一項發(fā)表在12月20日PLOS Genetics雜志上的研究帶來了更多證據(jù)表明,，特定基因與慢性疼痛相關,，并強調參與慢性疼痛發(fā)生的這條途徑是潛在更有效進行緩解疼痛治療的手段,。
倫敦大學國王學院,、輝瑞制藥有限公司和北京華大基因研究院（BGI）合作研究采用了一種新的方法來研究和比較DNA,，又稱“外顯子組測序”,，以確定疼痛敏感性有關的遺傳變異。
主要作者Frances Williams博士說：慢性疼痛是一種重要的個人和社會經(jīng)濟負擔,，有近五分之一的人在某一段時間內會經(jīng)歷慢性疼痛,。
目前,，疼痛治療往往療效有限或存在副作用,，對許多人來說，一種新的方法來緩解疼痛可能性是一個令人興奮的科技成果,。據(jù)了解,，那些日常生活中對疼痛最敏感的人更容易發(fā)展為慢性疼痛。
為了識別人對疼痛的靈敏度水平,，研究人員測試了2500名志愿者,，在他們手臂上使用加熱探頭,。當他們感受到痛時，志愿者被要求按下一個按鈕,，這使得科學家們能夠確定個人的疼痛閾值,。然后外顯子組測序用來分析對痛最敏感的200人和疼痛最不敏感的200人的DNA。
項目經(jīng)理Xin Jin說：越來越多的證據(jù)支持我們的理論,，在全基因組關聯(lián)研究中，罕見的基因變異被忽略了其在復雜疾病和性狀的重要作用,。下一代測序將有可能探索這些罕見的變異,，找出不同疼痛敏感個體之間的遺傳變異,。（生物谷：Bioon.com）
doi:10.1371/journal.pgen.1003095
PMC:
PMID:
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.
