奖励系统连接的多巴胺能调节是偏头痛疼痛和情绪痛苦的基础,Journal of Pain Research

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奖励系统连接的多巴胺能调节是偏头痛疼痛和情绪痛苦的基础
Journal of Pain Research ( IF 2.5 ) Pub Date : 2021-03-09 , DOI: 10.2147/jpr.s296540
Dajung J Kim ₁ , Hassan Jassar ₁ , Manyoel Lim ₁ , Thiago D Nascimento ₁ , Alexandre F DaSilva ₁

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目的：有人提出奖励系统功能障碍可能是偏头痛中情绪和疼痛的原因。然而，缺乏证据表明改变的奖赏系统连接是否与临床表现直接相关，包括负面影响和发作期疼痛的严重程度，以及在分子水平上，多巴胺 (DA) D2/D3 受体 (D2/3Rs) 信号传导参与编码动机和情感线索。
患者和方法：我们从发作间期发作性偏头痛 (EM) 患者和年龄匹配的健康对照中获取静息状态功能 MRI，以及正电子发射断层扫描 (PET) [ ¹¹C]raclopride，一种用于 DA D2/3Rs 的选择性放射性示踪剂，来自这些参与者的一个子集。伏隔核 (NAc) 被播种以测量功能连接性 (FC) 和 DA D2/3Rs 可用性，基于其与疼痛相关的厌恶/奖励功能的基本参与。还评估了大脑测量与正面/负面影响和发作期疼痛严重程度的关联。
结果：与对照组相比，EM组与疼痛和情绪调节相关区域的右侧NAc连接性较弱，如杏仁核、前扣带回皮层、海马和丘脑；但显示出与背外侧前额叶皮层和舌回更强的左侧 NAc 连接。此外，在改变的 NAc 连接中，只有右 NAc-杏仁核连接与偏头痛患者的 DA D2/3Rs 可用性呈负相关（诊断组与 D2/3Rs 相互作用 p < 0.007）。在临床水平上，这种较弱的 NAc-杏仁核连接性与较低的发作间期积极影响和较大的发作期疼痛严重程度有关，在头部和面部扩展区域（疼痛区域和强度数总和，PAINS）。
结论：总之，我们的研究结果表明，改变的奖励系统连接，特别是 NAc 和杏仁核之间的连接，可能会受到内源性 DA D2/3Rs 信号传导的影响，并且这种过程可能是一种神经机制，是发作性偏头痛患者情绪和疼痛的基础。

关键词：多巴胺，伏隔核，功能连接，偏头痛，奖赏系统，颅面痛

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Dopaminergic Regulation of Reward System Connectivity Underpins Pain and Emotional Suffering in Migraine

Purpose: It has been suggested that reward system dysfunction may account for emotion and pain suffering in migraine. However, there is a lack of evidence whether the altered reward system connectivity is directly associated with clinical manifestations, including negative affect and ictal pain severity and, at the molecular level, the dopamine (DA) D2/D3 receptors (D2/3Rs) signaling implicated in encoding motivational and emotional cues.
Patients and Methods: We acquired resting-state functional MRI from interictal episodic migraine (EM) patients and age-matched healthy controls, as well as positron emission tomography (PET) with [¹¹C]raclopride, a selective radiotracer for DA D2/3Rs, from a subset of these participants. The nucleus accumbens (NAc) was seeded to measure functional connectivity (FC) and DA D2/3Rs availability based on its essential involvement in pain-related aversive/reward functions. Associations of the brain measures with positive/negative affect and ictal pain severity were also assessed.
Results: Compared with controls, the EM group showed weaker right NAc connectivity with areas implicated in pain and emotional regulation, such as the amygdala, rostral anterior cingulate cortex, hippocampus, and thalamus; but showed stronger left NAc connectivity with the dorsolateral prefrontal cortex and lingual gyrus. Moreover, among the altered NAc connectivities, only right NAc-amygdala connectivity was inversely correlated with DA D2/3Rs availability in migraine patients (diagnostic group-by-D2/3Rs interaction p < 0.007). At a clinical level, such weaker NAc-amygdala connectivity was associated with lower interictal positive affect and greater ictal pain severity over the head and facial extension area (pain area and intensity number summation, PAINS).
Conclusion: Together, our findings suggest that altered reward system connectivity, specifically between the NAc and amygdala, might be affected by endogenous DA D2/3Rs signaling, and such process might be a neural mechanism that underlies emotional and pain suffering in episodic migraineurs.

Keywords: dopamine, nucleus accumbens, functional connectivity, migraine, reward system, craniofacial pain

更新日期：2021-04-20

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