Researchers found elevated plasma levels of complement 5 (C5)-a and other inflammatory cytokines in patients with neuromyelitis optica spectrum disorder (NMOSD) during remission, as published in Neuropsychiatric Disease and Treatment.

This is the first study to demonstrate the relationship between C5a levels in peripheral blood and pain in patients with NMOSD during remission, the authors said.

The study recruited 87 patients with NMOSD and 44 healthy controls, and plasma levels of various inflammatory cytokines including C5, C5a, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were measured.

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The researchers also evaluated the degree and types of pain, psychiatric comorbidities, and disability in the patients using various standardized tools including the Visual Analogue Scale, ID Pain scale, 24-Item Hamilton Depression Scale, Multiple Sclerosis Impact Scale, and Kurtzke Expanded Disability Status Scale. 

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Forty-six percent of patients with NMOSD reported current pain. Notably, plasma levels of C5a, IL-6, TNF-α, and IL-1 were significantly elevated in patients with NMOSD when compared with healthy controls.

Patients with pain had higher levels of C5a, regardless of the type of pain, and suffered from a higher disability, more anxiety, and worse quality of life compared to those patients without pain. C5a levels were negatively correlated to the time interval from sampling to the last relapse or disease onset.

The study results suggest that C5a may play a unique role in the pathogenesis of pain in NMOSD, especially during remission. Further studies may be warranted to further understand the role of C5a in pain modulation in this patient population, which may further facilitate the development of therapeutic modalities for pain control.


Tong Y, Liu J, Yang T, et al. Association of pain with plasma C5a in patients with neuromyelitis optica spectrum disorders during remission. Neuropsychiatr Dis Treat. 2022;18:1039-1046. Published online May 17, 2022. doi:10.2147/NDT.S359620