Cited by 482Cancer Treatment and PharmacologyPain Mechanisms and TreatmentsChemotherapy-related skin toxicity

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A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel

Polomano, Rosemary C., Mannes, Andrew J., Clark, Uraina S., Bennett, Gary J.·2001·Pain

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Abstract

Paclitaxel, an effective anti-neoplastic agent in the treatment of solid tumors, produces a dose-limiting painful peripheral neuropathy in a clinically significant number of cancer patients. Prior work has demonstrated paclitaxel-induced neurodegeneration and sensory loss in laboratory rodents. We describe here an experimental paclitaxel-induced painful peripheral neuropathy. Adult male rats were given four intraperitoneal injections on alternate days of vehicle or 0.5, 1.0, or 2.0 mg/kg of paclitaxel (Taxol). Behavioral tests for pain using mechanical and thermal stimuli applied to the tail and hind paws, and tests for motor performance, were taken before, during and after dosing for 22-35 days. All three doses of paclitaxel caused heat-hyperalgesia, mechano-allodynia, mechano-hyperalgesia, and cold-allodynia, but had no effect on motor performance. Neuropathic pain began within days and lasted for several weeks. We did not detect any dose-response relationship. Tests at the distal, mid, and proximal tail failed to show evidence of a length-dependent neuropathy. Vehicle control injections had no effect on any measure. No significant systemic toxicities were noted in the paclitaxel-treated animals. Light-microscopic inspection of the sciatic nerve (mid-thigh level), L4-L5 dorsal root ganglia, and dorsal and ventral roots, and the gray and white matter of the L4-L5 spinal cord, showed no structural abnormalities. Electron microscopic examination of the sciatic nerve (mid-thigh level) and the L4-L5 dorsal root ganglia and dorsal horns demonstrated no degeneration of myelinated and unmyelinated axons in the sciatic nerve and roots, but revealed endoneurial edema. This model may be useful in understanding a significant source of pain in cancer patients, and in finding ways to avoid the neurotoxicity that limits paclitaxel therapy.

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Authors: Polomano, R. C., Mannes, A. J., Clark, U. S., & Bennett, G. J.
Affiliations: Pennsylvania State University (US)
University of Pennsylvania (US)
Hahnemann University Hospital (US)
Corresponding author: Polomano, Rosemary C.
ORCID: Polomano, Rosemary C.
Mannes, Andrew J.
Clark, Uraina S.
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2001-12
Volume: 94
Issue: 3
Pages: 293-304
ISSN: 0304-3959 (ISSN-L)
DOI: 10.1016/s0304-3959(01)00363-3
OpenAlex: W1991677710
Cited by: 476
References: 79
Citations by year: 2026: 20 · 2025: 10 · 2024: 18 · 2023: 18 · 2022: 16 · 2021: 35 · 2020: 30 · 2019: 27 · 2018: 28 · 2017: 30 · 2016: 18 · 2015: 17 · 2014: 30 · 2013: 21 · 2012: 28
FWCI: 2.62
Type: journal article
Language: en
Open access: closed
Locations: Pain (publishedVersion)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
United States Pharmacopeia
National Institutes of Health (5k01nr000136-03)
National Institute of Nursing Research (KO1 NR 00136-01A1)
Topics: Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
Keywords: paclitaxel, chemotherapy-induced peripheral neuropathy, neuropathic pain, thermal hyperalgesia, mechanical allodynia, cold allodynia, sciatic nerve, dorsal root ganglia, endoneurial edema, axonal degeneration, rat model, dose-response relationship, length-dependent neuropathy
MeSH terms: Animals, Antineoplastic Agents, Phytogenic, Behavior, Animal, Cold Temperature, Disease Models, Animal, Hot Temperature, Hindlimb, Hyperalgesia, Male, Motor Activity, Peripheral Nervous System Diseases, Physical Stimulation, Tail, Rats, Sprague-Dawley, Paclitaxel, Rats

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A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel

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