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. CONCLUSION: 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.
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. CONCLUSION: 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: Dou Yu; Devang K Thakor; Inbo Han; Alexander E Ropper; Hariprakash Haragopal; Richard L Sidman; Ross Zafonte; Steven C Schachter; Yang D Teng Journal: Proc Natl Acad Sci U S A Date: 2013-02-05 Impact factor: 11.205
Authors: Gary H Blumenthal; Bharadwaj Nandakumar; Ashley K Schnider; Megan R Detloff; Jerome Ricard; John R Bethea; Karen A Moxon Journal: Eur J Pain Date: 2021-01-25 Impact factor: 3.931
Authors: Cecilia A Dominguez; Karl E Carlström; Xing-Mei Zhang; Faiez Al Nimer; Rickard P F Lindblom; Andre Ortlieb Guerreiro-Cacais; Fredrik Piehl Journal: Mol Pain Date: 2014-12-10 Impact factor: 3.395