title: Genomic loci and candidate genes underlying inflammatory nociception.
abstract: Heritable genetic factors contribute significantly to inflammatory nociception. To determine candidate genes underlying inflammatory nociception, the current study used a mouse model of abdominal inflammatory pain. BXD recombinant inbred (RI) mouse strains were administered the intraperitoneal acetic acid test, and genome-wide quantitative trait locus (QTL) mapping was performed on the mean number of abdominal contraction and extension movements in 3 distinct groups of BXD RI mouse strains in 2 separate experiments. Combined mapping results detected 2 QTLs on chromosomes (Chr) 3 and 10 across experiments and groups of mice; an additional sex-specific QTL was detected on Chr 16. The results replicate previous findings of a significant QTL, Nociq2, on distal Chr 10 for formalin-induced inflammatory nociception and will aid in identification of the underlying candidate genes. Comparisons of sensitivity to intraperitoneal acetic acid in BXD RI mouse strains with microarray mRNA transcript expression profiles in specific brain areas detected covarying expression of candidate genes that are also found in the detected QTL confidence intervals. The results indicate that common and distinct genetic mechanisms underlie heritable sensitivity to diverse inflammatory insults, and provide a discrete set of high-priority candidate genes to investigate further in rodents and human association studies. Novel genomic regions linked to inflammatory nociception were detected, a previously reported locus was confirmed, and high-priority candidate genes for inflammatory nociception and pain were identified.
authors.affiliation: University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA VA Medical Center and Oregon Health & Science University, Portland, OR, USA Washington State University, Pullman, WA, USA The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Harsha K
authors.initials: HK
authors.lastname: Nair
authors.forename: Heather
authors.initials: H
authors.lastname: Hain
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Quock
authors.forename: Vivek M
authors.initials: VM
authors.lastname: Philip
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: John K
authors.initials: JK
authors.lastname: Belknap
authors.forename: William R
authors.initials: WR
authors.lastname: Lariviere
mesh_terms: D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D016001:Confidence Intervals; D030541:Databases, Genetic; D005260:Female; D016678:Genome / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010146:Pain / Q000209:etiology / Q000235:genetics*; D058748:Pain Perception / Q000502:physiology; D040641:Quantitative Trait Loci / Q000235:genetics*; D013180:Sprains and Strains / Q000235:genetics
chemical_list: D019342:Acetic Acid