近五分之一的人患有慢性疼痛,，慢性疼痛是指持續(xù)一個月以上（以前為三個月或半年）的疼痛，也有人把慢性疼痛比喻為一種不死的癌癥。目前，中國至少有一億以上的慢性疼痛患者。
在過去二十年中,，對于慢性痛苦的了生物學(xué)研究獲得的了許多突破，但問題仍很多,。治療慢性疼痛的一個主要挑戰(zhàn)就是要弄清楚為什么某些人會患慢性疼痛,。弄清楚這一點(diǎn)有助于制定特定患者人群的個性化治療策略。
研究結(jié)果發(fā)表在《自然醫(yī)學(xué)》雜志上,。蒙特利爾的麥吉爾大學(xué)教授Jeffrey Mogil和多倫多大學(xué)附屬醫(yī)院的Michael Salter教授領(lǐng)導(dǎo)的研究小組確定了影響慢性疼痛敏感性的一個重要基因,。研究結(jié)果還表明一種個性化治療慢性疼痛的新方法。
研究人員發(fā)現(xiàn)編碼疼痛受體的基因是P2X7受體,。具體來說,，科學(xué)家發(fā)現(xiàn)P2X7中一個單一氨基酸的變化控制引起慢性疼痛的兩個主要原因的靈敏度：炎癥和神經(jīng)損傷。
眾所周知,，氨基酸的變化只會影響P2X7受體形成的毛孔讓大型分子通過的功能,，但不影響該受體其他功能，這一點(diǎn)允許多離子通過,。使用靶向作用于孔隙形成的一種肽,，研究人員發(fā)現(xiàn)疼痛會大大減少,。
然后科學(xué)家研究了兩種不同類型的持續(xù)性疼痛患者之間的遺傳差異：慢性乳房切除手術(shù)后疼痛和骨關(guān)節(jié)炎。在這兩種情況下他們發(fā)現(xiàn),，P2X7受體基因遺傳變異后孔隙形成率較低的人,，疼痛程度較低。
麥吉爾大學(xué)疼痛研究員Mogil, E.P. Taylor教授說：“我們的研究結(jié)果表明有可能開發(fā)出一種藥物能阻塞這個關(guān)鍵受體的毛孔,，而不影響該受體的其他功能，從而發(fā)揮止痛作用,，同時盡量減少副作用,。
Salter、Anne教授和SickKids的Tanenbaum分子醫(yī)學(xué)主席Max表示：這些發(fā)現(xiàn)有助于慢性疼痛個體化治療的發(fā)展,。美國和以色列的科學(xué)家們也參與這項(xiàng)研究,。
這項(xiàng)研究是由Krembil基金會、路易絲和艾倫·愛德華茲基金會,、美國國立衛(wèi)生研究院（NIH）加拿大健康研究所（CIHR）和SickKids基金會研究院資助,。（生物谷：Bioon）
doi:10.1038/nm.2710
PMC:
PMID:
Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity
Robert E Sorge, Tuan Trang, Ruslan Dorfman, Shad B Smith, Simon Beggs, Jennifer Ritchie, Jean-Sebastien Austin, Dmitri V Zaykin, Heather Vander Meulen, Michael Costigan, Teri A Herbert, Merav Yarkoni-Abitbul, David Tichauer, Jessica Livneh, Edith Gershon, Ming Zheng, Keith Tan, Sally L John, Gary D Slade, Joanne Jordan, Clifford J Woolf, Gary Peltz, William Maixner, Luda Diatchenko, Ze'ev Seltzer, Michael W Salter, Jeffrey S Mogil.
Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary1. Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da2, 3. Using genome-wide linkage analyses, we discovered an association between nerve-injury–induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain.
