Social buffering in pain resilience and resolution

众所周知，社会和心理因素可以通过前额皮质、前岛和杏仁核等大脑区域调节疼痛处理。然而，到目前为止，关于社会环境是否以及如何影响临床相关疼痛综合征的解决或持续，以及如果有，哪些是分子机制，几乎没有系统的证据。为了研究这些问题，我们将研究社会因素对两种潜在可逆性疼痛患者的影响，并在动物模型中进行研究。这些平行的方法将使我们能够明确社会因素对疼痛恢复和恢复的临床重要性，以及潜在的分子机制。在临床部分，我们将重点关注A)以疼痛为主要症状的硼替佐米诱导的周围神经病变（BIPN）患者，这是至少30%接受治疗的癌症患者的剂量限制并发症，B)四肢骨折后出现复杂区域疼痛综合征（CRPS）的患者。在这两种情况下，许多患者的疼痛都能迅速缓解，但另一些患者的疼痛可能会严重且持续很长时间。决定疼痛综合征缓解或持续的因素包括外周和中枢神经系统反应的改变、神经炎症以及心理和社会变量的个体差异。本项目旨在了解在现实世界中，社会因素对疼痛缓解和疼痛慢性化的外周和分子标志物的影响。为此，我们将使用生态瞬时评估（EMA）来表征疼痛迅速缓解和慢性疼痛患者的社会环境，并评估他们与周围疼痛标志物的关系。同时，我们将在BIPN动物模型中测试社会和非社会环境下的疼痛反应和缓解。这项动物研究将明确社会因素调节疼痛的分子过程，从而为社会因素和疼痛如何在分子水平上相互作用提供新的见解。

Social and psychological factors are known to modulate pain processing via brain areas such as the prefrontal cortex, the anterior insula and the amygdala. However, so far there is little systematic evidence of whether and how the social environment affects resolution or persistence of clinically relevant pain syndromes and if so, which are the molecular mechanisms. To study these questions, we will investigate the impact of social factors in patients with two potentially reversible pain conditions, and in an animal model. These parallel approaches will allow us to specify the clinical importance of social factors for pain resilience and recovery, and the underlying molecular mechanisms. In the clinical part, we will focus on A) patients with bortezomib induced peripheral neuropathy (BIPN), with pain as the major symptom, which is the dose limiting complication in at least 30% of treated cancer patients, and B) patients with complex regional pain syndrome (CRPS) after a bone fracture of an extremity. In both conditions, resolution is prompt in many patients, but pain can be severe and long lasting in others. Factors determining resolution or persistence of the pain syndrome include alterations in peripheral and central nervous system responses, neuro-inflammation, as well as individual differences in psychological and social variables. This project aims to understand the effect of social factors on peripheral and molecular markers of pain resolution and pain chronification in a real-world context. To do so, we will use ecological momentary assessments (EMA) to characterize the social environment of patients that show prompt pain remission and those that suffer from chronic pain, and assess their relationship with peripheral pain markers. In parallel, we will test pain responses and remission in a social and non-social context in an animal model of BIPN. This animal work will specify the molecular processes through which social factors modulate pain, and thus provide novel insights into how social factors and pain interact on a molecular level.