Vol. 292, Issue 1, 164-172, January 2000

Assessment of Mechanisms Involved in Antinociception Caused by Sesquiterpene Polygodial¹

Gilboé L. Mendes, Adair R. S. Santos , Angela Malheiros, Valdir Cechinel Filho, Rosendo A. Yunes and João B. Calixto

Departments of Pharmacology, Center of Biological Science (G.L.M., A.R.S.S., J.B.C.) and Chemistry, Center of Physical and Mathematical Science (A.M., R.A.Y.), Universidade Federal de Santa Catarina, Florianópolis; and Núcleo de Investigações Químico-Farmacêuticas, Centro de Ciências da Saúde, Universidade do Vale do Itajaí (A.R.S.S., V.C.F.), Itajaí, Brazil

Polygodial, a sesquiterpene isolated from the bark of Drymis winteri given systemically, intraplantarly, or by spinal or supraspinal sites, produced antinociception when assessed in both phases of the formalin test and against capsaicin-induced pain. Polygodial, even at high doses, had no antinociceptive or antihyperalgesic effect when assessed in hot-plate assay or in glutamate-induced hyperalgesia, nor did it significantly interfere with the motor coordination of animals when tested in the rota-rod test. The polygodial antinociception assessed in the formalin test was not affected by i.p. treatment of animals with cyprodime, yohimbine, phaclofen, bicuculine, or nitric oxide precursor or by intrathecal administration of potassium channel blockers such as apamin, charybdotoxin, glibenclamide, or tetraethylammonium. In contrast, polygodial antinociception was significantly attenuated by i.p. treatment of animals with naloxone, naltrindole, 2-(3,4-dichlorophenyl)-n-methyl-n-[(1S)-1-(3-isothiocynatophenyl)-2-(1-pryrolidinyl)ethyl]acetamide, p-chlorophenylalanine, prazosin, or by i.c.v. treatment with pertussis toxin. In addition, polygodial antinociception was not cross-tolerant to morphine, nor was its effect affected by the adrenalectomy of animals. Together, these results show that polygodial produces pronounced systemic, spinal, and supraspinal antinociception in mice, mainly preventing the neurogenic pain produced by formalin and capsaicin. The mechanism by which polygodial produces antinociception seems likely to involve an interaction with the opioid system, mainly  and  subtypes, depend on the activation of G_i/o protein sensitive to pertussis toxin, ₁-adrenoceptors, and the serotoninergic system. Collectively, these results suggest that polygodial itself or its derivatives may have potential therapeutic value for the development of new analgesic drugs.