Ginsenoside Rb1 Attenuates Acute Inflammatory Nociception by Inhibition of Neuronal ERK Phosphorylation by Regulation of the Nrf2 and NF-κB Pathways

• Intrathecal introduction of ginsenoside-Rb1 (Rb1) decreased nociceptive behavior.
• Rb1 decreased activation of the proto-oncogene c-Fos in the spinal dorsal horn.
• Rb1 inhibited neuronal extracellular signal-regulated kinase phosphorylation.
• Rb1 activated the nuclear factor erythroid 2-related factor 2 pathway.
• Rb1 inhibited the nuclear factor kappa B pathway.

Ginsenoside-Rb1 (Rb1) has anti-inflammatory effects. However, the potential antinociceptive value of Rb1 for the treatment of acute inflammatory nociception is still unknown. In this study, we examined whether Rb1 has any antinociceptive effects on acute inflammatory nociception in Sprague Dawley rats given intrathecal (i.t.) introduction of Rb1 (2, 10, and 50 μg) 20 minutes before injection of formalin (5%, 50 μL) into the plantar surface of the hind paws. I.t. introduction of Rb1 significantly decreased nociceptive behavior during phase II (16–60 minutes), but not phase I (0–10 minutes), after formalin stimulation, corresponding to the reduced activation of c-Fos in the L4 to L5 spinal dorsal horn after formalin stimulation. Rb1 also reduced the phosphorylation of extracellular signal-regulated kinase in the neurons, but not the microglia and astrocytes. Microscopic examination of the microglia and astrocytes revealed no morphological changes due to formalin stimulation and i.t. introduction of Rb1. Interestingly, Rb1 activated the nuclear factor erythroid 2-related factor 2 pathway and inhibited nuclear factor kappa B pathways.PerspectiveOur findings indicate that i.t. introduction of Rb1 might effectively inhibit formalin-induced acute inflammatory nociception by inhibition of neuronal extracellular signal-regulated kinase phosphorylation, which is thought to regulate the nuclear factor erythroid 2-related factor 2 nuclear factor kappa B pathways in the spinal dorsal horn, which suggests therapeutic potential for suppression of acute inflammatory pain.