University of Manchester, Manchester, UK.
University of Cambridge, Cambridge, UK.
Eur J Pain. 2023 Jul;27(6):766-778. doi: 10.1002/ejp.2093. Epub 2023 Mar 30.
Understanding the mechanisms behind the influence of expectation and context on pain perception is crucial for improving analgesic treatments. Prediction error (PE) signals how much a noxious stimulus deviates from expectation and is therefore crucial for our understanding of pain perception. It is thought that the brain engages in 'adaptive coding' of pain PE, such that sensitivity to unexpected outcomes is modulated by contextual information. While there is behavioural evidence that pain is coded adaptively, and evidence that reward PE signals are coded adaptively, controversy remains regarding the underlying neural mechanism of adaptively-coded pain PEs.
A cued-pain task was performed by 19 healthy adults while undergoing FMRI scanning. BOLD responses to the task were tested using an axiomatic approach to identify areas that may code pain PE adaptively.
The left dorsal anterior insula demonstrated a pattern of response consistent with adaptively-coded pain PE. Signals from this area were sensitive to both predicted pain magnitudes on the instigation of expectation, and the unexpectedness of pain delivery. Crucially however, the response at pain delivery was consistent with the local context of the pain stimulation, rather than the absolute magnitude of delivered pain, a pattern suggestive of an adaptively-coded PE signal.
The study advances our understanding of the neural basis of pain prediction. Alongside existing evidence that the periaqueductal grey codes pain PE and the posterior insula codes pain magnitude, the results highlight a distinct contribution of the left dorsal anterior insula in the processing of pain.
Although there is behavioural evidence that pain is coded adaptively, the neural mechanisms serving this process are not well understood. This study used functional MRI to provide the first evidence that the left dorsal anterior insula, an area associated with aversive learning, responds to pain in a manner consistent with the adaptive coding of pain prediction error. This study aids our understanding of the neural basis of subjective pain representation, and thus can contribute to the advancement of analgesic treatments.
理解期望和背景对疼痛感知的影响背后的机制对于改善镇痛治疗至关重要。预测误差 (PE) 信号表明有害刺激与预期的偏差程度，因此对于我们理解疼痛感知至关重要。人们认为大脑会对疼痛 PE 进行“适应性编码”，使得对意外结果的敏感性受到上下文信息的调节。虽然有行为证据表明疼痛是适应性编码的，并且奖励 PE 信号是适应性编码的，但关于适应性编码的疼痛 PE 的潜在神经机制仍存在争议。
19 名健康成年人在进行 fMRI 扫描时执行了提示性疼痛任务。使用公理方法测试任务的 BOLD 反应，以确定可能适应性编码疼痛 PE 的区域。
左背侧前岛叶表现出与适应性编码疼痛 PE 一致的反应模式。该区域的信号对预期开始时预测的疼痛幅度以及疼痛传递的意外性都很敏感。然而，至关重要的是，疼痛传递时的反应与疼痛刺激的局部背景一致，而不是与传递的疼痛的绝对幅度一致，这种模式提示了适应性编码的 PE 信号。
该研究推进了我们对疼痛预测神经基础的理解。除了已有证据表明导水管周围灰质编码疼痛 PE 和后岛叶编码疼痛幅度外，结果还突出了左背侧前岛叶在疼痛处理中的独特贡献。
尽管有行为证据表明疼痛是适应性编码的，但这一过程的神经机制尚不清楚。本研究使用功能性磁共振成像提供了第一个证据，即与厌恶学习相关的左背侧前岛叶以与疼痛预测误差的适应性编码一致的方式对疼痛做出反应。这项研究有助于我们理解主观疼痛表现的神经基础，从而有助于推进镇痛治疗的发展。
