Elsevier

Toxicology

Volume 291, Issues 1–3, 27 January 2012, Pages 1-9
Toxicology

Review
Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy

https://doi.org/10.1016/j.tox.2011.10.019Get rights and content

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.

Abbreviations

CIPN
cancer chemotherapy-induced peripheral neuropathy
CGRP
calcitonin gene related peptide
cGMP
cyclic guanosine monophosphate
CRPS-I
complex regional pain syndrome
Cyt C
cytochrome C
DRG
dorsal root ganglia
ERK
extracellular signal regulated kinase
IENF
intraepidermal nerve fibers
JNK/Sapk
c-Jun N-terminal kinase/stress-activated protein kinases
LC cells
Langerhans cells
MAPK
mitogen activated protein kinase
mETC
mitochondrial electron transport chain
MMP-3
matrix metalloproteinase-3
mPTP
mitochondrial permeability transition pore
nNOS
neuronal NOS
NMDA
N-methyl-d-aspartate
NR2B
NMDA receptors subtype
PKC
protein kinase C
3PGDH
3-phosphoglycerate dehydrogenase
TREK1
TWIK(Tandem of P domains in a Weak Inward rectifying K+ channel) RElated K+ channels
TRAAK
TWIK related arachidonic acid activated K+ channels
HCNs
hyperpolarization-activated channels
TRPV
transient receptor potential vanilloid
TRPA1
transient receptor potential ankyrin 1
TRPM8
transient receptor potential melastatin 8

Keywords

Cancer-chemotherapeutic drugs
Peripheral neuropathy
Mitochondria
Calcium
Oxidative stress
Inflammation

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