Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Pain in neuromyelitis optica—prevalence, pathogenesis and therapy

Abstract

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 1

    Wingerchuk, D. M., Lennon, V. A., Lucchinetti, C. F., Pittock, S. J. & Weinshenker, B. G. The spectrum of neuromyelitis optica. Lancet Neurol. 6, 805–815 (2007).

    CAS  PubMed  Google Scholar 

  2. 2

    Papadopoulos, M. C. & Verkman, A. S. Aquaporin water channels in the nervous system. Nat. Rev. Neurosci. 14, 265–277 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Lennon, V. A. et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364, 2106–2112 (2004).

    CAS  Google Scholar 

  4. 4

    Jarius, S. & Wildemann, B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol. 23, 661–683 (2013).

    CAS  PubMed  Google Scholar 

  5. 5

    Bradl, M. et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann. Neurol. 66, 630–643 (2009).

    CAS  PubMed  Google Scholar 

  6. 6

    Bennett, J. L. et al. Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann. Neurol. 66, 617–629 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Kinoshita, M. et al. Neuromyelitis optica: passive transfer to rats by human immunoglobulin. Biochem. Biophys. Res. Commun. 386, 623–627 (2009).

    CAS  PubMed  Google Scholar 

  8. 8

    Saadoun, S. et al. Intra-cerebral injection of neuromyelitis optica imunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 133, 349–361 (2010).

    PubMed  PubMed Central  Google Scholar 

  9. 9

    Bradl, M. & Lassmann, H. Experimental models of neuromyelitis optica. Brain Pathol. 24, 74–82 (2014).

    CAS  PubMed  Google Scholar 

  10. 10

    Sato, D. K., Lana-Peixoto, M. A., Fujihara, K. & de Seze, J. Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol. 23, 647–660 (2013).

    PubMed  Google Scholar 

  11. 11

    Kanamori, Y. et al. Pain in neuromyelitis optica and its effect on quality of life: a cross-sectional study. Neurology 77, 652–658 (2011).

    CAS  PubMed  Google Scholar 

  12. 12

    Qian, P. et al. Association of neuromyelitis optica with severe and intractable pain. Arch. Neurol. 69, 1482–1487 (2012).

    PubMed  PubMed Central  Google Scholar 

  13. 13

    Zhao, S., Mutch, K., Elsone, L., Nurmikko, T. & Jacob, A. Neuropathic pain in neuromyelitis optica affects activities of daily living and quality of life. Mult. Scler. http://dx.doi.org/10.1177/1352458514522103.

  14. 14

    Pellkofer, H. L. et al. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica. PLoS ONE 8, e71500 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Kim, S. M., Go, M. J., Sung, J. J., Park, K. S. & Lee, K. W. Painful tonic spasm in neuromyelitis optica: incidence, diagnostic utility, and clinical characteristics. Arch. Neurol. 69, 1026–1031 (2012).

    PubMed  Google Scholar 

  16. 16

    Evangelopoulos, M. E. et al. Neuromyelitis optica spectrum disease with positive autoimmune indices: a case report and review of the literature. Case Rep. Med. 2011, 393568 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Elsone, L. et al. Neuropathic pruritus (itch) in neuromyelitis optica. Mult. Scler. 19, 475–479 (2013).

    PubMed  Google Scholar 

  18. 18

    Milligan, E. D. & Watkins, L. R. Pathological and protective roles of glia in chronic pain. Nat. Rev. Neurosci. 10, 23–36 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Marchand, F., Perretti, M. & McMahon, S. B. Role of the immune system in chronic pain. Nat. Rev. Neurosci. 6, 521–532 (2005).

    CAS  PubMed  Google Scholar 

  20. 20

    Xanthos, D. N. & Sandkühler, J. Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity. Nat. Rev. Neurosci. 15, 43–53 (2014).

    CAS  PubMed  Google Scholar 

  21. 21

    Basbaum, A. I., Bautista, D. M., Scherrer, G. & Julius, D. Cellular and molecular mechanisms of pain. Cell 139, 267–284 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Lu, Y. & Perl, E. R. Selective action of noradrenaline and serotonin on neurones of the spinal superficial dorsal horn in the rat. J. Physiol. 582, 127–136 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Sandkühler, J. Models and mechanisms of hyperalgesia and allodynia. Physiol. Rev. 89, 707–758 (2009).

    PubMed  Google Scholar 

  24. 24

    Lucchinetti, C. F. et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 125, 1450–1461 (2002).

