Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy.

Abstract

Anti-cancer drugs such as vincristine, paclitaxel, oxaliplatin, cisplatin and bortezomib are well reported to exert direct and indirect effects on sensory nerves to alter the amplitude of action potential, conduction velocity and induce pain. It results in patient suffering and also limits the treatment with potentially useful anticancer drugs. The different scientists have worked in this area to explore the mechanisms responsible for its pathogenesis. Anti-cancer agents activate plasma membrane localized ion channels on dorsal root ganglia and dorsal horn neurons including sodium, calcium, potassium, glutamate activated NMDA receptors to alter cytosolic ionic mileu particularly intracellular calcium that trigger secondary changes to induce neuropathic pain. These may include opening of mPTP pore on mitochondria to induce intracellular calcium release; activation of protein kinase C; phosphorylation of TRPV; activation of calpases/calpains; generation of nitric oxide and free radicals to induce cytotoxicity to axons and neuronal cell bodies. Furthermore, the inflammatory process initiated in glial cells and macrophages also trigger changes in the sensory neurons to alter nociceptive processing. The present review elaborates the role of all these individual targets in the pathogenesis of anticancer agents-induced neuropathic pain to develop effective therapeutic modalities for pain management.

• Authors: Amteshwar Singh Jaggi, Nirmal Singh
• Journal: Toxicology (Toxicology) Vol. 291 Issue 1-3 Pg. 1-9 (Jan 27 2012) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 22079234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Neuropeptides
• Potassium Channels
• Receptors, N-Methyl-D-Aspartate
• Receptors, Serotonin
• Sodium Channels
• TRPV Cation Channels
• Nitric Oxide
• Protein Kinase C
• Mitogen-Activated Protein Kinases
• Calpain
• Caspases
• Calcium

Topics

• Animals
• Antineoplastic Agents (toxicity)
• Calcium (metabolism)
• Calpain (metabolism)
• Caspases (metabolism)
• Humans
• Inflammation (chemically induced, pathology)
• Mitochondria (drug effects)
• Mitogen-Activated Protein Kinases (metabolism)
• Nerve Fibers (drug effects)
• Neuropeptides (metabolism)
• Nitric Oxide (metabolism)
• Peripheral Nervous System Diseases (chemically induced, pathology)
• Potassium Channels (metabolism)
• Protein Kinase C (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Receptors, Serotonin (metabolism)
• Sodium Channels (metabolism)
• TRPV Cation Channels (metabolism)