Predicting the antinociceptive efficacy of σ(1) receptor ligands by a novel receptor fluorescence resonance energy transfer (FRET) based biosensor.

We have developed a novel methodology for monitoring the σ1 receptor activation switch in living cells. Our assay uncovered the intrinsic nature of σ1 receptor ligands by recording the ligand-mediated conformational changes of this chaperone protein. The change triggered by each ligand correlated well with its ability to attenuate formalin induced nociception in an animal model of pain. This tool may assist in predicting the antinociceptive efficacy of σ1 receptor ligands.