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Yanping Tong,1,2 Jie Liu,3 Tao Yang,1,2 Jingwen Wang,4 Tianyou Zhao,4 Yuezhi Kang,1,2 Yongping Fan1,2 1Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Respiratory Medicine, Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, 100026, People’s Republic of China; 4Department of Neurology, Beijing Miyun District Hospital of Traditional Chinese Medicine, Beijing, 101599, People’s Republic of ChinaCorrespondence: Yongping Fan, Email yongpingf@hotmail.comObjective: To investigate the association of pain with plasma C5a levels and other related inflammatory cytokines in neuromyelitis optica spectrum disorders (NMOSD) patients during remission.Participants and Methods: NMOSD patients (n = 87) and healthy controls (HC; n = 44) were consecutively recruited between January 2017 and April 2018. Plasma complement 5 (C5), C5a, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β levels were detected. Visual Analogue Scale (VAS), ID pain scale, 24-item Hamilton Depression Scale (HAMD), Multiple Sclerosis Impact Scale (MSIS-29), and Kurtzke Expanded Disability Status Scale (EDSS) were used to evaluate the degree and types of pain, the existence of depression and anxiety, and the life quality and disability status of patients. Binary logistic regression equation was used to assess the association of pain with plasma C5a levels.Results: Among the 87 NMOSD patients, 40 complained of pain that in 67.5% (27/40) of cases had a neuropathic component (ID pain ≥ 2). Plasma C5a, IL-6, TNF-α, and IL-1β levels were significantly elevated in NMOSD patients than in HC. Plasma C5 levels were negatively correlated with the time from sampling to the last relapse or disease onset.