Oleanolic acid, a pentacyclic triterpene attenuates capsaicin-induced nociception in mice: possible mechanisms.
The anti-inflammatory pentacyclic triterpene, oleanolic acid (OA) was examined on acute nociception induced by intraplantar injection of capsaicin in mice. OA administered orally to mice at 10, 30 and 100 mgkg(-1), significantly attenuated the paw-licking response to capsaicin (1.6 microg/paw) by 53%, 68.5% and 36.6%, respectively. Ruthenium red (3 mgkg(-1), s.c.), a non-competitive vanilloid receptor (V1, TRPV1)-antagonist also suppressed the capsaicin nociception by 38.6%. The maximal antinociception produced by 30 mgkg(-1) OA was significantly blocked in animals pre-treated with naloxone (2 mgkg(-1), i.p.), the opioid antagonist; l-arginine (600 mgkg(-1), i.p.), the substrate for nitric oxide synthase; or glibenclamide (2 mgkg(-1), i.p.), the K(ATP)-channel blocker, but was unaffected by yohimbine (2 mgkg(-1), i.p.), an alpha(2)-adrenoceptor antagonist. In open-field and rota-rod tests that detect motor deficits, mice received 30 mgkg(-1) OA did not manifest any effect per se, indicating that the observed antinociception is not a consequence of motor abnormality. These data suggest that OA inhibits capsaicin-evoked acute nociception due to mechanisms possibly involving endogenous opioids, nitric oxide, and K(ATP)-channel opening.
Maia
Juliana L
JL
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
Lima-Júnior
Roberto C P
RC
Melo
Caroline M
CM
David
Juceni P
JP
David
Jorge M
JM
Campos
Adriana R
AR
Santos
Flávia A
FA
Rao
Vietla S N
VS
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004396:Coloring Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels; D019686:Lamiaceae / Q000737:chemistry; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009828:Oleanolic Acid / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism; D012430:Ruthenium Red; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D054086:KATP Channels; D009292:Narcotic Antagonists; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D012430:Ruthenium Red; D015016:Yohimbine; D009270:Naloxone; D009828:Oleanolic Acid; D009020:Morphine; D002211:Capsaicin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester