Genetic and sex influence on neuropathic pain-like behaviour after spinal cord injury in the rat
Article first published online: 4 APR 2012
© 2012 European Federation of International Association for the Study of Pain Chapters
European Journal of Pain
Volume 16, Issue 10, pages 1368–1377, November 2012
How to Cite
Dominguez, C.A., Ström, M., Gao, T., Zhang, L., Olsson, T., Wiesenfeld-Hallin, Z., Xu, X.-J. and Piehl, F. (2012), Genetic and sex influence on neuropathic pain-like behaviour after spinal cord injury in the rat. European Journal of Pain, 16: 1368–1377. doi: 10.1002/j.1532-2149.2012.00144.x
This work was supported by the Swedish Brain Foundation, the Swedish Association of Persons with Neurological Disabilities and the Swedish Research Council.
Conflicts of interest
- Issue published online: 4 OCT 2012
- Article first published online: 4 APR 2012
- Manuscript Accepted: 7 MAR 2012
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)-RT1av1 strain in a model of photochemically induced SCI.
In this study, a genome-wide linkage study in an F2 cross between the susceptible DA and resistant PVG-RT1av1 strains was performed in order to explore the influence of genes and sex for SCI pain.
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.
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.