PROJECT: JTC 2025 - Pain: VASC-inPAIN

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and often irreversible side effect of neurotoxic chemotherapeutic agents, particularly oxaliplatin, used in colon cancer treatment. A hallmark of CIPN is chronic neuropathic pain, significantly reducing patients? quality of life. Despite affecting over 70% of patients, no effective treatment exists. While research has predominantly focused on neuronal damage, emerging evidence suggests that vascular dysfunction?specifically blood-nerve barrier disruption and reduced nerve perfusion?plays a key role in CIPN-associated pain. VASC-in-PAIN is a consortium-driven project investigating vascular dysfunction in oxaliplatin-induced pain and exploring vasodilators as a therapeutic strategy. Using preclinical models and patient data, we will determine whether restoring blood flow mitigates neuropathy while preserving oxaliplatin?s anti-tumor efficacy. Our multidisciplinary approach encompasses (1) chronic CIPN mouse models to assess long-term effects of vasodilators, (2) molecular and cellular pain mechanisms studies in peripheral nerves, dorsal root ganglia and spinal cord, (3) evaluating vasodilator impact on chemotherapy efficacy in tumor-bearing mice, (4) extending to other neurotoxic chemotherapies, and (5) retrospective patient data analysis. By targeting the vascular component of CIPN, this project aims to reposition vasodilators as a novel therapeutic strategy, addressing a critical unmet medical need.