    PubMed  PubMed Central  Google Scholar 

  25. 25

    Misu, T. et al. Presence of six different lesion types suggests diverse mechanisms of tissue injury in the lesions of neuromyelitis optica. Acta Neuropathol. 125, 815–827 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Lucchinetti, C. F. et al. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol. 24, 83–97 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Jarius, S. et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J. Neuroinflammation 9, 14 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Wingerchuk, D. M., Hogancamp, W. F., O'Brien, P. C. & Weinshenker, B. G. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 53, 1107–1114 (1999).

    CAS  PubMed  Google Scholar 

  29. 29

    Collongues, N. et al. Neuromyelitis optica in France: a multicenter study of 125 patients. Neurology 74, 736–742 (2010).

    CAS  PubMed  Google Scholar 

  30. 30

    Wingerchuk, D. M., Lennon, V. A., Pittock, S. J., Lucchinetti, C. F. & Weinshenker, B. G. Revised diagnostic criteria for neuromyelitis optica. Neurology 66, 1485–1489 (2006).

    CAS  Google Scholar 

  31. 31

    Nakamura, M. et al. Preferential spinal central gray matter involvement in neuromyelitis optica. An MRI study. J. Neurol. 255, 163–170 (2008).

    CAS  PubMed  Google Scholar 

  32. 32

    Roemer, S. F. et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 130, 1194–1205 (2007).

    PubMed  Google Scholar 

  33. 33

    Misu, T., Fujihara, K., Nakashima, I., Sato, S. & Itoyama, Y. Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica. Neurology 65, 1479–1482 (2005).

    CAS  PubMed  Google Scholar 

  34. 34

    Hinson, S. R. et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 69, 2221–2231 (2007).

    CAS  Google Scholar 

  35. 35

    Rossi, A., Ratelade, J., Papadopoulos, M. C., Bennett, J. L. & Verkman, A. S. Neuromyelitis optica IgG does not alter aquaporin-4 water permeability, plasma membrane M1/M23 isoform content, or supramolecular assembly. Glia 60, 2027–2039 (2012).

    PubMed  PubMed Central  Google Scholar 

  36. 36

    Hinson, S. R. et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J. Exp. Med. 205, 2473–2481 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Marignier, R. et al. Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain 133, 2578–2591 (2010).

    PubMed  Google Scholar 

  38. 38

    Matsuoka, T., Suzuki, S. O., Suenaga, T., Iwaki, T. & Kira, J. Reappraisal of aquaporin-4 astrocytopathy in Asian neuromyelitis optica and multiple sclerosis patients. Brain Pathol. 21, 516–532 (2011).

    CAS  PubMed  Google Scholar 

  39. 39

    Matsushita, T. et al. Astrocytopathy in neuromyelitis optica, multiple sclerosis and Balo's disease [Japanese]. Rinsho Shinkeigaku 51, 898–900 (2011).

    PubMed  Google Scholar 

  40. 40

    Sharma, R. et al. Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination. Acta Neuropathol. 120, 223–236 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Parratt, J. D. & Prineas, J. W. Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes. Mult. Scler. 16, 1156–1172 (2010).

    PubMed  Google Scholar 

  42. 42

    Nishiyama, S. et al. A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset. Neurology 72, 1960–1961 (2009).

    CAS  PubMed  Google Scholar 

  43. 43

    Uzawa, A., Masahiro, M. & Kuwabara, S. Cytokines and chemokines in neuromyelitis optica: pathogenetic and therapeutic implications. Brain Pathol. 24, 67–73 (2014).

    CAS  PubMed  Google Scholar 

  44. 44

    Olechowski, C. J., Truong, J. J. & Kerr, B. J. Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE). Pain 141, 156–164 (2009).

    CAS  PubMed  Google Scholar 

  45. 45

    Gruber-Schoffnegger, D. et al. Induction of thermal hyperalgesia and synaptic long-term potentiation in the spinal cord lamina I by TNF-α and IL-1β is mediated by glial cells. J. Neurosci. 33, 6540–6551 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Park, C. K. et al. Resolving TRPV1- and TNF-α-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1. J. Neurosci. 31, 15072–15085 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Ikeda, H. et al. Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science 312, 1659–1662 (2006).

    CAS  PubMed  Google Scholar 

  48. 48

    Drdla, R., Gassner, M., Gingl, E. & Sandkühler, J. Induction of synaptic long-term potentiation after opioid withdrawal. Science 325, 207–210 (2009).

