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Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats
Open accessAbstract
Background and purpose: The ability of cannabinoids to suppress mechanical hypersensitivity (mechanical allodynia) induced by treatment with the chemotherapeutic agent vincristine was evaluated in rats. Sites of action were subsequently identified. Experimental approach: Mechanical hypersensitivity developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same times. Effects of the CB 1/CB 2 receptor agonist WIN55,212‐2, the receptor‐inactive enantiomer WIN55,212‐3, the CB 2‐selective agonist (R,S)‐AM1241, the opiate agonist morphine and vehicle on chemotherapy‐induced neuropathy were evaluated. WIN55,212‐2 was administered intrathecally (i.t.) or locally in the hindpaw to identify sites of action. Pharmacological specificity was established using competitive antagonists for CB 1 (SR141716) or CB 2 receptors (SR144528). Key results: Systemic administration of WIN55,212‐2, but not WIN55,212‐3, suppressed vincristine‐evoked mechanical allodynia. A leftward shift in the dose‐response curve was observed following WIN55,212‐2 relative to morphine treatment. The CB 1 (SR141716) and CB 2 (SR144528) antagonists blocked the anti‐allodynic effects of WIN55,212‐2. (R,S)‐AM1241 suppressed vincristine‐induced mechanical hypersensitivity through a CB 2 mechanism. Both cannabinoid agonists suppressed vincristine‐induced mechanical hypersensitivity without inducing catalepsy. Spinal sites of action are implicated in cannabinoid modulation of chemotherapy‐induced neuropathy. WIN55,212‐2, but not WIN55,212‐3, administered i.t. suppressed vincristine‐evoked mechanical hypersensitivity at doses that were inactive following local hindpaw administration. Spinal coadministration of both the CB 1 and CB 2 antagonists blocked the anti‐allodynic effects of WIN55,212‐2. Conclusions and implications: Cannabinoids suppress the maintenance of vincristine‐induced mechanical allodynia through activation of CB 1 and CB 2 receptors. These anti‐allodynic effects are mediated, at least in part, at the level of the spinal cord. British Journal of Pharmacology (2007) 152, 765–777; doi:10.1038/sj.bjp.0707333; published online 18 June 2007
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In the citing paper
“These effects were blocked by intrathecal co-administration of rimonabant and SR144528, implicating both CB 1 and CB 2 receptors (Rahn et al, 2007).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rahn et al, 2007
In the citing paper
“In particular, systemic administration of WIN55,212-2 suppresses vincristine-evoked mechanical allodynia through a CB 1 and CB 2 -dependent mechanism.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rahn et al, 2007
In the citing paper
“Spinal administration of WIN55,212-2 suppressed vincristineevoked mechanical hypersensitivity at doses that were inactive following intraplantar administration.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rahn et al, 2007
In the citing paper
“In addition, AM1241 reverses vincristine-induced mechanical hypersensitivity through a CB 2 receptor mechanism of action.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rahn et al, 2007
In the citing paper
“Mixed CB 1 /CB 2 receptor agonists and CB 2 selective receptor agonists reduce nociceptive behavior in vincristine-treated rats (Rahn et al, 2007) (see Table 5).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rahn et al, 2007
In the citing paper
“Systemic and intrathecal, but not intraplantar, WIN55,212-2 suppressed vincristine-induced mechanical allodynia through activation of CB1 and CB2 receptors.122”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [122]
In the citing paper
“Systemic (R,S)-AM1241 also partially reversed vincristine-induced mechanical allodynia in a CB2-dependent manner.122”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [122]
In the citing paper
“The anti-allodynic effects of WIN55,212-2 and (R,S)-AM1241 were observed at doses that did not produce intrinsic effects on motor behavior in the bar test.122”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [122]
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Self-citationIncreased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
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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
Cited by
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Guindon, J., & Hohmann, A. G. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707531 · Cited by 423
Self-citationCannabinoids and Pain: New Insights From Old Molecules
Vučković, S., Srebro, D., Vujović, K. S., Vučetić, Č., & Prostran, M. S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01259 · Cited by 440
Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
Rahn, E. J., & Hohmann, A. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.002 · Cited by 305
Self-citationDonvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301
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Metadata
- Authors
- Rahn, E. J., Makriyannis, A., & Hohmann, A. G.
- Affiliations
- University of Georgia (US)
- Northeastern University (US)
- Corresponding author
- Hohmann, A G
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2007-11
- Volume
- 152
- Issue
- 5
- Pages
- 765-777
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2190028
- OpenAlex
- W1542530495
- Cited by
- 146
- References
- 70
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 11 · 2021: 11 · 2020: 15 · 2019: 5 · 2018: 8 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 10 · 2012: 11
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Psi Chi
- American Psychological Association of Graduate Students
- National Institute on Drug Abuse (DA3801, DA022478, DA 9158, R01DA003801, R21DA022478, R01DA021644, R01DA014022, R37DA003801, DA014022, P01DA009158, DA021644)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- CB1 receptor, CB2 receptor, vincristine, chemotherapy-induced peripheral neuropathy, mechanical allodynia, neuropathic pain, WIN 55,212-2, SR141716, SR144528, morphine, spinal cord, intrathecal administration
- MeSH terms
- Rimonabant, Animals, Body Weight, Camphanes, Cannabinoids, Catalepsy, Dose-Response Relationship, Drug, Hindlimb, Hyperesthesia, Injections, Intraperitoneal, Injections, Spinal, Male, Morphine, Morpholines, Naphthalenes, Neuralgia, Pain Measurement, Physical Stimulation, Piperidines, Pyrazoles, Thermosensing, Vincristine, Rats, Sprague-Dawley, Pain Threshold, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Benzoxazines, Rats
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