Bräscher Anne-Kathrin, Becker Susanne, Hoeppli Marie-Eve, Schweinhardt Petra
Alan Edwards Centre for Research on Pain, Faculty of Dentistry, McGill University, Montreal, Quebec H3A 1G1, Canada, Department of Clinical Psychology, Psychotherapy and Experimental Psychopathology, Johannes Gutenberg University Mainz, Mainz 55122, Germany,
Alan Edwards Centre for Research on Pain, Faculty of Dentistry, McGill University, Montreal, Quebec H3A 1G1, Canada, Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Mannheim 68159, Germany.
J Neurosci. 2016 May 4;36(18):5013-25. doi: 10.1523/JNEUROSCI.1954-15.2016.
Uncontrollable, compared with controllable, painful stimulation can lead to increased pain perception and activation in pain-processing brain regions, but it is currently unknown which brain areas mediate this effect. When pain is controllable, the lateral prefrontal cortex (PFC) seems to inhibit pain processing, although it is unclear how this is achieved. Using fMRI in healthy volunteers, we examined brain activation during controllable and uncontrollable stimulation to answer these questions. In the controllable task, participants self-adjusted temperatures applied to their hand of pain or warm intensities to provoke a constant sensation. In the uncontrollable task, the temperature time courses of the controllable task were replayed (yoked control) and participants rated their sensation continuously. During controllable pain trials, participants significantly downregulated the temperature to keep their sensation constant. Despite receiving the identical nociceptive input, intensity ratings increased during the uncontrollable pain trials. This additional sensitization was mirrored in increased activation of pain-processing regions such as insula, anterior cingulate cortex, and thalamus. Further, increased connectivity between the anterior insula and medial PFC (mPFC) in the uncontrollable and increased negative connectivity between dorsolateral PFC (dlPFC) and insula in the controllable task were observed. This suggests a pain-facilitating role of the mPFC during uncontrollable pain and a pain-inhibiting role of the dlPFC during controllable pain, both exerting their respective effects via the anterior insula. These results elucidate neural mechanisms of context-dependent pain modulation and their relation to subjective perception.
Pain control is of uttermost importance and stimulus controllability is an important way to achieve endogenous pain modulation. Here, we show differential effects of controllability and uncontrollability on pain perception and cerebral pain processing. When pain was controllable, the dorsolateral prefrontal cortex downregulated pain-evoked activation in important pain-processing regions. In contrast, sensitization during uncontrollable pain was mediated by increased connectivity of the medial prefrontal cortex with the anterior insula and other pain-processing regions. These novel insights into cerebral pain modulation by stimulus controllability have the potential to improve treatment approaches in pain patients.
与可控性疼痛刺激相比，不可控性疼痛刺激会导致疼痛感知增强以及疼痛处理脑区的激活，但目前尚不清楚哪些脑区介导了这种效应。当疼痛可控时，外侧前额叶皮质（PFC）似乎会抑制疼痛处理，尽管尚不清楚其具体实现方式。我们利用功能磁共振成像（fMRI）对健康志愿者进行研究，观察在可控性和不可控性刺激过程中的脑激活情况，以回答这些问题。在可控性任务中，参与者自行调整施加于手部的疼痛或温热强度的温度，以引发持续的感觉。在不可控性任务中，回放可控性任务的温度时间进程（匹配对照），参与者持续对自己的感觉进行评分。在可控性疼痛试验期间，参与者显著下调温度以保持感觉恒定。尽管接受了相同的伤害性输入，但在不可控性疼痛试验期间，强度评分增加。这种额外的敏感化反映在诸如脑岛、前扣带回皮质和丘脑等疼痛处理区域的激活增加上。此外，在不可控性试验中观察到前脑岛与内侧前额叶皮质（mPFC）之间的连接增加，而在可控性任务中背外侧前额叶皮质（dlPFC）与脑岛之间的负连接增加。这表明内侧前额叶皮质在不可控性疼痛期间具有促进疼痛的作用，而背外侧前额叶皮质在可控性疼痛期间具有抑制疼痛的作用，两者均通过前脑岛发挥各自的效应。这些结果阐明了情境依赖性疼痛调制的神经机制及其与主观感知的关系。
疼痛控制至关重要，刺激可控性是实现内源性疼痛调制的重要方式。在此，我们展示了可控性和不可控性对疼痛感知和脑疼痛处理的不同影响。当疼痛可控时，背外侧前额叶皮质下调重要疼痛处理区域中由疼痛诱发的激活。相反，不可控性疼痛期间的敏感化是由内侧前额叶皮质与前脑岛及其他疼痛处理区域之间连接增加所介导的。这些关于刺激可控性对脑疼痛调制的新见解有可能改善疼痛患者的治疗方法。
