BRAIN IMAGING AND PAIN: ANALYSIS OF PLACEBO ANALGESIA

描述(申请人提供)：该项目旨在研究安慰剂止痛的神经机制。将采用一种创新的安慰剂方案，评估安慰剂对内脏和皮肤疼痛刺激的反应。功能磁共振成像(FMRI)将能够描述临床人群中参与安慰剂止痛的大脑机制，这些临床人群将内脏疼痛作为临床综合征的一部分。该项目将利用以前对肠易激综合征(IBS)患者所做的工作，在这些患者中，内脏和皮肤疼痛刺激显示出不同的大脑激活。在同样的人群中，已经证明了对特定预期反应集的强大和可靠的安慰剂反应。拟议的项目将结合这些方案来获得IBS受试者在自然病史、安慰剂和活性物质(直肠利多卡因)条件下的脑图像。预计结果将显示，安慰剂反应将选择性地激活特定的大脑区域。与安慰剂条件相比，在自然历史条件下，以下大脑区域的神经活动(根据rCBF测量)将更强：-外侧和/或内侧丘脑、躯体感觉区1和2、岛叶皮质、前扣带回皮质(ACC)、后扣带回皮质(PCC)和前额叶皮质。此外，安慰剂机制主要是通过在较低的神经系统水平(脊髓)减弱伤害性信号来发挥作用的，其证据将是丘脑、躯体感觉、ACC和PCC的激活减少。先前的研究表明，对止痛的预期和渴望将显著预测安慰剂的止痛效果。预计这些措施也将与上述大脑激活模式相关联。通过比较安慰剂条件和直肠利多卡因条件，大脑和中枢神经系统相关机制与外周(受体部位)相关机制将被区分开来。

DESCRIPTION (provided by applicant): This project is designed to investigate the neural mechanisms of placebo analgesia. An innovative placebo protocol that assesses the placebo response to both visceral and cutaneous pain stimulation will be employed. Functional Magnetic Resonance Imaging (fMRI) will enable the characterization of brain mechanisms involved in placebo analgesia in a clinical population which experiences visceral pain as part of their clinical syndrome. This project will capitalize on previous work with Irritable Bowel Syndrome (IBS) patients where differential brain activation was demonstrated to visceral and cutaneous pain stimuli. In this same population a powerful and reliable placebo response to specific expectancy response sets has been demonstrated. The proposed project will combine these protocols to obtain brain images of IBS subject during natural history, placebo, and active agent (rectal lidocaine) conditions. It is anticipated that results will show that the placebo response will selectively activate specific brain regions. Neural activity (as measured by rCBF) will be greater in natural history conditions as compared to placebo conditions in the following brain regions: - lateral and/or medial thalamus, somatosensory areas 1 and 2, insular cortex, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and prefrontal cortex. Furthermore, placebo mechanisms that operate primarily through attenuation of nociceptive signals at lower nervous system levels (spinal cord) will be evidenced by decreased thalamic, somatosensory, ACC, and PCC activation. Previous research indicates that expectancy and desire for pain relief will significantly predict the pain reduction from placebo. It is anticipated that these measures will also be associated with the above described brain activation patterns. By comparing the placebo conditions to the rectal lidocaine condition, brain and central nervous system related mechanisms versus peripheral (receptor site) related mechanisms will be differentiated.