Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms?

Neurosci Lett. 2015 Jun 2;596:90-107. doi: 10.1016/j.neulet.2014.10.014. Epub 2014 Oct 22.

Abstract

Cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib are some of the most effective drugs successfully employed (alone or in combinations) as first-line treatment for common cancers. However they often caused severe peripheral neurotoxicity and neuropathic pain. Structural deficits in Dorsal Root Ganglia and sensory nerves caused symptoms as sensory loss, paresthesia, dysaesthesia and numbness that result in patient' suffering and also limit the life-saving therapy. Several scientists have explored the various mechanisms involved in the onset of chemotherapy-related peripheral neurotoxicity identifying molecular targets useful for the development of selected neuroprotective strategies. Dorsal Root Ganglia sensory neurons, satellite cells, Schwann cells, as well as neuronal and glial cells in the spinal cord, are the preferential sites in which chemotherapy neurotoxicity occurs. DNA damage, alterations in cellular system repairs, mitochondria changes, increased intracellular reactive oxygen species, alterations in ion channels, glutamate signalling, MAP-kinases and nociceptors ectopic activation are among the events that trigger the onset of peripheral neurotoxicity and neuropathic pain. In the present work we review the role of the main players in determining the pathogenesis of anticancer drugs-induced peripheral neuropathy.

Keywords: Chemotherapy drugs; Dorsal Root Ganglia; Neuropathic pain; Peripheral nerves; Peripheral neurotoxicity.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • DNA Damage
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / physiopathology
  • Glutamic Acid / metabolism
  • Humans
  • Ion Channels / metabolism
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuralgia / chemically induced
  • Neuralgia / metabolism
  • Neuralgia / physiopathology
  • Neuroglia / drug effects
  • Neuroglia / physiology
  • Oxidative Stress
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / physiopathology
  • Satellite Cells, Perineuronal / drug effects
  • Satellite Cells, Perineuronal / physiology
  • Schwann Cells / drug effects
  • Schwann Cells / physiology
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Ion Channels
  • Glutamic Acid
  • Mitogen-Activated Protein Kinases