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 (IP) acetic acid test and genome-wide quantitative trait locus (QTL) mapping was performed on the mean number of abdominal contraction and extension movements in three distinct groups of BXD RI mouse strains in two separate experiments. Combined mapping results detected two 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 IP 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.

HTR7 Mediates Serotonergic Acute and Chronic Itch

“…Previous studies have shown that genetically distinct inbred mouse strains display variable somatosensory behaviors such as pain and itch (Green et al, 2006; Nair et al, 2011). We set out to identify transcripts that were co-regulated with itch behaviors across such mouse strains.…”

Genetic and sex influence on neuropathic pain‐like behaviour after spinal cord injury in the rat

“…In addition, a clear influence of sex is demonstrated, however, not being directly linked to a genetic effect mapping to the sex chromosomes. The present study lays the basis for further studies to dissect the genetic contribution to pain after SCI injury, as has been performed in peripheral nerve injury models (Costigan et al., ; Fortin et al., ; Nissenbaum et al., ; Nair et al., ). One strategy for identifying candidate genes and pathway regulated by the identified regions is to use expression QTL mapping using microarrays as has been successfully performed in other traits (Pravenec et al., ).…”

“…This QTL is between 26.10 and 48.24 Mb and is not overlapping with any of our newly detected QTLs. From the table, there is only one QTL in mice on chromosome 3 (54.93–60.47 Mb) (Nair et al., ) that is in synteny with our QTL on rat chromosome 2 (144.34–149.86 Mb). However, the lack of overlap is not surprising in view of our previous finding of genetically different regulation of pain induced by injury to the peripheral and CNSs (Dominguez et al., ,b).…”

“…Strain differences in pain sensitivity are well documented in the literature and enable whole genome QTL mapping to dissect the genetic regulation of pain. So far, this has been performed in different models of peripheral nerve injury‐induced pain/pain behaviour, leading to the identification of gene regions, mainly in mice, regulating inflammatory nociception, autotomy, thermal nociception and capsaicin sensitivity (Seltzer et al., ; Wilson et al., ; Furuse et al., ; Devor et al., , ; Nissenbaum et al., , ; Smith et al., ; Fortin et al., ; Nair et al., ). The QTLs detected, to the best of our knowledge, so far are listed in Table , as well as their syntenic regions.…”

Genetic variability to diet-induced hippocampal dysfunction in BXD recombinant inbred (RI) mouse strains

“…Statistical significance was defined at P <0.05. Heritability was determined as h 2 = VA/(VA + VE), where VA is the additive genetic variation estimated by the between-strain variance and VE is the environmental variance estimated by the within-strain variance from the ANOVA results [34]. …”