Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice.
Ginseng root, a traditional oriental medicine, contains more than a dozen biologically active saponins called ginsenosides, including one present in only trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits Ca2+ channels in mammalian sensory neurons through a mechanism requiring G-proteins, whereas a variety of other ginsenosides were relatively ineffective. Since inhibition of Ca2+ channels in sensory neurons contributes to antinociception by opioids, we tested for analgesic actions of Rf. We find dose-dependent antinociception by systemic administration of Rf in mice using two separate assays of tonic pain: in the acetic acid abdominal constriction test, the ED50 was 56+/-9 mg/kg, a concentration similar to those reported for aspirin and acetaminophen in the same assay; in the tonic phase of the biphasic formalin test, the ED50 was 129+/-32 mg/kg. Rf failed to affect nociception measured in three assays of acute pain: the acute phase 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 pain, but other possibilities exist. Seeking a cellular explanation for the effect, we tested whether Rf suppresses Ca2+ channels on identified nociceptors. Inhibition was seen on large, but not small, nociceptors. This is inconsistent with a selective effect on tonic pain, so it seems unlikely that Ca2+ channel inhibition on primary sensory neurons can fully explain the behavioral antinociception we have demonstrated for Rf.
Mogil
J S
JS
Dept. of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA. jmogil@s.psych.uiuc.edu
Shin
Y H
YH
McCleskey
E W
EW
Kim
S C
SC
Nah
S Y
SY
D000009:Abdominal Muscles / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D036145:Ginsenosides; D006358:Hot Temperature; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D005894:Panax; D018408:Patch-Clamp Techniques; D010946:Plants, Medicinal; D012503:Saponins / Q000494:pharmacology*; D013623:Tail
D000700:Analgesics; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D036145:Ginsenosides; D012503:Saponins; D005557:Formaldehyde; C055328:ginsenoside Rf