title: Genetic and sex influence on neuropathic pain-like behaviour after spinal cord injury in the rat.
abstract: BACKGROUND
  Chronic pain of neuropathic nature after spinal cord injury (SCI) is common and its underlying mechanisms are poorly understood. Genes, as well as sex, have been implicated, but not thoroughly investigated in experimental genetic models for complex traits. We have previously found that inbred Dark-Agouti (DA) rats develop more severe SCI pain-like behaviour than a major histocompatibility complex-congenic Piebald Virol Glaxo (PVG)-RT1(av1)  strain in a model of photochemically induced SCI.
  
  
  METHODS
  In this study, a genome-wide linkage study in an F2 cross between the susceptible DA and resistant PVG-RT1(av1)  strains was performed in order to explore the influence of genes and sex for SCI pain.
  
  
  RESULTS
  A consistent finding was that female rats in parental, F1 and F2 generations displayed increased pain sensitivity at testing before injury and also developed mechanical hypersensitivity more rapidly and to a greater extent than male rats. In addition, we could identify three quantitative trait loci (QTLs) associated with pain-like behaviour: a sex-specific QTL on chromosome 2, one on chromosome 15 and on chromosome 6. Animals carrying DA alleles at each of these loci were more susceptible to development of mechanical hypersensitivity compared with rats with PVG alleles.
  
  
  CONCLUSIONS
  This is the first whole genome QTL mapping of neuropathic pain-like behaviour in a model of SCI. The results provide strong support for a significant genetic and sex component in development of pain after SCI and provide the basis for further genetic dissection and positional cloning of the underlying genes.
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. cecilia.dominguez@ki.se
authors.forename: C A
authors.initials: CA
authors.lastname: Dominguez
authors.forename: M
authors.initials: M
authors.lastname: Ström
authors.forename: T
authors.initials: T
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: Z
authors.initials: Z
authors.lastname: Wiesenfeld-Hallin
authors.forename: X-J
authors.initials: XJ
authors.lastname: Xu
authors.forename: F
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006930:Hyperalgesia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D017288:Pain Threshold; D040641:Quantitative Trait Loci; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013119:Spinal Cord Injuries / Q000150:complications / Q000235:genetics / Q000503:physiopathology