Intrathecal treatments with ginsenosides produce antinociceptive effect on proinflammatory cytokines-induced pain behavior in mice

Proinflammatory cytokines have been implicated in the production of neuropathic pain. We have previously reported that several ginsenosides produce antinoception. Especially, we have previously demonstrated that ginsenosides administered supraspinally reduce pain behaviors induced by proinflmmatory cytokines administered spinally. However, spinal action of ginsenosides in the regulation of proinflammtory cytokine-induced pain behavior has not been characterized yet. In the present study, we investigated the effects of ginsenosides following intrathecal treatment on pain behaviors induced by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-), interleukin-1 (IL-1), and interferon- (IFN-) injected intrathecally. The ginsenosides such as R-b1, R-b2, R-c, R-f, R-g1, and R-g3 pretreated intrathecally reduced the pain behavior induced by TNF-, IL-1, and IFN- injection. However, ginsenoside R-d and R-e treated intrathecally did not affect the pain behavior induced by proinflammatory cytokines injected spinally. Our findings suggest that some ginsenosides may exert the antinociceptive effects in pro-inflammatory cytokine-induced pain model, when they are administered spinally.