Cited by 95Pain Mechanisms and TreatmentsCancer Treatment and PharmacologyCannabis and Cannabinoid Research

The Maintenance of Cisplatin- and Paclitaxel-Induced Mechanical and Cold Allodynia is Suppressed by Cannabinoid CB2 Receptor Activation and Independent of CXCR4 Signaling in Models of Chemotherapy-Induced Peripheral Neuropathy

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Deng, Liting, Guindon, Josée, Vemuri, V Kiran, Thakur, Ganesh A, White, Fletcher A, Makriyannis, Alexandros, Hohmann, Andrea G·2012·Molecular Pain

Abstract

Background: Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone 2 agonist, produces antinociception without producing central nervous system (CNS)-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel). A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4) signaling to both chemotherapy-induced neuropathy and CB 2 agonist efficacy. Results: AM1710 (0.1, 1 or 5 mg/kg i.p.) suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB 2 antagonist AM630 (3 mg/kg i.p.), but not the CB 1 antagonist AM251 (3 mg/kg i.p.), consistent with a CB 2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p.) failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions: Our results indicate that activation of cannabinoid CB 2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB 2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.

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  • AM1710 suppressed the maintenance of mechanical and cold allodynia in the cisplatin model through a CB2 receptor mechanism of action, with no evidence of CB1 receptor involvement.

    “Conversely, AM1710 suppressed the maintenance of mechanical and cold allodynia in the cisplatin model through a CB 2 receptor mechanism of action, with no evidence of CB 1 receptor involvement (Deng et al, 2012).”

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Authors
Deng, L., Guindon, J., Vemuri, V. K., Thakur, G. A., White, F. A., Makriyannis, A., & Hohmann, A. G.
Affiliations
  • Indiana University Bloomington (US)
  • Center for Drug Discovery, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA
  • Northeastern University (US)
  • Indiana University School of Medicine (US)
Corresponding author
Hohmann, Andrea G
Venue
Molecular Pain
Published
2012-01-01
Volume
8
Pages
71-71
ISSN
1744-8069 (ISSN-L)
OpenAlex
W2097659456
Cited by
94
References
74
Citations by year
2026: 1 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 1
FWCI
4.50
Type
journal article
Language
en
Open access
Locations
  • Molecular Pain (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Funders
National Institute on Drug Abuse (DA3801, DA 9158, R01DA026040, DA028200, R01DA021644, RC1DA028200, P01DA009158, DA021644, DA026040)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Keywords
chemotherapy-induced peripheral neuropathy, CB2 receptor, cisplatin, paclitaxel, mechanical allodynia, cold allodynia, CXCR4 signaling, neuropathic pain, antinociception, AM630, AMD3100, CB1 receptor
MeSH terms
Cyclams, Animals, Benzylamines, Chromones, Cisplatin, Disease Models, Animal, Heterocyclic Compounds, Hyperalgesia, Indoles, Male, Peripheral Nervous System Diseases, Piperidines, Pyrazoles, Time Factors, Signal Transduction, Treatment Outcome, Rats, Sprague-Dawley, Paclitaxel, Receptors, CXCR4, Receptor, Cannabinoid, CB2, Rats, Cryopyrin-Associated Periodic Syndromes

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