Research ArticlePain

Inhibition of Hsp90 in the spinal cord enhances the antinociceptive effects of morphine by activating an ERK-RSK pathway

See allHide authors and affiliations

Science Signaling  05 May 2020:
Vol. 13, Issue 630, eaaz1854
DOI: 10.1126/scisignal.aaz1854

Chaperones put the brakes on opioids

Until alternatives to opioids are developed, keeping opioid doses low but effective may be key to preventing their adverse effects. Duron et al. found that Hsp90 inhibitors injected into the spine of mice enhanced the efficacy of systemically administered opioids. In sensory neuron–rich regions of the spine, the chaperone protein Hsp90 attenuated the activity of a kinase-to-protein synthesis pathway required for the antinociceptive effects of opioids. In mice, blocking Hsp90 in the spine, but not in the brain or periphery, made opioids more effective at dampening sensitivity to heat and touch, suggesting that this approach might be beneficial in patients. Additional observations further suggest that the role of Hsp90 in opioid signaling is tissue specific.

View Full Text

Stay Connected to Science Signaling