The underlying bases of the considerable interindividual variability in pai
n-related traits are starting to be revealed. Although the relative importa
nce of genes versus experience in human pain perception remains unclear, ro
dent populations display large and heritable differences in both nociceptiv
e and analgesic sensitivity. The identification and characterization of par
ticularly divergent populations provides a powerful Initial step in the gen
etic analysis of pain, because these models can be exploited to identify ge
nes contributing to the behavior-level variability. Ultimately, DNA sequenc
e differences representing the differential alleles at pain-relevant genes
can be identified. Thus, by using a combination of "top-down" and "bottom-u
p" strategies, we are now able to genetically dissect even complex biologic
al traits like pain. The present review summarizes the current progress tow
ard these ends in both humans and rodents.