一项发表在12月20日PLOS Genetics杂志上的研究带来了更多证据表明，特定基因与慢性疼痛相关，并强调参与慢性疼痛发生的这条途径是潜在更有效进行缓解疼痛治疗的手段。
伦敦大学国王学院、辉瑞制药有限公司和北京华大基因研究院（BGI）合作研究采用了一种新的方法来研究和比较DNA，又称“外显子组测序”，以确定疼痛敏感性有关的遗传变异。
主要作者Frances Williams博士说：慢性疼痛是一种重要的个人和社会经济负担，有近五分之一的人在某一段时间内会经历慢性疼痛。
目前，疼痛治疗往往疗效有限或存在副作用，对许多人来说，一种新的方法来缓解疼痛可能性是一个令人兴奋的科技成果。据了解，那些日常生活中对疼痛最敏感的人更容易发展为慢性疼痛。
为了识别人对疼痛的灵敏度水平，研究人员测试了2500名志愿者，在他们手臂上使用加热探头。当他们感受到痛时，志愿者被要求按下一个按钮，这使得科学家们能够确定个人的疼痛阈值。然后外显子组测序用来分析对痛最敏感的200人和疼痛最不敏感的200人的DNA。
项目经理Xin Jin说：越来越多的证据支持我们的理论，在全基因组关联研究中，罕见的基因变异被忽略了其在复杂疾病和性状的重要作用。下一代测序将有可能探索这些罕见的变异，找出不同疼痛敏感个体之间的遗传变异。（生物谷：Bioon.com）
doi:10.1371/journal.pgen.1003095
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Genes Contributing to Pain Sensitivity in the Normal Population: An Exome Sequencing Study.
Frances M. K. Williams, Serena Scollen, Dandan Cao, Yasin Memari, Craig L. Hyde, Baohong Zhang, Benjamin Sidders, Daniel Ziemek, Yujian Shi, Juliette Harris, Ian Harrow, Brian Dougherty, Anders Malarstig, Robert McEwen, Joel C. Stephens, Ketan Patel, Cristina Menni, So-Youn Shin, Dylan Hodgkiss, Gabriela Surdulescu, Wen He, Xin Jin, Stephen B. McMahon, Nicole Soranzo, Sally John, Jun Wang, Tim D. Spector.
Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to search for rare gene variants (MAF<5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. Thus in TUK1, 101 pain-sensitive and 102 pain-insensitive were examined, while in TUK2 there were 114 and 96 individuals respectively. A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10?4). This pathway is already implicated in animal models and human studies of pain, supporting the notion that it may provide fruitful new targets in pain management. The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits.
