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Publication : Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice.

First Author  Mogil JS Year  1997
Journal  J Neurosci Volume  17
Issue  20 Pages  7995-8002
PubMed ID  9315917 Mgi Jnum  J:43467
Mgi Id  MGI:1097768 Doi  10.1523/JNEUROSCI.17-20-07995.1997
Citation  Mogil JS, et al. (1997) Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice. J Neurosci 17(20):7995-8002
abstractText  It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive 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 experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 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 after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.
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