath mouse tail immersion experiment, Hargreaves test); (F) Motor coordination testing (Rotarod test, Motor strength grip test). This figure was created using Figdraw.

FIGURE 3

Oxaliplatin generates acute neuropathic pain by disrupting voltage-gated ion channels, activating TRP channels, reducing DNA transcription, causing mitochondrial malfunction, and leading to the emergence of reactive oxygen species (ROS). This figure was created using Bio Render.

FIGURE 4

Oxaliplatin activates TRPA1 channels on the membranes of dorsal root ganglion (DRG) neurons, facilitating Ca²⁺ influx, leading to the accumulation of ROS, resulting in mitochondrial DNA (mtDNA) damage, disruption of the electron transport chain, and the opening of the mitochondrial permeability transition pore (mPTP). These alterations subsequently impede ATP synthesis and facilitate neurotoxicity. This figure was created using BioRender.

FIGURE 5

Activation of TRPA1 leads to Ca²⁺ influx, which ultimately results in mitochondrial dysfunction and neurotoxicity. mPTP:mitochondrial permeability transition pore,MCU: Mitochondrial Calcium Uniporter, mtDNA: mitochondrial DNA. This figure was created using BioRender.