Figure 6.

Model for the regulation of mu opioid receptor (MOR) signaling by Hsp90 in the brain. This summary model combines results from this manuscript with our earlier work using non-selective Hsp90 inhibitors in the brain (Lei et al., 2017). Together this data suggests that Hsp90α, p23, and Cdc37 act in concert in the brain to promote the phosphorylation of ERK MAPK by the MOR in response to opioid drugs, thus promoting opioid anti-nociception. Treatment with non-selective or selective inhibitors blocks this role, thus blocking ERK MAPK phosphorylation and blocking anti-nociception in response to opioids.