1 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Mol Pain. 2018 Jan-Dec;14:1744806918763275. doi: 10.1177/1744806918763275. Epub 2018 Feb 15.
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.
Nav1.8 的表达受 SCN10A 编码的影响，可影响疼痛传递，从而调节人类的疼痛表型。在本研究中，我们评估了位于 SCN10A 增强子区域的变体 rs6801957 是否可能影响人类疼痛。通过 293T 细胞中的双荧光素酶报告基因分析，我们发现 SCN10A 增强子 A（Enh-A）增加了 SCN10A 启动子的活性（P<0.05）。此外，在 309 名健康女性的队列中，发现突变 rs6801957 A/A 与人类实验性机械性疼痛敏感性降低显著相关（P<0.05）。我们发现突变基因型 A/A 与野生型 G/G 相比，抑制了 Enh-A 的增强效应（P<0.05）。rs6801957 与人类实验性机械性疼痛敏感性之间的关联在更大的 1005 名女性队列中得到了进一步验证（P<0.05）。总之，这些结果表明，变体 rs6801957 和 Enh-A 可能影响 SCN10A 基因表达，在人类机械性疼痛敏感性中发挥重要作用。
