Molecular and Behavioral Neuroscience Institute, and Departments of Psychiatry, Anesthesiology, Obstetrics and Gynecology, and Radiology, University of Michigan, Ann Arbor, Michigan 48109, Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48104, Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, and School of Dentistry, University of Maryland, Baltimore, Maryland 21201.
J Neurosci. 2013 Sep 11;33(37):14729-37. doi: 10.1523/JNEUROSCI.1400-13.2013.
The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional μ-opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. We compared μ-opioid receptor availability in vivo at baseline, during pain expectation, and with moderate levels of sustained pain in 16 patients with chronic nonspecific back pain (CNBP) and in 16 age- and gender-matched healthy control subjects, using the μ-opioid receptor-selective radioligand [(11)C]carfentanil and positron emission tomography. We found that CNBP patients showed baseline increases in thalamic μ-opioid receptor availability, contrary to a previously studied sample of patients diagnosed with fibromyalgia. During both pain expectation and sustained pain challenges, CNBP patients showed regional reductions in the capacity to activate this neurotransmitter system compared with their control sample, further associated with clinical pain and affective state ratings. Our results demonstrate heterogeneity in endogenous opioid system functional measures across pain conditions, and alterations in both receptor availability and endogenous opioid function in CNBP that are relevant to the clinical presentation of these patients and the effects of opioid analgesics on μ-opioid receptors.
许多慢性疼痛综合征中缺乏一致的终末器官异常,这促使人们寻找适应性中枢神经系统机制,以解释其临床表现和病程。在这里,我们研究了大脑区域μ-阿片受体介导的神经传递在人类慢性背痛中的作用,这是疼痛调节的最佳机制之一。我们比较了 16 名慢性非特异性背痛(CNBP)患者和 16 名年龄和性别匹配的健康对照者在基线、疼痛预期和中等程度持续疼痛期间体内μ-阿片受体的可用性,使用μ-阿片受体选择性放射性配体[11C]carfentanil 和正电子发射断层扫描。我们发现,CNBP 患者的丘脑μ-阿片受体可用性在基线时增加,这与先前研究的纤维肌痛患者样本相反。在疼痛预期和持续疼痛挑战期间,CNBP 患者与对照组相比,该神经递质系统的激活能力出现区域性下降,这与临床疼痛和情感状态评分进一步相关。我们的研究结果表明,疼痛状态下内源性阿片系统功能测量存在异质性,CNBP 患者的受体可用性和内源性阿片功能发生改变,与这些患者的临床表现和阿片类镇痛药对μ-阿片受体的影响有关。