Exploring Serum Biomarkers for Neuropathic Pain in Rat Models of Chemotherapy-Induced Peripheral Neuropathy: A Comparative Pilot Study with Oxaliplatin, Paclitaxel, Bortezomib, and Vincristine

Author:

Balayssac David12ORCID,Durif Julie3,Lambert Céline4ORCID,Dalbos Cristelle2,Chapuy Eric2,Etienne Monique5,Demiot Claire6ORCID,Busserolles Jérôme2ORCID,Martin Vincent57ORCID,Sapin Vincent8ORCID

Affiliation:

1. Direction de la Recherche Clinique et de l’Innovation, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France

2. INSERM U1107 NEURO-DOL, Université Clermont Auvergne, F-63000 Clermont-Ferrand, France

3. Laboratoire de Biochimie et de Génétique Moléculaire, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France

4. Unité de Biostatistiques, Direction de la Recherche Clinique et de l’Innovation, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France

5. Metabolic Adaptations to Exercise under Physiological and Pathological Conditions (AME2P), Université Clermont Auvergne, F-63000 Clermont-Ferrand, France

6. UR 20218—Neuropathies et Innovations Thérapeutiques (NeurIT), Faculties of Medicine and Pharmacy, University of Limoges, F-87025 Limoges, France

7. Institut Universitaire de France (IUF), F-75000 Paris, France

8. Laboratoire de Biochimie et de Génétique Moléculaire, CNRS, INSERM, iGReD, CHU Clermont-Ferrand, Université Clermont Auvergne, F-63000 Clermont-Ferrand, France

Abstract

Blood biomarkers, including neurofilament light chain (NfL), have garnered attention as potential indicators for chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting adverse effect of neurotoxic anticancer drugs. However, no blood biomarker has been established for routine application or translational research. This pilot study aimed to evaluate a limited panel of blood biomarkers in rat models of CIPN and their correlations with neuropathic pain. CIPN models were induced through repeated injections of oxaliplatin, paclitaxel, bortezomib, and vincristine. Electronic von Frey testing was used to assess tactile allodynia. Post anticancer injections, serum concentrations of 31 proteins were measured. Allodynia thresholds decreased in anticancer-treated animals compared to controls. No consistent modifications were observed in the biomarkers across CIPN models. The most noteworthy biomarkers with increased concentrations in at least two CIPN models were NfL (paclitaxel, vincristine), MCP-1, and RANTES (oxaliplatin, vincristine). Vincristine-treated animals exhibited strong correlations between LIX, MCP-1, NfL, and VEGF concentrations and tactile allodynia thresholds. No single biomarker can be recommended as a unique indicator of CIPN-related pain. Because of the study limitations (single dose of each anticancer drug, young animals, and single time measurement of biomarkers), further investigations are necessary to define the kinetics, specificities, and sensitivities of MCP-1, RANTES, and NfL.

Funder

NeuroDeRisk project

Innovative Medicines Initiative

European Union’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations

CHU Clermont-Ferrand

Publisher

MDPI AG

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Toxicology

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