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Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats.
Br J Pharmacol 2007; 152(5):765-77BJ

Abstract

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 CB1/CB2 receptor agonist WIN55,212-2, the receptor-inactive enantiomer WIN55,212-3, the CB2-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 CB1 (SR141716) or CB2 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 CB1 (SR141716) and CB2 (SR144528) antagonists blocked the anti-allodynic effects of WIN55,212-2. (R,S)-AM1241 suppressed vincristine-induced mechanical hypersensitivity through a CB2 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 CB1 and CB2 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 CB1 and CB2 receptors. These anti-allodynic effects are mediated, at least in part, at the level of the spinal cord.

Authors+Show Affiliations

Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA 30602-3013, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17572696

Citation

Rahn, E J., et al. "Activation of Cannabinoid CB1 and CB2 Receptors Suppresses Neuropathic Nociception Evoked By the Chemotherapeutic Agent Vincristine in Rats." British Journal of Pharmacology, vol. 152, no. 5, 2007, pp. 765-77.
Rahn EJ, Makriyannis A, Hohmann AG. Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. Br J Pharmacol. 2007;152(5):765-77.
Rahn, E. J., Makriyannis, A., & Hohmann, A. G. (2007). Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. British Journal of Pharmacology, 152(5), pp. 765-77.
Rahn EJ, Makriyannis A, Hohmann AG. Activation of Cannabinoid CB1 and CB2 Receptors Suppresses Neuropathic Nociception Evoked By the Chemotherapeutic Agent Vincristine in Rats. Br J Pharmacol. 2007;152(5):765-77. PubMed PMID: 17572696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. AU - Rahn,E J, AU - Makriyannis,A, AU - Hohmann,A G, Y1 - 2007/06/18/ PY - 2007/6/19/pubmed PY - 2008/2/26/medline PY - 2007/6/19/entrez SP - 765 EP - 77 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 152 IS - 5 N2 - 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 CB1/CB2 receptor agonist WIN55,212-2, the receptor-inactive enantiomer WIN55,212-3, the CB2-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 CB1 (SR141716) or CB2 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 CB1 (SR141716) and CB2 (SR144528) antagonists blocked the anti-allodynic effects of WIN55,212-2. (R,S)-AM1241 suppressed vincristine-induced mechanical hypersensitivity through a CB2 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 CB1 and CB2 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 CB1 and CB2 receptors. These anti-allodynic effects are mediated, at least in part, at the level of the spinal cord. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17572696/Activation_of_cannabinoid_CB1_and_CB2_receptors_suppresses_neuropathic_nociception_evoked_by_the_chemotherapeutic_agent_vincristine_in_rats_ L2 - https://doi.org/10.1038/sj.bjp.0707333 DB - PRIME DP - Unbound Medicine ER -