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Cited by 483Cancer Treatment and PharmacologyPain Mechanisms and TreatmentsChemotherapy-related skin toxicity

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
DOI 10.1016/s0304-3959(01)00363-3
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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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Crossref · 10.1016/s0304-3959(01)00363-3

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  • A more recent study using the same paclitaxel dosing paradigm reported the presence of mechanical allodynia and the absence of thermal hyperalgesia.

    “A more recent study using the same paclitaxel dosing paradigm118 reported the presence of mechanical allodynia and the absence of thermal hyperalgesia.85”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [118]

  • In one study, paclitaxel produced mechanical allodynia starting on day 5 that continued throughout the timecourse, although thermal hyperalgesia was only present from days 18-21.

    “In one study, paclitaxel118 produced mechanical allodynia starting on day 5 that continued throughout the timecourse, although thermal hyperalgesia was only present from days 18-21.119”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [118]

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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
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 › 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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