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Pain in neuromyelitis optica—prevalence, pathogenesis and therapy


Terrible, agonizing, wretched, sickening and unbearable—these are words frequently used by patients with neuromyelitis optica (NMO) to describe a very common symptom of their disease: pain. More than 80% of patients with NMO experience pain from this condition, which severely affects their quality of life. At present, there is no known therapy that produces satisfactory relief from NMO-associated pain. In fact, contemporary pain therapy is largely ineffective in these patients, suggesting that the mechanisms underlying pain in NMO differ substantially from those of other treatable causes of pain. Until now, the near-complete neglect of research into pain mechanisms in NMO has precluded rational pain therapy. In this Perspectives article, expertise from the fields of neuroimmunology, neurology and pain research is combined to explore, for the first time, the mechanisms underlying pain in patients with NMO, and to identify molecular and cellular targets for therapy.

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Figure 1: Nociceptive pathways in NMO.
Figure 2: Stages of neuromyelitis optica lesions and key players and events in the development of pain.


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We thank Takashi Yamamura for being the first to call our attention to the connection between neuromyelitis optica and pain. Our work is supported by the Austrian Science Fund (grant numbers P25240-B24 to M.B., I916-B13 [International Programme, Eugène Devic European Network] to H.L. and P22306-B19 to J.S.), and in part by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology and the Ministry of Health, Labor and Welfare of Japan to K.F.

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All authors researched data for the article, and contributed to discussion of content and review/editing of the manuscript before submission. M.B., H.L. and J.S. wrote the article.

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Correspondence to Monika Bradl.

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Competing interests

M.B. has received travel support from Mitsubishi Tanabe. H.L. is a consultant for Amgen, Biogen and Baxter Healthcare and has received speaker honoraria from Novartis, Biogen, Merck Serono and TEVA. I.N. has received travel funding and speaker honoraria from Bayer Yakuhin, Biogen Idec Japan, Mitsubishi Tanabe and Novartis, and research funding from Mitsubishi Chemical Medience. T.M. has received speaker honoraria from Bayer Schering, Biogen Idec Japan, Mitsubishi Tanabe, Asahi Kasei Medical and Astellas, and research support from Bayer Schering, Biogen Idec Japan, Asahi Kasei Kuraray Medical, the Chemo-Sero-Therapeutic Research Institute, TEVA, Mitsubishi Tanabe and Teijin. K.F. is on the scientific advisory boards for Bayer Schering, Biogen Idec, Mitsubishi Tanabe, Novartis, Chugai, Ono, Nihon, Merck Serono and Alexion; he has received travel funding and speaker honoraria from Bayer Schering, Biogen Idec, Eisai, Mitsubishi Tanabe, Novartis, Astellas, Takeda, Asahi Kasei Medical and Daiichi Sankyo; and has received research support from Bayer Schering, Biogen Idec Japan, Asahi Kasei Medical, the Chemo-Sero-Therapeutic Research Institute, TEVA, Mitsubishi Tanabe, Teijin, Eisai and Kowa. J.S. has received speaker honoraria from: Astra Zeneca, CT Arzneimittel, DR. KADE, Eli Lilly, Grünenthal, Janssen-Cilag, Mundipharma, Pfizer, TEVA. He is also a member of the scientific advisory board for Grünenthal. Y.K. declares no competing interests.

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Bradl, M., Kanamori, Y., Nakashima, I. et al. Pain in neuromyelitis optica—prevalence, pathogenesis and therapy. Nat Rev Neurol 10, 529–536 (2014).

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