Memory for pain: neural processing and cognitive intervention strategies

疼痛是一种感觉和情感体验，对学习很重要，但很少有研究探索我们将痛苦经历本身作为一种目标来记忆的能力。了解疼痛记忆的潜在机制可以帮助我们理解和干预疼痛相关的疾病。事实上，这些障碍中的一些最近被描述为源于适应不良的疼痛。我提议进行一系列致力于这一系列研究的研究。这些研究将以两个主要目标为指导。第一个是研究疼痛工作记忆(即疼痛记忆的短期存储)中涉及的神经过程。这将使我了解疼痛记忆巩固的早期阶段--通过这个过程，短期记忆稳定为长期记忆。使用心理物理、电生理和脑刺激方法，我将研究在工作记忆中保留疼痛的神经机制，以及它们与非疼痛触摸的工作记忆重叠的程度。我将比较参与者在痛苦和非痛苦刺激辨别任务中的表现，这些任务要求他们在记忆中保留一个刺激，并将其与另一个进行比较，同时瞬时扰乱与触觉工作记忆有关的大脑区域。我的第二个目标是使用一种名为重新巩固干扰的记忆研究范式，来评估我们如何干扰已经稳定到长期记忆中的联想疼痛记忆。根据这一理论，记忆踪迹的重新激活会启动一个易受记忆干扰的窗口。具体地说，可能使用双负荷范式，在这种范式中，认知/行为任务招募的神经过程干扰了重新巩固记忆所需的过程，从而破坏了记忆轨迹的稳定。这为消除适应不良的疼痛记忆提供了一种潜在的机制。为了测试这种可能性，我将使用健康志愿者在线索条件反射过程中进行的短暂的、实验诱导的疼痛。在重新激活阶段，参与者将执行一项以感觉或情绪处理为目标的工作记忆任务，因为这两个过程是疼痛体验的基础。在最后阶段，我将测量对先前与疼痛配对的视觉暗示的唤醒反应，以确定干扰过程是否有效。这些研究将确定感觉或情绪处理对巩固疼痛记忆更重要，因此更成功地干扰疼痛记忆的重新巩固。此外，从长远来看，我希望将成功的干预措施应用于自发性临床疼痛。这将为临床疼痛样本中疼痛记忆的性质提供洞察，并指导这些人群中潜在的干预策略。我提议的研究将有助于我们从理论上理解疼痛记忆。重要的是，它将显示疼痛的工作记忆与触觉工作记忆有何不同或重叠，以及疼痛的感觉或情感表征在疼痛记忆中占主导地位。特别是，它可以阐明躯体感觉通路和情感大脑网络在持续性、非解决性疼痛条件下对疼痛记忆的贡献。了解这些过程可以洞察疼痛记忆痕迹的本质，以及为什么它们可能表现出对擦除的抵抗力。除了重大的理论贡献，我的研究还将对疼痛管理策略和非药理学临床干预具有重要意义。

Pain is a sensory and emotional experience that is important for learning, but, few studies have explored our ability to remember painful experiences as an objective in its own right. Understanding the mechanisms underlying memory for pain could help us understand and intervene in pain-related disorders. Some of these disorders, indeed, have been recently characterised as stemming from maladaptive pain.I am proposing a series of studies committed to this line of investigation. These studies will be guided by two main aims. The first is to investigate the neural processes involved inworking memory for pain (i.e. short-term storage of a pain memory). This will allow me to understand the early stages of pain memory consolidation-the process by which short-term memory is stabilised into long-term memory. Using psychophysical, electrophysiological and brain stimulation methods, I will investigate the neural mechanisms involved in holding pain in working memory, and the extent to which they overlap with working memory for non-painful touch. I will compare participants' performance on painful and non-painful stimulus discrimination tasks requiring them to hold one stimulus in memory and compare it with another, whilst transiently disrupting brain regions known to be involved in tactile working memory.My second aim is to use a well-grounded and rapidly advancing paradigm of memory research called reconsolidation interference to assess how we can interfere with associative pain memories that have already been stabilised into long-term memory. According to this theory, reactivation of a memory trace initiates a window of vulnerability to memory interference. Specifically, it may be possible to use a dual-load paradigm in which neural processes recruited by a cognitive/behavioural task interfere with those required to reconsolidate the memory, destabilising the memory trace. This offers a potential mechanism to erase maladaptive pain memories. To test this possibility, I will use transient, experimentally induced pain in healthy volunteers during a cue conditioning procedure. During a reactivation phase, participants will perform a working memory task that targets either sensory or emotional processing, since those two processes are fundamental to pain experiences. In the final phase, I will measure arousal responses to the visual cues previously paired with pain to determine whether the interference procedure was effective. These studies will determine whether sensory or emotional processing is more important for consolidating pain memories, and therefore more successful at interfering with their reconsolidation. Additionally, in the long term, I would like to apply the successful interventions to spontaneous clinical pain. This will provide insight into the nature of memory for pain in clinical pain samples and direct potential intervention strategies in these populations.The research I am proposing will contribute to our theoretical understanding of memory for pain. Importantly, it will show how working memory for pain differs from or overlaps with tactile working memory, and whether sensory or emotional representations of pain are more predominant in pain memories. In particular, it could shed light on the contributions of somatosensory pathways and affective brain networks to pain memories in conditions of persistent, non-resolving pain. Understanding these processes can provide insight into the nature of pain memory traces and why they may show resistance to erasure. Alongside significant theoretical contributions, my research would have important implications for pain-management strategies and non-pharmacological clinical interventions.