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Br J Pharmacol. 2015 Jan;172(2):364-74. doi: 10.1111/bph.12653. Epub 2014 Jul 1.

Opioid receptor trafficking and interaction in nociceptors.

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  • 1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai, China.


Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy.


This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit


dorsal root ganglion; morphine antinociceptive tolerance; nociceptor; receptor interaction; receptor trafficking; δ-opioid receptor; μ-opioid receptor

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