Department of Anesthesia, School of Medicine, Stanford University, Palo Alto, CA, USA Department of Human Biology, School of Arts & Sciences, Stanford University, Palo Alto, CA, USA.
Pain. 2011 Aug;152(8):1803-1810. doi: 10.1016/j.pain.2011.03.028. Epub 2011 Apr 30.
Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.
慢性阿片类药物暴露已知会在动物身上产生神经可塑性变化;然而,尚不清楚在短时间内以镇痛剂量使用阿片类药物是否也能类似地改变人类的大脑结构。在这项纵向磁共振成像研究中,10 名慢性腰痛患者每天口服吗啡 1 个月。在吗啡给药期前后立即采集大脑的高分辨率解剖图像。使用基于张量的形态计量学对全脑的灰质体积进行评估,并对这些显著的区域变化与吗啡剂量进行独立测试。有 13 个区域的体积发生了显著变化,其中几个区域的变化程度与吗啡剂量相关。与剂量相关的体积减小主要发生在右侧杏仁核。与剂量相关的体积增加见于右侧下丘脑、左侧额下回、右侧腹后扣带和右侧桥脑尾侧。停止使用阿片类药物平均 4.7 个月后的随访扫描显示,许多阿片类药物引起的变化是持续存在的。在一项单独的研究中,9 名服用盲法安慰剂胶囊 6 周的患者在随访期间没有出现明显的形态变化。这些结果增加了越来越多的文献表明,阿片类药物暴露会导致奖励和情感处理回路的结构和功能变化。在人类中,新接触处方阿片类镇痛药时,形态变化迅速发生。需要进一步研究来确定那些阿片类药物引起的灰质变化对临床的影响。