In summary, this is the first electrophysiological study to employ an animal model and examine the functional consequence of the A118G polymorphism in sensory neurons with regard to opioid-mediated Ca2+ current inhibition. The experiments were performed in neurons that had comparable biophysical parameters. The data for the morphine pharmacological profile of the 118GG carriers illustrated a diminished potency and efficacy resembling the clinical, behavioral, and in vitro observations. On the other hand, no significant pharmacological differences between both groups of neurons were observed when fentanyl was employed. From the data we conclude that the use of the humanized mouse line will be a valuable tool to further explore the signal transduction pathways that mediate the changes in morphine pharmacology in 118GG patients.
