The DOI matches its Crossref record; 77 of the 79 references it cites were found in a registry or an index.
A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel
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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“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 the citing paper
“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]
Citations
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Regression Analysis for Correlated Data
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Research works printed but not linked: 2
- Fan, 1999, Possible mechanisms of paclitaxel-induced apoptosis., Biochem Pharmacol, 57, 1215
- Polomano, 1998, Paclitaxel-induced painful peripheral neuropathy in rats., Soc Neurosci Abstr, 24, 381
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The biopsychosocial approach to chronic pain: Scientific advances and future directions.
Gatchel, R. J., Peng, Y. B., Peters, M. L., Fuchs, P. N., & Turk, D. C. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.4.581 · Cited by 3,392
Models and Mechanisms of Hyperalgesia and Allodynia
Sandkühler, J. (2009) · Physiological Reviews · doi:10.1152/physrev.00025.2008 · Cited by 1,148
Pathological pain and the neuroimmune interface
Grace, P. M., Hutchinson, M. R., Maier, S. F., & Watkins, L. R. (2014) · Nature reviews. Immunology · doi:10.1038/nri3621 · Cited by 982
Chemokines, neuronal–glial interactions, and central processing of neuropathic pain
Gao, Y., & Ji, R. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.01.002 · Cited by 636
Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy
Flatters, S. J. L., & Bennett, G. J. (2004) · Pain · doi:10.1016/j.pain.2004.01.029 · Cited by 576
Metadata
- 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.
- Venue
- Pain
- Published
- 2001-12
- Volume
- 94
- Issue
- 3
- Pages
- 293-304
- ISSN
- 0304-3959 (ISSN-L)
- 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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