The Effect of SCN9A Variation on Basal Pain Sensitivity in the General Population: An Experimental Study in Young Women

Duan, Guangyou; Guo, Shanna; Zhang, Yuhao; Ying, Ying; Huang, Ping; Wang, Qingli; Zhang, Li; Zhang, Xianwei

doi:10.1016/j.jpain.2015.06.011

Cited by 25 publications

(24 citation statements)

References 45 publications

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“…Withdrawal latency time (WLT) was measured to evaluate heat pain sensitivity. 19 For the larger population of 1025 women, who all were scheduled for elective gynaecological surgery, experimental pain tests were performed in the gynaecology ward prior to surgery. For this population, only mechanical pain sensitivity, including D-PPT, D-PTO, S-PPT and S-PTO, were analysed, and the test procedure was same as that in the primary study.…”

Section: Methodsmentioning

confidence: 99%

A variant in the SCN10A enhancer may affect human mechanical pain sensitivity

et al. 2018

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Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assays in 293T cells, we found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A promoter (P < 0.05). Additionally, in a cohort of 309 healthy women, mutant rs6801957 A/A was found to have a significant association with decreased human experimental mechanical pain sensitivity (P < 0.05). We then found that mutant genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G (P < 0.05). The association between rs6801957 and human experimental mechanical pain sensitivity was further validated in a larger cohort of 1005 women (P < 0.05). In conclusion, these results demonstrated that the variant rs6801957 and Enh-A may affect SCN10A gene expression and play an important role in human mechanical pain sensitivity.

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Section: Methodsmentioning

confidence: 99%

A variant in the SCN10A enhancer may affect human mechanical pain sensitivity

et al. 2018

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“…After whole-genome genotyping, data were analyzed using GenomeStudio Genotyping module v1.6.3 (Illumina) to evaluate the quality of results, and genotype data for SNPs with SCN9A and SCN10A gene annotations were extracted. The analyzed SNPs were SCN9As (rs7607967, rs12994338, and rs13017637) and SCN10A (rs12632942 and rs6795970), which were evaluated in previous reports [17,[22][23][24][25].…”

Section: Genotypingmentioning

confidence: 99%

Taxane-induced sensory peripheral neuropathy is associated with an SCN9A single nucleotide polymorphism in Japanese patients

Tanabe¹,

Shiraishi²,

Hashimoto³

et al. 2020

BMC Cancer

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Background: Sodium channels located in the dorsal root ganglion, particularly Nav1.7 and Nav1.8, encoded by SCN9A and SCN10A, respectively, act as molecular gatekeepers for pain detection. Our aim was to determine the association between TIPN and SCN9A and SCN10A polymorphisms. Methods: Three single nucleotide polymorphisms (SNPs) in SCN9A and two in SCN10A were investigated using wholegenome genotyping data from 186 Japanese breast or ovarian cancer patients classified into two groups as follows: cases that developed taxane-induced grade 2-3 neuropathy (N = 108) and controls (N = 78) with grade 0-1 neuropathy. Multiple logistic regression analyses were conducted to evaluate associations between TIPN and SNP genotypes. Results: SCN9A-rs13017637 was a significant predictor of grade 2 or higher TIPN (odds ratio (OR) = 3.463; P = 0.0050) after correction for multiple comparisons, and precision was improved when only breast cancer patients were included (OR 5.053, P = 0.0029). Moreover, rs13017637 was a significant predictor of grade 2 or higher TIPN 1 year after treatment (OR 3.906, P = 0.037), indicating its contribution to TIPN duration. Conclusion: SCN9A rs13017637 was associated with the severity and duration of TIPN. These findings are highly exploratory and require replication and validation prior to any consideration of clinical use.

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“…Similar findings have been reported for SCN9A (encoding Nav1.7), whose mutations may lead to congenital insensitivity or extreme sensitivity to pain. [ 12 – 15 ] Based on our previous findings that single-nucleotide polymorphisms (SNPs) in SCN9A (encoding Nav1.7) can affect basal and postoperative pain sensitivity, [ 16 – 18 ] we speculated that there may also be an association between SCN11A and pain sensitivity.…”

Section: Introductionmentioning

confidence: 99%