據(jù)一項新的研究報道,，身體在損傷后對自然的、阻斷痛覺的阿片類物質(zhì)的依賴可能促成了慢性疼痛的出現(xiàn),。阻斷機體對阿片類的過度使用可能會阻止急性疼痛向慢性疼痛的轉(zhuǎn)變,。在損傷時，機體通過釋放阿片物質(zhì)來阻斷痛覺,，沒有這一過程,，在手術(shù)或其它創(chuàng)傷性損傷之后所經(jīng)歷的急性疼痛將會更為嚴重。沒有人知道慢性疼痛到底是如何產(chǎn)生的,，且沒有可供阻止慢性的治療存在,。為了探索阿片類物質(zhì)在慢性疼痛中的作用，Gregory Corder及其同事在小鼠的爪子中制造了炎癥,，讓疼痛樣行為在數(shù)天至數(shù)周中（在小鼠的天然阿片類物質(zhì)的幫助下）自然消退,，并接著給予小鼠阿片類受體阻滯劑。這些阿片類阻滯藥物復現(xiàn)了與疼痛相關(guān)的行為以及在這些小鼠脊髓中的疼痛神經(jīng)元的激活,，即使注射是在受傷之后長達6個月時,。進一步放大時，研究人員發(fā)現(xiàn)了一種叫做μ-阿片樣受體（MOR）的可介導長時間疼痛抑制的特別的阿片樣受體,。在患有慢性疼痛的小鼠中,，MOR似乎被卡在一個持續(xù)“打開”的狀態(tài)。令人驚訝的是,，當給予一種阿片類阻滯劑時,，這些小鼠表現(xiàn)出了如發(fā)抖和震顫等阿片類戒斷的經(jīng)典體征（類似于當停服阿片類藥物時在成癮者中所見的情形）。沒有接受阿片類阻滯劑以破壞自然鎮(zhèn)痛的小鼠不會表現(xiàn)出這一行為,。研究人員發(fā)現(xiàn),，阻斷MOR不但快速啟動了疼痛及疼痛的傳輸，而且還產(chǎn)生了一種在脊髓中發(fā)現(xiàn)的已知會促成成癮及慢性疼痛的關(guān)鍵性的蛋白質(zhì)——I型腺苷酸環(huán)化酶,?？傊@些結(jié)果提示,，盡管MOR可以在受傷后讓急性疼痛得到控制,，但它也能造成機體對其自身的阿片類物質(zhì)變得依賴，而這會促成慢性疼痛的形成,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Science DOI: 10.1126/science.1239403
Constitutive μ-Opioid Receptor Activity Leads to Long-Term Endogenous Analgesia and Dependence
G. Corder1, S. Doolen1, R. R. Donahue1, M. K. Winter2, B. L. Jutras3, Y. He4, X. Hu4, J. S. Wieskopf5, J. S. Mogil5, D. R. Storm6, Z. J. Wang4, K. E. McCarson2, B. K. Taylor1,*
Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced μ-opioid receptor (MOR) constitutive activity (MORCA) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3′,5′-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MORCA initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MORCA suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.
