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Computational Models of Descending Pain Regulatory Networks in Chronic Pain

慢性疼痛中下行疼痛调节网络的计算模型

基本信息

批准号：
2891554
负责人：
金额：
--
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2891554
关键词：
Computational Models Descending Pain Regulatory

项目摘要

With one in four people suffering from chronic pain in their lifetime, chronic pain is a global concern. Developing better computational models of the systems involved, in order to understand the processes of chronification, is vital for continued progress towards treatment. One key feature of acute and chronic pain perception is the modulation of ascending nociceptive pathways by descending regulatory networks. These descending circuits become dysfunctional in patients with chronic pain, with previous neurophysiological evidence suggesting their dysfunction may be due to disrupted cortical control of brainstem nuclei and rostral ventral medulla. There are clear neurophysiological features that mark their correct and dysfunctional behaviour, alongside data collected in rodents from other labs. However, computational models of descending pain networks are currently absent, and thus it is not clear why they become dysfunctional. Therefore, in line with the EPSRC Healthcare Technologies theme, I will use control theory to develop a computational model of these networks. I will then simulate their dysfunction by treating the ascending-descending pathways as a closed-loop control system to understand why they are dysfunctional in chronic pain. The implications of this research could provide targets for the pharmacological treatment of pain, and a computational model would provide predictions about the behaviour of these circuits, which could then become avenues for further experimental and pharmacological research.

四分之一的人一生中患有慢性疼痛，慢性疼痛是一个全球性的问题。开发更好的相关系统计算模型，以了解时间化过程，对于治疗的持续进展至关重要。急性和慢性疼痛感知的一个关键特征是通过下行调节网络调节上行伤害感受通路。这些下行回路在慢性疼痛患者中变得功能障碍，之前的神经生理学证据表明它们的功能障碍可能是由于脑干核和延髓头侧腹侧皮质控制受损所致。除了从其他实验室收集的啮齿动物数据外，还有明显的神经生理学特征标志着它们的正确行为和功能失调行为。然而，目前尚不存在下行疼痛网络的计算模型，因此尚不清楚它们为何会出现功能障碍。因此，根据 EPSRC 医疗保健技术主题，我将使用控制理论来开发这些网络的计算模型。然后，我将通过将上升-下降通路视为闭环控制系统来模拟它们的功能障碍，以了解为什么它们在慢性疼痛中功能障碍。这项研究的意义可以为疼痛的药物治疗提供目标，而计算模型将提供对这些回路行为的预测，从而可以成为进一步实验和药理学研究的途径。