Tags

Type your tag names separated by a space and hit enter

CB2 cannabinoid receptor-mediated peripheral antinociception.
Pain. 2001 Sep; 93(3):239-245.PAIN

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.

Authors+Show Affiliations

Department of Anesthesiology and Pharmacology, University of Arizona, Tucson, AZ 85724, USA Departments of Medicinal Chemistry and Molecular and Cell Biology, The University of Connecticut, Storrs, CT 06269, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11514083

Citation

Malan, Philip T., et al. "CB2 Cannabinoid Receptor-mediated Peripheral Antinociception." Pain, vol. 93, no. 3, 2001, pp. 239-245.
Malan PT, Ibrahim MM, Deng H, et al. CB2 cannabinoid receptor-mediated peripheral antinociception. Pain. 2001;93(3):239-245.
Malan, P. T., Ibrahim, M. M., Deng, H., Liu, Q., Mata, H. P., Vanderah, T., Porreca, F., & Makriyannis, A. (2001). CB2 cannabinoid receptor-mediated peripheral antinociception. Pain, 93(3), 239-245. https://doi.org/10.1016/S0304-3959(01)00321-9
Malan PT, et al. CB2 Cannabinoid Receptor-mediated Peripheral Antinociception. Pain. 2001;93(3):239-245. PubMed PMID: 11514083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB2 cannabinoid receptor-mediated peripheral antinociception. AU - Malan,Philip T,Jr AU - Ibrahim,Mohab M, AU - Deng,Hongfeng, AU - Liu,Qian, AU - Mata,Heriberto P, AU - Vanderah,Todd, AU - Porreca,Frank, AU - Makriyannis,Alexandros, PY - 2001/8/22/pubmed PY - 2002/1/5/medline PY - 2001/8/22/entrez SP - 239 EP - 245 JF - Pain JO - Pain VL - 93 IS - 3 N2 - 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. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/11514083/CB2_cannabinoid_receptor_mediated_peripheral_antinociception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-200109000-00006 DB - PRIME DP - Unbound Medicine ER -