Mini-Review: Mitochondrial dysfunction and chemotherapy-induced neuropathic pain

Area of Science:

• Neuroscience
• Oncology
• Mitochondrial Biology

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of cancer treatment.
• CIPN can cause long-lasting neuropathic pain, significantly impacting patient quality of life and treatment adherence.
• Mitochondrial dysfunction in peripheral sensory nerves is increasingly recognized as a key mechanism underlying CIPN.

Purpose of the Study:

• To review the evidence linking chemotherapeutic agents to mitochondrial injury in peripheral sensory nerves.
• To explore the mechanisms by which mitochondrial dysfunction leads to CIPN.
• To discuss current and emerging strategies targeting mitochondrial health for CIPN prevention and treatment.

Main Methods:

• Review of preclinical and clinical studies on chemotherapy-induced peripheral neuropathy.
• Analysis of research investigating the role of mitochondrial structure, bioenergetics, and dynamics in CIPN.
• Examination of therapeutic strategies aimed at mitigating mitochondrial damage in sensory neurons.

Main Results:

• Chemotherapeutic agents disrupt mitochondrial structure, bioenergetics, and transport, leading to increased oxidative stress.
• Accumulation of dysfunctional mitochondria in sensory neurons causes axonal defects and nerve fiber loss.
• Mitochondrial dysfunction contributes to neuronal hyperexcitability and central sensitization, establishing chronic pain.

Conclusions:

• The mitotoxicity theory provides a framework for understanding CIPN pathogenesis.
• Strategies enhancing mitochondrial function have shown efficacy in preclinical models.
• Targeting mitochondrial dysfunction represents a promising therapeutic avenue for managing CIPN.