Further antinociceptive effects of myricitrin in chemical models of overt nociception in mice

The present 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 (10-100 mg/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 (100 mg/kg, i.p.) and camphor (7.6 mg/kg, s.c.) in 43 +/- 10% and 57 +/- 8%, respectively. Myricitrin (30-100 mg/kg, i.p.) and amiloride (100 mg/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 (3 mg/kg, i.p.) significantly reduced the nociception induced by menthol (1.2 mu mol/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 100 mg/kg, i.p.) markedly reduced menthol-induced mechanical allodynia. However, myricitrin (100 mg/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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.