title: Further antinociceptive effects of myricitrin in chemical models of overt nociception in mice.
abstract: The present work explored the antinociceptive effects of the flavonoid myricitrin in models of overt nociception triggered by intraplantar injection of chemical algogens into the hind paw of mice. The nociception induced by bradykinin (3 nmol/paw i.pl.) was abolished by prior treatment with myricitrin (10-100mg/kg, i.p.) with ID(50) of 12.4 (8.5-18.1)mg/kg. In sharp contrast, myricitrin failed to affect the nociception elicited by prostaglandin E(2) (3 nmol/paw i.pl.). Cinnamaldehyde (10 nmol/paw i.pl.)-induced nociception was reduced by myricitrin (100mg/kg, i.p.) and camphor (7.6 mg/kg,s.c.) in 43±10% and 57±8%, respectively. Myricitrin (30-100mg/kg, i.p.) and amiloride (100mg/kg, i.p.) inhibited nociceptive responses induced by acidified saline (pH 5/paw i.pl.), with ID(50) of 22.0 (16.1-30.0)mg/kg and inhibition of 71±6% and 64±5%, respectively. Moreover, myricitrin (10-30 mg/kg, i.p.) and ruthenium red (3mg/kg, i.p.) significantly reduced the nociception induced by menthol (1.2 μmol/paw i.pl.) with the mean ID(50) of 2.4 (1.5-3.7)mg/kg and inhibition of 95±3% and 51±7%, respectively. In addition, myricitrin administration (30 and 100mg/kg, i.p.) markedly reduced menthol-induced mechanical allodynia. However, myricitrin (100mg/kg, i.p.) prevented (only in time of 60 min) cold allodynia induced by menthol. Collectively, the present results extend prior data and show that myricitrin promotes potent antinociception, an action that is likely mediated by an inhibition of the activation of nociceptors by bradykinin and TRPs agonist (i.e. cinnamaldehyde, acidified saline and menthol), probably via inhibition of PKC pathways. Thus, myricitrin could constitute an attractive molecule of interest for the development of new analgesic drugs.
authors.affiliation: Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Trindade, Florianopolis 88040-900, SC, Brazil.
authors.forename: Marina Machado
authors.initials: MM
authors.lastname: Córdova
authors.forename: Maria Fernanda de Paula
authors.initials: MF
authors.lastname: Werner
authors.forename: Morgana Duarte da
authors.initials: MD
authors.lastname: Silva
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ruani
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000633:toxicity; D000584:Amiloride / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000633:toxicity; D002164:Camphor / Q000627:therapeutic use; D015232:Dinoprostone / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000627:therapeutic use*; D007839:Functional Laterality / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008956:Models, Chemical; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D012430:Ruthenium Red / Q000627:therapeutic use
chemical_list: D018712:Analgesics, Non-Narcotic; D005419:Flavonoids; D012430:Ruthenium Red; C008577:myricitrin; D002164:Camphor; D000171:Acrolein; D000584:Amiloride; D015232:Dinoprostone; D001920:Bradykinin; C012843:cinnamaldehyde