    CAS  PubMed  Google Scholar 

  49. 49

    Meng, X. et al. Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model. Pain 154, 294–305 (2013).

    CAS  PubMed  Google Scholar 

  50. 50

    Nakatsuka, T., Tsuzuki, K., Ling, J. X., Sonobe, H. & Gu, J. G. Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord. J. Neurophysiol. 89, 3243–3252 (2003).

    CAS  PubMed  Google Scholar 

  51. 51

    Hansen, R. R. & Malcangio, M. Astrocytes—multitaskers in chronic pain. Eur. J. Pharmacol. 716, 120–128 (2013).

    CAS  PubMed  Google Scholar 

  52. 52

    Donnelly-Roberts, D., McGaraughty, S., Shieh, C. C., Honore, P. & Jarvis, M. F. Painful purinergic receptors. J. Pharmacol. Exp. Ther. 324, 409–415 (2008).

    CAS  PubMed  Google Scholar 

  53. 53

    Jarius, S. & Wildemann, B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat. Rev. Neurol. 6, 383–392 (2010).

    CAS  PubMed  Google Scholar 

  54. 54

    Moga, D., Hof, P. R., Vissavajjhala, P., Moran, T. M. & Morrison, J. H. Parvalbumin-containing interneurons in rat hippocampus have an AMPA receptor profile suggestive of vulnerability to excitotoxicity. J. Chem. Neuroanat. 23, 249–253 (2002).

    CAS  PubMed  Google Scholar 

  55. 55

    Zeilhofer, H. U., Wildner, H. & Yevenes, G. E. Fast synaptic inhibition in spinal sensory processing and pain control. Physiol. Rev. 92, 193–235 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Coull, J. A. et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438, 1017–1021 (2005).

    CAS  PubMed  Google Scholar 

  57. 57

    Susser, E., Sprecher, E. & Yarnitsky, D. Paradoxical heat sensation in healthy subjects: peripherally conducted by Aδ or C fibres? Brain 122, 239–246 (1999).

    PubMed  Google Scholar 

  58. 58

    Sigel, E. et al. The major central endocannabinoid directly acts at GABAA receptors. Proc. Natl Acad. Sci. USA 108, 18150–18155 (2011).

    CAS  PubMed  Google Scholar 

  59. 59

    Kallendrusch, S. et al. Intrinsic up-regulation of 2-AG favors an area specific neuronal survival in different in vitro models of neuronal damage. PLoS ONE 7, e51208 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Martinez-Hernandez, A., Bell, K. P. & Norenberg, M. D. Glutamine synthetase: glial localization in brain. Science 195, 1356–1358 (1977).

    CAS  PubMed  Google Scholar 

  61. 61

    Albrecht, J., Sidoryk-Wegrzynowicz, M., Zielinska, M. & Aschner, M. Roles of glutamine in neurotransmission. Neuron Glia Biol. 6, 263–276 (2010).

    PubMed  Google Scholar 

  62. 62

    Behbehani, M. M. Functional characteristics of the midbrain periaqueductal gray. Prog. Neurobiol. 46, 575–605 (1995).

    CAS  PubMed  Google Scholar 

  63. 63

    Kremer, L. et al. Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult. Scler. http://dx.doi.org/10.1177/1352458513507822.

  64. 64

    Verkman, A. S., Phuan P.-W., Asavapanumas, N. & Tradtrantip, L. Biology of AQP4 and anti-AQP4 antibody: therapeutic implications for NMO. Brain Pathol. 23, 684–695 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Kumar, A. & Loane, D. J. Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav. Immun. 26, 1191–1201 (2012).

    PubMed  Google Scholar 

  66. 66

    Wang, X. et al. Morphine activates neuroinflammation in a manner parallel to endotoxin. Proc. Natl Acad. Sci. USA 109, 6325–6330 (2012).

    CAS  PubMed  Google Scholar 

  67. 67

    Wallace, M. S., Lam, V. & Schettler, J. NGX426, an oral AMPA-kainate antagonist, is effective in human capsaicin-induced pain and hyperalgesia. Pain Med. 13, 1601–1610 (2012).

    PubMed  Google Scholar 

  68. 68

    Volpi, C., Fazio, F. & Fallarino, F. Targeting metabotropic glutamate receptors in neuroimmune communication. Neuropharmacology 63, 501–506 (2012).

