Evidence of TRPV1 receptor and PKC signaling pathway in the antinociceptive effect of amyrin octanoate

• Published in: Brain research Vol. 1295; pp. 76 - 88
• Main Authors: Marcon, Rodrigo, Luiz, Ana Paula, de Paula Werner, Maria Fernanda, Freitas, Cristina Setim, Hatsuko Baggio, Cristiane, Pinto do Nascimento, Francisney, Soldi, Cristian, Pizzolatti, Moacir Geraldo, Soares Santos, Adair Roberto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 12.10.2009
• Subjects: Acetic Acid; Amiryn octanoate; Analgesics - administration & dosage; Analysis of Variance; Animals; Capsaicin; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Dose-Response Relationship, Drug; Female; Hot Temperature; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Male; Mice; Motor Activity - drug effects; Neurology; Neurons - drug effects; Neurons - metabolism; Nociception; Oleanolic Acid - administration & dosage; Oleanolic Acid - analogs & derivatives; Opioid Peptides - metabolism; Pain - chemically induced; Pain - drug therapy; Pain Measurement; Physical Stimulation; Protein Kinase C - metabolism; Psychomotor Performance - drug effects; Rats; Rats, Wistar; Serotonin - metabolism; Signal Transduction - drug effects; TRPV Cation Channels - metabolism; α, β-amyrin; Nociception; Amiryn octanoate; Capsaicin; α, β-amyrin; Hyperalgesia
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.07.073

Abstract Previous studies from our group investigated the antinociceptive property of amyrin octanoate, a synthetic compound derivative from natural precursor α, β-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 ID50 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 ID50 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 Gi/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 E2 . 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.