Identification of quantitative trait loci for chemical/inflammatory nociception in mice.
Sensitivity to pain is widely variable, and much of this variability is genetic in origin. The specific genes responsible have begun to be identified, but only for thermal nociception. In order to facilitate the identification of polymorphic, pain-related genes with more clinical relevance, we performed quantitative trait locus (QTL) mapping studies of the most common assay of inflammatory nociception, the formalin test. QTL mapping is a technique that exploits naturally occurring variability among inbred strains for the identification of genomic locations containing genes contributing to that variability. An F2 intercross was constructed using inbred A/J and C57BL/6J mice as progenitors, strains previously shown to display resistance and sensitivity, respectively, to formalin-induced nociception. Following phenotypic testing (5% formalin, 25 microl intraplantar injection), mice were genotyped at 90 microsatellite markers spanning the genome. We provide evidence for two statistically significant formalin test QTLs - chromosomal regions whose inheritance is associated with trait variability - on distal mouse chromosomes 9 and 10. Identification of the genes underlying these QTLs may illuminate the basis of individual differences in inflammatory pain, and lead to novel analgesic treatment strategies.
Wilson
Sonya G
SG
Department of Psychology and Neuroscience Program, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA Department of Behavioral Neuroscience and VA Medical Center, Oregon Health Sciences University, Portland, OR 97201, USA Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Chesler
Elissa J
EJ
Hain
Heather
H
Rankin
Andrew J
AJ
Schwarz
Joel Z
JZ
Call
Stanford B
SB
Murray
Michael R
MR
West
Erin E
EE
Teuscher
Cory
C
Rodriguez-Zas
Sandra
S
Belknap
John K
JK
Mogil
Jeffrey S
JS
D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes; D004777:Environment; D005260:Female; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D020078:Neurogenic Inflammation / Q000235:genetics; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000235:genetics*; D010147:Pain Measurement; D019655:Quantitative Trait, Heritable; D013045:Species Specificity