Zeng Pengyu, Wang Tiantian, Zhang Lisan, Guo Fang
Department of Neurobiology, Department of Neurology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
Front Neurol. 2023 Sep 28;14:1160112. doi: 10.3389/fneur.2023.1160112. eCollection 2023.
Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clinical progress on the possible mechanism underlying RLS augmentation. Dysfunction of the dopamine system highly possibly plays a role in the development of RLS augmentation, as dopamine agonists improve desensitization of dopamine receptors, disturb receptor interactions within or outside the dopamine receptor family, and interfere with the natural regulation of dopamine synthesis and release in the neural system. Iron deficiency is also indicated to contribute to RLS augmentation, as low iron levels can affect the function of the dopamine system. Furthermore, genetic risk factors, such as variations in the and genes, have been linked to an increased risk of RLS initiation and augmentation. Additionally, circadian rhythm, which controls the sleep-wake cycle, may also contribute to the worsening of RLS symptoms and the development of augmentation. Recently, Vitamin D deficiency has been suggested to be involved in RLS augmentation. Based on these findings, we propose that the progressive reduction of selective receptors, influenced by various pathological factors, reverses the overcompensation of the dopamine intensity promoted by short-term, low-dose dopaminergic therapy in the development of augmentation. More research is needed to uncover a deeper understanding of the mechanisms underlying the RLS symptom and to develop effective RLS augmentation treatments.
不安腿综合征（RLS）患者的长期药物治疗常常会导致症状恶化，即随着药物剂量增加症状反而加重。症状恶化的原因，尤其是多巴胺治疗引发的症状恶化原因，仍不明确。在此，我们回顾了关于RLS症状恶化潜在机制的最新研究和临床进展。多巴胺系统功能障碍很可能在RLS症状恶化的发展过程中起作用，因为多巴胺激动剂会改善多巴胺受体的脱敏作用，干扰多巴胺受体家族内部或外部的受体相互作用，并干扰神经系统中多巴胺合成和释放的自然调节。铁缺乏也被认为与RLS症状恶化有关，因为低铁水平会影响多巴胺系统的功能。此外，遗传风险因素，如某些基因的变异，与RLS发病和症状恶化风险增加有关。另外，控制睡眠-觉醒周期的昼夜节律也可能导致RLS症状恶化及症状恶化的发展。最近，维生素D缺乏也被认为与RLS症状恶化有关。基于这些发现，我们提出，在症状恶化的发展过程中，受各种病理因素影响，选择性受体的逐渐减少会逆转短期、低剂量多巴胺能治疗所促进的多巴胺强度的过度补偿。需要更多的研究来更深入地了解RLS症状的潜在机制，并开发有效的RLS症状恶化治疗方法。
