Biggs Emma E, Timmers Inge, Heathcote Lauren C, Tremblay-McGaw Alexandra G, Noel Melanie, Borsook David, Simons Laura E
Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Palo Alto, CA, United States.
Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.
Pain. 2025 Mar 1;166(3):527-538. doi: 10.1097/j.pain.0000000000003382. Epub 2024 Aug 21.
Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain. Data from 58 participants were included in study 1 (chronic pain n = 34, pain free n = 24, mean age = 16 years), and 39 participants were included in study 2 (chronic pain n = 26, pain free n = 13, mean age = 16 years). Both studies used a threat-safety learning paradigm with memory recall (≈1 month later). Participants completed structural and functional (resting-state) magnetic resonance imaging, salivary cortisol measurements, and self-report measures. Adolescents with pain and pain-free peers consistently recalled being more afraid of safety cues (CS-) and, during heightened stress at encoding (higher cortisol levels), also reported being more afraid of threat cues (CS+). However, no memory bias was present for the emotional response to an aversive stimulus (US; loud scream) or for the recall of pain intensity. Functional connectivity of the amygdala and hippocampus with memory circuits related to the degree of memory bias, but the specific connections varied between the studies, and we observed no relationship between memory bias and brain morphology. Our findings highlight the value of considering the interaction between implicit and explicit memory systems, contributing to a more comprehensive understanding of emotional memory biases in the context of chronic pain.
对疼痛相关信息的记忆偏差可能会导致慢性疼痛的产生和维持；然而，关于这些偏差何时（以及对谁）出现的证据并不一致。因此，我们研究了可能影响记忆偏差的神经、压力和心理因素，重点关注激发失能行为的记忆：疼痛感知、对威胁和安全线索的条件反应，以及对厌恶的无害刺激的反应。对患有和未患有慢性疼痛的青少年进行了两项研究。研究1纳入了58名参与者的数据（慢性疼痛组n = 34，无疼痛组n = 24，平均年龄 = 16岁），研究2纳入了39名参与者（慢性疼痛组n = 26，无疼痛组n = 13，平均年龄 = 16岁）。两项研究均采用带有记忆回忆的威胁-安全学习范式（约1个月后）。参与者完成了结构和功能（静息态）磁共振成像、唾液皮质醇测量以及自我报告测量。患有疼痛的青少年和无疼痛的同龄人一致回忆起更害怕安全线索（CS-），并且在编码时压力增加（皮质醇水平较高）时，也报告更害怕威胁线索（CS+）。然而，对于对厌恶刺激（US；大声尖叫）的情绪反应或疼痛强度的回忆，不存在记忆偏差。杏仁核和海马体与与记忆偏差程度相关的记忆回路的功能连接，但具体连接在两项研究之间有所不同，并且我们未观察到记忆偏差与脑形态之间的关系。我们的研究结果强调了考虑内隐和外显记忆系统之间相互作用的价值，有助于更全面地理解慢性疼痛背景下的情绪记忆偏差。
