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A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats

Pascual, David, Goicoechea, Carlos, Suardíaz, Margarita, Martín, María Isabel·2005·Pain

DOI 10.1016/j.pain.2005.07.008

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Abstract

Paclitaxel is an effective antineoplastic drug treatment used as an anti-tumoral therapy. Unfortunately its use is associated with unwanted side effects, which include the development of peripheral neuropathies and neuropathic pain, greatly affecting the quality of life of patients. It is well known that agonists of the cannabinoid receptor are able to reduce hyperalgesia and allodynia that develop after nerve injury. Our aim was to evaluate the efficacy of the cannabinoid agonist WIN 55,212-2 to reduce the thermal hyperalgesia and the tactile allodynia induced by administration of paclitaxel in rats. Present results demonstrate that WIN 55,212-2 (1 mg/kg i.p.) significantly reduced the heat (P<0.0001) and the mechanical (P=0.0003) withdrawal thresholds, the dose being smaller than that required to reach similar effects in the sciatic nerve constriction model (1.5 mg/kg). When the cannabinoid tetrad test was evaluated to measure behavioral modifications, it was found that WIN 55,212-2 (1mg/kg) did not induce changes either in body temperature or in immobility time, and only a reduction in spontaneous motility was recorded. This effect was antagonized by SR 141716A, suggesting the involvement of the CB1 receptor, although the participation of CB2 receptors cannot be excluded from this study. When WIN 55,212-2 was administered intraplantar, no differences were observed between the injected paw and the contralateral paw, suggesting that systemic mechanisms are needed to reach effectiveness. From these results we suggest that cannabinoids may be an interesting alternative to reduce neuropathic symptoms induced by paclitaxel, however more work is required to assess this possibility.

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Authors: Pascual, D., Goicoechea, C., Suardíaz, M., & Martín, M. I.
Affiliations: Universidad Rey Juan Carlos (ES)
ORCID: Pascual, David
Goicoechea, Carlos
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2005-11
Volume: 118
Issue: 1
Pages: 23-34
ISSN: 0304-3959 (ISSN-L)
DOI: 10.1016/j.pain.2005.07.008
OpenAlex: W2038770419
Cited by: 117
References: 56
Citations by year: 2026: 2 · 2025: 2 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 10 · 2019: 8 · 2018: 10 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 7 · 2012: 9
FWCI: 3.80
Type: journal article
Language: en
Open access: closed
Locations: Pain (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords: WIN 55,212-2, cannabinoid receptor agonists, paclitaxel-induced peripheral neuropathy, neuropathic pain, thermal hyperalgesia, mechanical allodynia, CB1 receptor, CB2 receptor, SR141716A, peripheral neuropathy, antinociception
MeSH terms: Analgesics, Animals, Antineoplastic Agents, Phytogenic, Behavior, Animal, Cannabinoids, Disease Models, Animal, Hot Temperature, Humans, Hyperalgesia, Male, Morpholines, Naphthalenes, Neuralgia, Pain Measurement, Peripheral Nervous System Diseases, Physical Stimulation, Sensory Thresholds, Touch, Treatment Outcome, Rats, Wistar, Paclitaxel, Benzoxazines, Rats

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A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats

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