Itchiness is a common side effect of morphine use. Zhou-Feng Chen at Washington University in St. Louis, Missouri, and his colleagues demonstrate that itchiness is caused by a different morphine receptor from that involved in pain relief.
The drug binds to a receptor called MOR, which has various subtypes, including MOR1 and MOR1D. Silencing MOR1 lessened the pain-killing effect of morphine in mice, whereas knocking down MOR1D dampened scratching behaviour, but had no effect on pain relief. Furthermore, only MOR1D interacts with another receptor called GRPR, which is involved in mediating itch.
Inhibiting proteins that are downstream of GRPR in the same pathway blocked the itchiness but not the analgesic effects of morphine.