title: Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels.
abstract: OBJECTIVE
  The effects of several potassium (K(+)) channel blockers were studied to determine which K(+) channels are involved in peripheral antinociception induced by the cannabinoid receptor agonist, anandamide.
  
  
  METHODS
  Hyperalgesia was induced by subcutaneous injection of 250 μg carrageenan into the plantar surface of the hind paw of rats. The extent of hyperalgesia was measured using a paw pressure test 3 h following carrageenan injection. The weight in grams (g) that elicited a nociceptive response, paw flexion, during the paw pressure test was used as the nociceptive response threshold.
  
  
  RESULTS
  Doses of 50, 75, and 100 ng of anandamide elicited a dose-dependent antinociceptive effect. Following a 100 ng dose of anandamide no antinociception was observed in the paw that was contralateral to the anandamide injection site, which shows that anandamide has a peripheral site of action. Pretreatment with 20, 40 and 80 μg AM251, a CB(1) receptor antagonist, caused a dose-dependent decrease in anandamide-induced antinociception, suggesting that the CB(1) receptor is directly involved in anandamide effect. Treatment with 40, 80 and 160 μg glibenclamide, an ATP-sensitive K(+) channel blocker, caused a dose-dependent reversal of anandamide-induced peripheral antinociception. Treatment with other K(+) channel antagonists, tetraethylammonium (30 μg), paxilline (10 μg) and dequalinium (50 μg), had no effect on the induction of peripheral antinociception by anandamide.
  
  
  CONCLUSIONS
  This study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist, anandamide, is primarily caused by activation of ATP-sensitive K(+) channels and does not involve other potassium channels.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31270-100, Belo Horizonte, Brazil.
authors.forename: Gláucia Maria Lopes
authors.initials: GM
authors.lastname: Reis
authors.forename: Marina Abadia
authors.initials: MA
authors.lastname: Ramos
authors.forename: Daniela da Fonseca
authors.initials: Dda F
authors.lastname: Pacheco
authors.forename: André
authors.initials: A
authors.lastname: Klein
authors.forename: Andréa Castro
authors.initials: AC
authors.lastname: Perez
authors.forename: Igor Dimitri Gama
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D054086:KATP Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D054086:KATP Channels; D053284:Polyunsaturated Alkamides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043884:Receptor, Cannabinoid, CB1; C078814:anandamide