Universität zu Köln

Klein, Ines and Lehmann, Helmar C. (2021). Pathomechanisms of Paclitaxel-Induced Peripheral Neuropathy. Toxics, 9 (10). BASEL: MDPI. ISSN 2305-6304

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Abstract

Peripheral neuropathy is one of the most common side effects of chemotherapy, affecting up to 60% of all cancer patients receiving chemotherapy. Moreover, paclitaxel induces neuropathy in up to 97% of all gynecological and urological cancer patients. In cancer cells, paclitaxel induces cell death via microtubule stabilization interrupting cell mitosis. However, paclitaxel also affects cells of the central and peripheral nervous system. The main symptoms are pain and numbness in hands and feet due to paclitaxel accumulation in the dorsal root ganglia. This review describes in detail the pathomechanisms of paclitaxel in the peripheral nervous system. Symptoms occur due to a length-dependent axonal sensory neuropathy, where axons are symmetrically damaged and die back. Due to microtubule stabilization, axonal transport is disrupted, leading to ATP undersupply and oxidative stress. Moreover, mitochondria morphology is altered during paclitaxel treatment. A key player in pain sensation and axonal damage is the paclitaxel-induced inflammation in the spinal cord as well as the dorsal root ganglia. An increased expression of chemokines and cytokines such as IL-1 beta, IL-8, and TNF-alpha, but also CXCR4, RAGE, CXCL1, CXCL12, CX3CL1, and C3 promote glial activation and accumulation, and pain sensation. These findings are further elucidated in this review.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Helmar C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-569676
DOI:	10.3390/toxics9100229
Journal or Publication Title:	Toxics
Volume:	9
Number:	10
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2305-6304
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DORSAL-ROOT GANGLION; ACETYL-L-CARNITINE; OXIDATIVE STRESS; SENSORY NEURONS; CANCER; PAIN; AGENTS; TAXOL; ACTIVATION; TAXANES Multiple languages Environmental Sciences; Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56967