Assessment of mechanisms involved in antinociception caused by sesquiterpene polygodial

Polygodial, a sesquiterpene isolated from the bark of Drymis winteri given systemically, intraplantarly, or by spinal or supraspinal sites, produced a ntinociception when assessed in both phases of the formalin test and agains t capsaicin-induced pain. Polygodial, even at high doses, had no antinocice ptive or antihyperalgesic effect when assessed in hot-plate assay or in glu tamate-induced hyperalgesia, nor did it significantly interfere with the mo tor coordination of animals when tested in the rota-rod test. The polygodia l antinociception assessed in the formalin test was not affected by i.p. tr eatment of animals with cyprodime, yohimbine, phaclofen, bicuculine, or nit ric oxide precursor or by intrathecal administration of potassium channel b lockers 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] acet amide, p-chlorophenylalanine, prazosin, or by i.c.v. treatment with pertuss is toxin. In addition, polygodial antinociception was not cross-tolerant to morphine, nor was its effect affected by the adrenalectomy of animals. Tog ether, these results show that polygodial produces pronounced systemic, spi nal, and supraspinal antinociception in mice, mainly preventing the neuroge nic pain produced by formalin and capsaicin. The mechanism by which polygod ial produces antinociception seems likely to involve an interaction with th e opioid system, mainly kappa and delta subtypes, depend on the activation of G(i/o) protein sensitive to pertussis toxin, alpha(1)-adrenoceptors, and the serotoninergic system. Collectively, these results suggest that polygo dial itself or its derivatives may have potential therapeutic value for the development of new analgesic drugs.