Association of Pain with Plasma C5a in Patients with Neuromyelitis Optica Spectrum Disorders During Remission

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. NMOSD patients with pain had higher plasma C5a levels, and they suffered from a higher disability, more anxiety, and worse life quality compared to those patients without pain. In NMOSD patients with pain, there were not significant differences between plasma levels of C5, C5a, IL-6, TNF-α, or IL-1β, regardless of neuropathic pain or not. Binary logistic regression showed that the OR of plasma C5a level was 1.002, with gender and EDSS score were identified as independent factors associated with pain in NMOSD.Conclusion: NMOSD patients during remission had elevated C5a and related inflammatory cytokines levels in peripheral blood. Elevated C5a may have a unique role in the pathogenesis of pain in NMOSD patients.Keywords: neuromyelitis optica spectrum disorders, remission, pain, C5a