Figure 2.

Bimodal (Excitatory and Inhibitory) Opioid Modulation System in the Dorsal Horn. Opioids appear to have differential effects on the opioid receptor in the dorsal root ganglion based on whether it activates the traditional G_I/G_O protein inhibitory mode leading to analgesia or a newly identified Gs protein excitatory receptor that can produce hyperalgesia. Figure 2a shows the effect of low dose opioids (1–10 nM), which preferentially activates the excitatory (Gs coupled) mode and masks the inhibitory (Gi/Go) mode leading to hyperalgesia. More typically high dose opioids are used (figure 2b) where there is preferential activation of the inhibitory mode and masking of the excitatory mode. With the chronic use of opioids there is again sensitization and unmasking of the excitatory mode and tolerance of the inhibitory mode leading to hyperalgesia. Low doses of opioid antagonists like naltrexone, naloxone or buprenorphone have selective inhibitory effects on the excitatory pathways which enhances morphine activity.