A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats
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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Mixed CB1/CB2 receptor agonists and CB2 receptor-selective agonists are effective against paclitaxel-induced peripheral neuropathy.
“It has been reported that mixed CB 1 /CB 2 receptor agonists and CB 2 receptor-selective agonists are effective against paclitaxel-induced peripheral neuropathy (Deng et al, 2015a(Deng et al, , 2015b;;Pascual et al, 2005;Rahn et al, 2008).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Pascual et al, 2005
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 [119]
WIN55,212-2 suppressed neuropathic nociception in the paclitaxel model but had no effect on body temperature or immobility.
“WIN55,212-2 suppressed neuropathic nociception in this model but had no effect on body temperature or immobility.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [119]
WIN55,212-2-induced decreases in spontaneous motor activity were observed in the paclitaxel model.
“WIN55,212-2-induced decreases in spontaneous motor activity were nonetheless observed.119”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [119]
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- Authors
- Pascual, D., Goicoechea, C., Suardíaz, M., & Martín, M. I.
- Affiliations
- Universidad Rey Juan Carlos (ES)
- Venue
- Pain
- Published
- 2005-11
- Volume
- 118
- Issue
- 1
- Pages
- 23-34
- ISSN
- 0304-3959 (ISSN-L)
- 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 › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › 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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