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Neuromyelitis optica spectrum disorder patients have elevated plasma C5a and inflammatory cytokine levels during remission periods.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease that affects the central nervous system (CNS), resulting in inflammation of specific brain regions, optic nerve, and spinal cord. NMSOD patients have increased complement component C5a and associated inflammatory cytokines in blood during remission. The study findings are published in the journal Neuropsychiatric Disease and Treatment.

Pain is Common in NMOSD

During the remission period, 46% of NMOSD patients reported experiencing pain. Furthermore, the study results revealed that the patients reported other complaints as well, such as increased anxiety, disability, and worse quality of life.

Pain Is Associated with C5a Levels in the Plasma

NMOSD patients with pain had significantly higher levels of plasma C5a compared with healthy controls. This was associated with increased inflammatory cytokines, including IL-1ß and IL-6, in NMOSD patients during remission. Gender and Expanded Disability Status Scale (EDSS) are considered independent factors associated with pain and elevated C5a in NMOSD.

C5a and Pain: Pathophysiological Mechanisms

The interaction between C5a and the C5a cell membrane receptor (C5aR) is related to pathophysiological mechanisms of acute and chronic pain. The types of pain that NMOSD patients can experience include neuropathic pain and painful tonic muscle spasms, as well as pain related to excess loading. C5a/C5aR promotes the recruitment and activation of leukocytes and mediates the synthesis of proinflammatory cytokines, which contribute to inflammatory and neuropathic pain.

AQP4-IgG Antibodies in NMOSD

Elevated AQP4-IgG antibodies are frequently associated with NMOSD. These antibodies trigger the complement pathway, causing inflammation and synthesis of the membrane attack complex (MAC). Eculizumab, which inhibits cleavage of C5 into C5a and C5b, is implicated in reducing relapse risk among AQP4-IgG-positive NMSOD patients.

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C5a is considered to have a role in the development of pain in patients with NMOSD during the period of remission.


Tong, Y., Liu, J., Yang, T., Wang, J., Zhao, T., Kang, Y., & Fan, Y. (2022). Association of Pain with Plasma C5a in Patients with Neuromyelitis Optica Spectrum Disorders During Remission. Neuropsychiatr Dis Treat, 18, 1039-1046. https://doi.org/10.2147/ndt.S359620