Screening for pain phenotypes: analysis of three congenic mouse strains on a battery of nine nociceptive assays.

In an attempt to identify new genes responsible for variability in pain sensitivity, we tested three congenic mouse strains--in which a small portion of the genome of the MOLF/Ei strain has been placed on a C57BL/6 genetic background--on a battery of nine nociceptive assays, chosen to reflect those assays in most common use in the pain literature. Mice of both sexes were evaluated by two different testers at different points in time, allowing us to examine the relative importance of genotype, sex, tester and cohort effects on data from these assays. We find strong evidence for the existence of two quantitative trait loci (i.e., genomic regions containing variability-causing genes), one for thermal nociception on mouse chromosome (Chr) 17 (Chr 17; Tpnr3) and one for formalin test nociception on mouse Chr 12 (Nociq3). We note, however, that the nociceptive assays in this battery feature strong main effects and interactions of sex, tester, and cohort, which if not controlled or covaried can seriously confound interpretation of genetic experiments, including the comparison of transgenic knockout mice to their wild-type controls.