Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin.
The present studies were conducted to test the hypothesis that activation of peripheral cannabinoid CB(2) receptors would suppress hyperalgesia evoked by intradermal administration of capsaicin, the pungent ingredient in hot chili peppers. The CB(2)-selective cannabinoid agonist (2-iodo-5-nitro-phenyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-methanone (AM1241) (33, 330 microg/kg i.p.) suppressed the development of capsaicin-evoked thermal and mechanical hyperalgesia and allodynia. AM1241 also produced a dose-dependent suppression of capsaicin-evoked nocifensive behavior. The AM1241-induced suppression of each parameter of capsaicin-evoked pain behavior was completely blocked by the CB(2) antagonist N-[(1S)-endo-1,3,3-trimethyl bicycle [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) but not by the CB(1) antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A). AM1241 (33 microg/kg i.pl.) suppressed capsaicin-evoked thermal and mechanical hyperalgesia and allodynia after local administration to the capsaicin-treated (ipsilateral) paw but was inactive after administration to the capsaicin-untreated (contralateral) paw. Our data indicate that AM1241 suppresses capsaicin-evoked hyperalgesia and allodynia through a local site of action. These data provide evidence that actions at cannabinoid CB(2) receptors are sufficient to normalize nociceptive thresholds and produce antinociception in persistent pain states.
Hohmann
Andrea G
AG
Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA 30602-3013, USA. ahomann@uga.edu
Farthing
Jesse N
JN
Zvonok
Alexander M
AM
Makriyannis
Alexandros
A
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D002186:Cannabinoids / Q000378:metabolism; D002211:Capsaicin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy*; D007271:Injections, Intradermal; D008297:Male; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism*
C439263:AM 1241; D000700:Analgesics; D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2; D002211:Capsaicin