Research ArticlePain

Oligomerization of MrgC11 and μ-opioid receptors in sensory neurons enhances morphine analgesia

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Science Signaling  19 Jun 2018:
Vol. 11, Issue 535, eaao3134
DOI: 10.1126/scisignal.aao3134

A better way to use opioids?

Morphine and other opioids are excellent at reducing pain, but they have behavioral side effects and are addictive. He et al. found that the analgesic response to morphine could be enhanced by compounds that activate the peripheral sensory neuron–localized receptor MrgC11 in mice and MrgX in human cells. Activation of MrgC11 promoted its interaction with the opioid receptor MOR, which directed MOR’s intracellular signaling toward a G protein–mediated pathway that promoted its quick recycling to the cell surface. This enabled the use of lower doses of morphine to achieve pain relief in mice, without the tolerance and locomotor effects typically associated with morphine. These findings suggest that coactivating MrgX in patients may improve the use of opioids for treating pain.