Evidence of TRPV1 receptor and PKC signaling pathway in the antinociceptive effect of amyrin octanoate.
Previous studies from our group investigated the antinociceptive property of amyrin octanoate, a synthetic compound derivative from natural precursor alpha, beta-amyrin, against nociceptive response induced by acetic acid and formalin. Here, we investigated some of the mechanisms of action underlying the antinociceptive effects of amyrin octanoate. Amyrin octanoate given intraperitoneally (0.001-1 mg /kg) or intrathecally (10-1000 ng /site) caused dose-dependent and long-lasting inhibition of acetic acid-induced visceral nociception, with mean ID(50) values of 0.003 (0.001-0.005) mg/kg and 122.4 (60.8-246.6) ng/site, respectively. In the capsaicin- and glutamate-induced paw licking, amyrin octanoate caused significant and dose-dependent inhibition of both nociceptive responses, with ID(50) values of 1.36 and 0.04 mg/kg, respectively. Furthermore, amyrin octanoate also reduced significantly the nociception caused by intrathecal injection of glutamate, substance P and capsaicin, with inhibitions of 36+/-11%, 67+/-10% and 78+/-5%, respectively. The antinociception caused by amyrin octanoate in the acetic acid test was significantly attenuated by neonatal pretreatment of mice with capsaicin, but seems to involve mechanisms independent of G(i/o) protein, opioidergic, serotonergic, noradrenergic and cholinergic system, since it was not affected by pertussis toxin, naloxone, yohimbine, mecamylamine or atropine. In addition, amyrin octanoate reduced thermal and mechanical hyperalgesia induced by bradykinin and phorbol myristate acetate in rats, without affecting similar responses caused by prostaglandin E(2). Taken together, the present results shown that octanoate amyrin produces antinociceptive and antihyperalgesic effects, through an interaction with capsaicin-sensitive fibers and the inhibition of the PKC signaling pathway.
Marcon
Rodrigo
R
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.
Luiz
Ana Paula
AP
Werner
Maria Fernanda de Paula
MF
Freitas
Cristina Setim
CS
Baggio
Cristiane Hatsuko
CH
Nascimento
Francisney Pinto do
FP
Soldi
Cristian
C
Pizzolatti
Moacir Geraldo
MG
Santos
Adair Roberto Soares
AR
D019342:Acetic Acid; D000700:Analgesics / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018847:Opioid Peptides / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism*
D000700:Analgesics; D018847:Opioid Peptides; D050916:TRPV Cation Channels; D012701:Serotonin; D009828:Oleanolic Acid; D011493:Protein Kinase C; C036380:beta-amyrin; C071423:capsazepine; D019342:Acetic Acid; D002211:Capsaicin