GINSENOSIDE RF, A TRACE COMPONENT OF GINSENG ROOT, PRODUCES ANTINOCICEPTION IN MICE

Ginseng root, a traditional oriental medicine, contains more than a do zen biologically active saponins called ginsenosides, including one pr esent in only trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits Ca2+ channels in mammalian sensory neurons th rough a mechanism requiring G-proteins, whereas a variety of other gin senosides were relatively ineffective. Since inhibition of Ca2+ channe ls in sensory neurons contributes to antinociception by opioids, we te sted for analgesic actions of Rf. We find dose-dependent antinocicepti on by systemic administration of Rf in mice using two separate assays of tonic pain: in the acetic acid abdominal constriction test, the EDS , was 56 +/- 9 mg/kg, a concentration similar to those reported for as pirin and acetaminophen in the same assay; in the tonic phase of the b iphasic formalin test, the ED50 was 129 +/- 32 mg/kg. Rf failed to aff ect nociception measured in three assays of acute pain: the acute phas e of the formalin test, and the thermal (49 degrees C) tail-flick and increasing-temperature (3 degrees C/min) hot-plate tests. The simplest explanation is that Rf inhibits tonic pain without affecting acute pa in, but other possibilities exist. Seeking a cellular explanation for the effect, we tested whether Rf suppresses Ca2+ channels on identifie d nociceptors. Inhibition was seen on large, but not small, nociceptor s. This is inconsistent with a selective effect on tonic pain, so it s eems unlikely that Ca2+ channel inhibition on primary sensory neurons can fully explain the behavioral antinociception we have demonstrated for Rf. (C) 1998 Elsevier Science B.V.