CB2 cannabinoid receptor-mediated peripheral antinociception

Malan, Philip T.; Ibrahim, Mohab M.; Deng, Hongfeng; Liu, Qian; Mata, Heriberto P.; Vanderah, Todd; Porreca, Frank; Makriyannis, Alexandros

doi:10.1016/s0304-3959(01)00321-9

Cited by 391Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsIon Channels and Receptors

CB2 cannabinoid receptor-mediated peripheral antinociception

Malan, Philip T., Ibrahim, Mohab M., Deng, Hongfeng, Liu, Qian, Mata, Heriberto P., Vanderah, Todd, Porreca, Frank, Makriyannis, Alexandros·2001·Pain

DOI 10.1016/s0304-3959(01)00321-9

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Abstract

Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence implicates the CB(1) receptor in the production of antinociception. However, the capacity of CB(2) receptors, which are located outside the central nervous system (CNS), to produce antinociception is not known. Using AM1241, a CB(2) receptor-selective agonist, we demonstrate that CB(2) receptors produce antinociception to thermal stimuli. Injection of AM1241 in the hindpaw produced antinociception to a stimulus applied to the same paw. Injection of an equivalent dose of AM1241 into the paw contralateral to the side of testing did not. The antinociceptive actions of AM1241 were blocked by the CB(2) receptor-selective antagonist AM630, but not by the CB(1) receptor-selective antagonist AM251. AM1241 also produced antinociception when injected systemically (intraperitoneally). The antinociceptive actions of systemic AM1241 were blocked by injection of AM630 into the paw where the thermal stimulus was applied, but not the contralateral paw. These findings demonstrate the local, peripheral nature of CB(2) cannabinoid antinociception. AM1241 did not produce the CNS cannabinoid effects of hypothermia, catalepsy, inhibition of activity or impaired ambulation, while this tetrad of effects was produced by the mixed CB(1)/CB(2) receptor agonist WIN55,212-2. Peripheral antinociception without CNS effects is consistent with the peripheral distribution of CB(2) receptors. CB(2) receptor agonists may have promise clinically for the treatment of pain without CNS cannabinoid side effects.

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Authors: Malan, P. T., Ibrahim, M. M., Deng, H., Liu, Q., Mata, H. P., Vanderah, T., Porreca, F., & Makriyannis, A.
Affiliations: University of Arizona (US)
University of Connecticut (US)
Corresponding author: Malan, Philip T.
ORCID: Ibrahim, Mohab M.
Deng, Hongfeng
Liu, Qian
Vanderah, Todd
Porreca, Frank
Makriyannis, Alexandros
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2001-09
Volume: 93
Issue: 3
Pages: 239-245
ISSN: 0304-3959 (ISSN-L)
DOI: 10.1016/s0304-3959(01)00321-9
OpenAlex: W2070535004
Cited by: 391
References: 38
Citations by year: 2026: 5 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 13 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 14 · 2015: 8 · 2014: 12 · 2013: 23 · 2012: 9
FWCI: 8.68
Type: journal article
Language: en
Open access: closed
Locations: Pain (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k01da000283-04)
National Institute on Drug Abuse (DA 11823, DA 00283, R01DA011823)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: CB2 receptor, peripheral antinociception, AM1241, AM630, thermal pain, CB1 receptor, WIN 55,212-2, cannabinoid receptor agonists, pain management
MeSH terms: Analgesics, Animals, Cannabinoids, Indoles, Male, Morpholines, Naphthalenes, Pain Measurement, Piperidines, Pyrazoles, Receptors, Drug, Rats, Sprague-Dawley, Peripheral Nervous System, Receptors, Cannabinoid, Receptor, Cannabinoid, CB2, Benzoxazines, Rats

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CB2 cannabinoid receptor-mediated peripheral antinociception

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