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Papers of the Week

Papers: 26 Jun 2021 - 2 Jul 2021

Pharmacology/Drug Development

2021 Jun 25

Neurosci Lett

Mini-Review: Mitochondrial Dysfunction and Chemotherapy-induced Neuropathic Pain.


Doyle TM, Salvemini D
Neurosci Lett. 2021 Jun 25:136087.
PMID: 34182057.


Chemotherapy-induced peripheral neuropathy (CIPN) is a somatosensory small fiber axonopathy in cancer patients receiving any of a variety of widely-use antitumor agents. CIPN can lead to long-lasting neuropathic pain that limits the dose or length otherwise life-saving cancer therapy. Accumulating evidence over the last two decade indicates that many chemotherapeutic agents cause mitochondrial injury in the peripheral sensory nerves by disrupting mitochondrial structure and bioenergetics, increasing nitro-oxidative stress and altering mitochondrial transport, fission, fusion and mitophagy. The accumulation of abnormal and dysfunctional mitochondria in sensory neurons are linked axonal growth defects resulting in loss of intraepidermal nerve fibers in the hands and feet, increased spontaneous discharge and the sensitization of peripheral sensory neurons that provoke and promote changes in the central nervous system that establish chronic neuropathic pain. This has led to the propose mitotoxicity theory of CIPN. Strategies that improve mitochondrial function have shown success in preventing and reversing CIPN in pre-clinical animal models and have begun to show some progress toward translation to the clinic. In this review, we will review the evidence for, the causes and effects of and current strategies to target mitochondrial dysfunction in CIPN.