Two compounds boost morphine's painkilling effects when injected into mice.

Morphine and other opioids induce inflammation in the central nervous system, which can suppress pain relief and lead to opioid dependence. Hang Yin at the University of Colorado at Boulder and his team show that morphine causes inflammation by binding to the protein MD2, which, in turn, causes the protein to bind to an immune-system receptor called TLR4. In cultured cells, this process activates TLR4 signalling and the release of inflammatory molecules.

Injecting mice with two synthetic compounds known to block MD2 binding to TLR4 enhanced morphine-induced analgesia. Interfering with TLR4 signalling could be a promising strategy for improving painkilling therapies, the authors say.

Proc. Natl Acad. Sci. USA (2012)