Does multimodal pain treatment affect neurotransmitter turnover and functional connectivity in the brain of patients with chronic pain?

本研究的主要目的是研究跨学科、多模式疼痛治疗对与非特异性慢性背痛相关的人类大脑疼痛处理区域的功能性脑连通性和谷氨酸和GABA神经递质水平改变的短期影响。患者通过耶拿大学医院疼痛治疗科的筛选项目招募，并在治疗前后使用MEGA-PRESS质子磁共振光谱和静息状态功能磁共振成像进行检查。该患者组将与第二组患者进行比较，第二组患者在开始自己的治疗前4周进行相同的磁共振检查，包括重复检查。另外，一个健康的对照组将接受一次相同的核磁共振方案。基于这些数据，我们提出了以下问题：慢性疼痛患者大脑中的神经化学和功能改变是如何表现出来的？它们之间是如何联系的，多模式治疗在多大程度上影响了这些改变？因此，大脑疼痛处理的中枢敏感化假说将得到验证。这一假说认为，抑制性神经递质功能的减少是导致永久性神经元兴奋失控的根本原因。在多模式治疗后，后者的潜在调节也将被评估。进一步的分析将提取的MR参数与表征躯体和心理损伤严重程度的临床评分相关联，以调查治疗结果是否有所改善，以及这是否也反映在代谢和功能改变上。除了为慢性疼痛的大脑表现提供新的和更深入的见解外，对这些假设的验证将进一步为客观和区分分析大脑中疼痛处理的治疗相关规范化开辟新的机会。

The major aim of this proposal is to investigate short term effects of an interdisciplinary, multimodal pain therapy treatment on alterations of functional brain connectivity and neurotransmitter levels of gluta¬mate and GABA in pain processing regions of the human brain that are related to nonspecific chronic back pain. Patients are recruited via a screening program of the Pain Therapy Section at the University Hospital Jena and are examined before and after treatment with MEGA-PRESS proton MR spectroscopy and resting state functional MR imaging. This patient group will be compared to a second patient group that undergoes the same MR examination including its repetition after four weeks before they start their own therapy. In addition, a healthy control group will undergo the same MR protocol once. Based on these data the following questions are addressed: How do neurochemical and functional alterations manifest themselves in the brain of chronic pain patients? How are they connected among each other and inasmuch does multimodal treatment affect these alterations? Thereby, the hypothesis of central sensitization of cerebral pain processing will be tested. This hypothesis assumes reduced inhibitory neurotransmitter functions as the underlying cause leading to deregulated permanent neuronal excitation. Potential regulation of the latter following multimodal therapy will be also assessed. Further analyses will correlate the extracted MR parameters with clinical scores that characterize the severity of somatic and psychological impairments to investigate whether treatment outcome has improved and whether this is also reflected in metabolic and functional alterations. Besides providing new and deeper insight into the cerebral manifestations of chronic pain, verification of the hypotheses will further open new opportunities for an objective and differentiated analysis of therapy related regularization of pain processing in the brain.