    CAS  PubMed  Google Scholar 

  69. 69

    Sandkühler, J. & Lee, J. How to erase memory traces of pain and fear. Trends Neurosci. 36, 343–352 (2013).

    PubMed  PubMed Central  Google Scholar 

  70. 70

    Drdla-Schutting, R., Benrath, J., Wunderbaldinger, G. & Sandkühler, J. Erasure of a spinal memory trace of pain by a brief, high-dose opioid administration. Science 335, 235–238 (2012).

    CAS  PubMed  Google Scholar 

  71. 71

    Taira, T. et al. A new approach to control central deafferentation pain: spinal intrathecal baclofen. Stereotact. Funct. Neurosurg. 65, 101–105 (1995).

    CAS  PubMed  Google Scholar 

  72. 72

    Dykstra, D., Stuckey, M., DesLauriers, L., Chappuis, D. & Krach, L. Intrathecal baclofen in the treatment of spasticity. Acta Neurochir. Suppl. 97, 163–171 (2007).

    CAS  PubMed  Google Scholar 

  73. 73

    Rog, D. J., Nurmikko, T. J., Friede, T. & Young, C. A. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 27, 812–819 (2005).

    Google Scholar 

  74. 74

    Hunt, S. P. & Mantyh, P. W. The molecular dynamics of pain control. Nat. Rev. Neurosci. 2, 83–91 (2001).

    CAS  PubMed  Google Scholar 

  75. 75

    Pittock, S. J. et al. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch. Neurol. 63, 964–968 (2006).

    PubMed  Google Scholar 

  76. 76

    Kitic, M. et al. Intrastriatal injection of interleukin 1 β triggers the formation of neuromyelitis optica-like lesions in NMO-IgG seropositive rats. Acta Neuropathol. Commun. 1, 5 (2013).

    PubMed  PubMed Central  Google Scholar 

  77. 77

    Uzawa, A. et al. Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. Mult. Scler. 16, 1443–1452 (2010).

    CAS  PubMed  Google Scholar 

  78. 78

    Uzawa, A. et al. Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis. J. Neurol. 256, 2082–2084 (2009).

    CAS  PubMed  Google Scholar 

  79. 79

    Icoz, S. et al. Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients. Int. J. Neurosci. 120, 71–75 (2010).

    PubMed  Google Scholar 

  80. 80

    Wei, X. H. et al. The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection. Exp. Neurol. 241, 159–168 (2013).

    CAS  PubMed  Google Scholar 

  81. 81

    Guptarak, J. et al. Inhibition of IL-6 signaling: a novel therapeutic approach to treating spinal cord injury pain. Pain 154, 1115–1128 (2013).

    CAS  PubMed  Google Scholar 

  82. 82

    DeLeo, J. A., Colburn, R. W., Nichols, M. & Malhotra, A. Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J. Interferon Cytokine Res. 16, 695–700 (1996).

    CAS  PubMed  Google Scholar 

  83. 83

    Arruda, J. L., Sweitzer, S., Rutkowski, M. D. & DeLeo, J. A. Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Res. 879, 216–225 (2000).

    CAS  PubMed  Google Scholar 

  84. 84

    Araki, M. et al. Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod. Rheumatol. 23, 827–831 (2013).

    CAS  PubMed  Google Scholar 

  85. 85

    Ishizu, T. et al. Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 128, 988–1002 (2005).

    PubMed  Google Scholar 

  86. 86

    Wang, H. et al. Interleukin 17 gene polymorphism is associated with anti-aquaporin 4 antibody-positive neuromyelitis optica in the Southern Han Chinese—a case control study. J. Neurol. Sci. 314, 26–28 (2012).

    CAS  PubMed  Google Scholar 

  87. 87

    Wang, H. H. et al. Interleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse. J. Clin. Neurosci. 18, 1313–1317 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88

    Wang, K. C. et al. Elevated plasma high-mobility group box 1 protein is a potential marker for neuromyelitis optica. Neuroscience 226, 510–516 (2012).

    CAS  PubMed  Google Scholar 

  89. 89

    Ren, P. C. et al. High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes. Brain Res. Bull. 88, 332–337 (2012).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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.

Author information

Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Monika Bradl.

Ethics declarations

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.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bradl, M., Kanamori, Y., Nakashima, I. et al. Pain in neuromyelitis optica—prevalence, pathogenesis and therapy. Nat Rev Neurol 10, 529–536 (2014). https://doi.org/10.1038/nrneurol.2014.129

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing