Unlike the effects described with morphine above, the fentanyl pharmacological profile of 118AA and 118GG sensory neurons was similar. These results differ from two clinical studies which have reported that 118G allele carriers required more12 or less5 fentanyl for anesthesia than 118A carriers. It is unclear why fentanyl-mediated Ca2+ channel inhibition would be comparable in both types of sensory neurons in our mouse model and exert a different effect in the clinical setting5,27. Our model system consists of acutely dissociated neurons, and thus, the influence of other neurons (either pre- or postsynaptically) or glial cells is removed. Further, under our recording conditions, the temporal resolution is in the ms to s range and the exposure of the neurons to the receptor agonists is limited. The conditions observed in vivo are significantly more complex. In the clinical setting, for instance, there are varied routes of administration; morphine metabolism that is influenced by gender, age, disease state; and different rates of elimination.
