Institute of Medical Psychology and Behavioral Immunobiology, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Institute for Medical Education, Centre for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Neuroimmunomodulation. 2023;30(1):250-267. doi: 10.1159/000534467. Epub 2023 Oct 5.
The immune system and the central nervous system exchange information continuously. This communication is a prerequisite for adaptive responses to physiological and psychological stressors. While the implicate relationship between inflammation and pain is increasingly recognized in clinical cohorts, the underlying mechanisms and the possibilities for pharmacological and psychological approaches aimed at neuro-immune communication in pain are not fully understood yet. This calls for preclinical models which build a bridge from clinical research to laboratory research. Experimental models of systemic inflammation (experimental endotoxemia) in humans have been increasingly recognized as an approach to study the direct and causal effects of inflammation on pain perception. This narrative review provides an overview of what experimental endotoxemia studies on pain have been able to clarify so far. We report that experimental endotoxemia results in a reproducible increase in pain sensitivity, particularly for pressure and visceral pain (deep pain), which is reflected in responses of brain areas involved in pain processing. Increased levels of blood inflammatory cytokines are required for this effect, but cytokine levels do not always predict pain intensity. We address sex-dependent differences in immunological responses to endotoxin and discuss why these differences do not necessarily translate to differences in behavioral measures. We summarize psychological and cognitive factors that may moderate pain sensitization driven by immune activation. Together, studying the immune-driven changes in pain during endotoxemia offers a deeper mechanistic understanding of the role of inflammation in chronic pain. Experimental endotoxemia models can specifically help to tease out inflammatory mechanisms underlying individual differences, vulnerabilities, and comorbid psychological problems in pain syndromes. The model offers the opportunity to test the efficacy of interventions, increasing their translational applicability for personalized medical approaches.
免疫系统和中枢神经系统持续地交换信息。这种通讯是对生理和心理应激源产生适应性反应的前提。虽然在临床队列中越来越认识到炎症和疼痛之间的隐含关系，但对于旨在针对疼痛的神经-免疫通讯的潜在机制和药理学及心理学方法的可能性还不完全了解。这就需要建立从临床研究到实验室研究的桥梁的临床前模型。人类的全身性炎症实验模型（实验性内毒素血症）已越来越被认为是研究炎症对疼痛感知的直接和因果影响的一种方法。本综述概述了迄今为止，关于疼痛的实验性内毒素血症研究能够阐明的内容。我们报告说，实验性内毒素血症会导致疼痛敏感性的可重现增加，特别是对压力和内脏疼痛（深部疼痛），这反映在参与疼痛处理的大脑区域的反应中。这种效应需要血液中炎症细胞因子水平升高，但细胞因子水平并不总是预测疼痛强度。我们讨论了免疫对内毒素的反应中的性别依赖性差异，并讨论了为什么这些差异不一定转化为行为测量的差异。我们总结了可能调节免疫激活引起的疼痛敏化的心理和认知因素。总之，研究内毒素血症期间疼痛的免疫驱动变化为炎症在慢性疼痛中的作用提供了更深入的机制理解。实验性内毒素血症模型特别有助于梳理疼痛综合征中个体差异、脆弱性和合并心理问题的炎症机制。该模型提供了测试干预措施疗效的机会，增加了它们对个性化医疗方法的转化适用性。
