Vincristine hyperalgesia in the rat: A model of painful vincristine neuropathy in humans
Abstract
To investigate the mechanism of vincristine-induced pain in humans undergoing chemotherapy we have established a model of vincristine-induced hyperalgesia in rat. Vincristine (100 micrograms/kg) was administered daily over a period of two weeks. An acute dose-dependent decrease in mechanical nociceptive threshold and an increased response to non-noxious mechanical stimuli ("hyperalgesia") occurred after the second day of administration. Chronic lowered threshold and increased response to stimuli (determined 24 h after each injection) was first noted during the second week of vincristine administration. Responses gradually returned to baseline during the two weeks following discontinuation of treatment. Vincristine also increased sensitivity to heat stimulation. At a dose that produced hyperalgesia (100 micrograms/kg), vincristine did not cause a significant motor deficit. Peripheral administration of a mu-opioid agonist did not reduce vincristine-induced acute hyperalgesia. Hyperalgesia induced by vincristine in the rat provides a good model for the experimental study of painful peripheral neuropathies in human patients receiving vincristine as a chemotherapeutic agent.
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In rats, 10 daily injections of vincristine (0.02, 0.1, or 0.2 mg/kg, intravenous) with a 2-day drug-free interval after the fifth day induced hyperalgesia and allodynia.
“In rats, 10 daily injections of vincristine (0.02, 0.1, or 0.2 mg/kg, intravenous) with a 2-day drug-free interval after the fifth day, induced hyperalgesia (Aley et al, 1996), and allodynia (Authier et al, 1999).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Aley et al, 1996
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- Authors
- Aley, K. O., Reichling, D. B., & Levine, J. D.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Levine, J.D.
- ORCID
- Levine, J.D.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1996-07
- Volume
- 73
- Issue
- 1
- Pages
- 259-265
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2004637463
- Cited by
- 185
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 9 · 2016: 1 · 2015: 4 · 2014: 9 · 2013: 10 · 2012: 9
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- vincristine, chemotherapy-induced peripheral neuropathy, hyperalgesia, peripheral neuropathic pain, mechanical nociception, thermal sensitivity, mu-opioid receptor, animal models
- MeSH terms
- Analgesics, Animals, Antineoplastic Agents, Phytogenic, Disease Models, Animal, Enkephalins, Hot Temperature, Hyperalgesia, Injections, Intravenous, Male, Neurons, Afferent, Peripheral Nervous System Diseases, Physical Stimulation, Psychomotor Performance, Vincristine, Rats, Sprague-Dawley, Pain Threshold, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Rats
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