IDENTIFICATION OF A SEX-SPECIFIC QUANTITATIVE TRAIT LOCUS MEDIATING NONOPIOID STRESS-INDUCED ANALGESIA IN FEMALE MICE

It is increasingly appreciated that the sexes differ in their percepti on of noxious stimuli and in their responsivity to exogenous and endog enous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopio id (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produce d by forced swims and suggested that female mice possess a sex-specifi c SIA mechanism. This female-specific system is now known to be estrog en-dependent, to be ontogenetically organized, and to vary with reprod uctive status; however, its neurochemical identity remains obscure. in an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experi ment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F-2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min a fter cessation of the swim. We report the localization of a QTL statis tically associated with SIA magnitude [p = 0.00000012; logarithm of th e odds (LOD) = 6.1] in female mice only. This female-specific QTL, whi ch we name Fsia1, is located on chromosome 8 at 52-84 cM from the cent romere and accounts far 17-26% of the overall trait variance in this s ex. The present data provide further evidence of the existence of a fe male-specific SIA mechanism and highlight the important role of both g enetic background and gender in the inhibition of pain.