Woman Holds Hand

There used to be a time in medicine when patients were generally expected to project a cheerful disposition during ward rounds. This is coupled with a belief in the literal interpretation of the biblical adage “a joyful heart is good medicine” and that being generally optimistic about one’s health can play a role in faster recovery. 

Although it is certainly desirable when patients are optimistic about their futures and are able to maintain a steely commitment to joy during the treatment process, studies have demonstrated that many patients suffer from underlying mental health issues, such as depression and anxiety. 

This is especially made worse in painful, chronic illnesses, such as neuromyelitis optica spectrum disorder (NMOSD). NMOSD is an inflammatory disease that targets the central nervous system, causing severe inflammation-mediated demyelination. The spinal cord and the optic nerve are particularly affected. 

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“Acute bilateral or consecutive optic neuritis leading to severe loss of vision or transverse myelitis resulting in limb weakness, hypoesthesia or bladder dysfunction are the main characteristics of NMOSD, typically with recurrence,” Zhang and colleagues wrote in the Chinese Medical Sciences Journal. 

Varying Types of Pain 

In some rare diseases, various organs are affected insidiously and do not tend to cause acute experiences of pain. However, studies have demonstrated that pain is a major issue in patients with NMOSD. For example, research has found that 80% of participants reported struggling with pain. In comparison with multiple sclerosis, the pain experienced in NMOSD has been reported to be considerably higher. 

Read more about NMOSD etiology 

Two kinds of pain are typically observed in patients with NMOSD. The first is neuropathic pain, which in this disease typically manifests in the thoracolumbar, back, or leg areas. Neuropathic pain in NMOSD is also recognizable in that it is often followed by abnormal thermal sensation. 

The second type of pain experienced by patients with NMOSD is muscle spasms. Patients with NMOSD can sometimes experience muscle spasms in the unilateral or bilateral limbs. This disorder can be treated by drugs such as antiepileptic agents and muscle relaxants. 

“Pain severely influences quality of life in NMOSD patients,” Zhang and colleagues wrote. “Pain imposed the greatest negative physical impacts on overall quality of life, whereas the impact of pain on emotional well-being was controversial.” 

Moderate to Severe Pain

In Neuroimmunology & Neuroinflammation, Ayzenberg and colleagues delved deeper into the issue of chronic pain experienced by patients with NMOSD. They sought to identify the clinical features, risk factors, and impact of pain and depression in patients with AQP4-IgG-seropositive NMOSD. 

As early as the 18th century, girdle-like dysesthesia, spinal pain, and painful spasms have been reported as features of NMOSD. Studies have demonstrated that pain from the disease is the most important predictive factor for quality of life. 

However, even today, the body of literature exploring pain in NMOSD patients remains surprisingly limited. Ayzenberg and colleagues hence decided to conduct a cross-sectional study between 2017 and 2019. They recruited patients with a diagnosis of AQP4-IgG-seropositive NMOSD (N=166). Data was then obtained from the selected patients’ medical records. 

The participants were asked to fill in questionnaires relating to pain severity, how their pain has affected their daily living, and the different sensations of pain. The authors of the study also requested that participants fill in a questionnaire regarding their experiences with mental health and depression. 

Read more about NMOSD treatment 

This study confirms much of what we have known about chronic pain in patients with NMOSD. For example, 75.3% of patients suffered from chronic pain, with just over half of the patients rating the pain as being moderate to severe. In addition about a third of patients reported experiencing neuropathic pain, with the site of the most intense pain being in the trunk or legs. 

The researchers also discovered that the number of previous attacks was significantly associated with the recurrence of pain. In addition, the team found that the number of lesions in the upper 6 thoracic segments only was associated with a higher risk of spasticity-associated pain. 

Another significant finding in this study is that symptomatic pain treatment in patients with NMOSD is largely inadequate. The types of drugs that patients can be prescribed for pain relief are diverse: antidepressants, nonopioid analgesics, and antiepileptic medication (for neuropathic pain). Studies among 40 patients with neuropathic pain who took symptomatic pain relief revealed that only 4 patients self-reported as being pain-free, while others mostly reported moderate to severe pain despite being on treatment. 

There should be two takeaways from this article: the first is that chronic pain is a characteristic feature of patients with NMOSD; hence, it is wise for physicians to assume that patients are in some sort of pain during consultations and ask pertinent questions to gauge the severity of the pain experienced. Second, current pain management regimens are largely inadequate. Our goal as physicians is to get the pain level down to zero. Until then, more research needs to be conducted to investigate how we can achieve this very important objective. 


Zhang X, Xu Y, Pei LJ. Review of neuromyelitis optica spectrum disorder with pain-depression comorbidityChin Med Sci J. 2021;36(4):316-322. doi:10.24920/003859

Ayzenberg I, Richter D, Henke E, et al. Pain, depression, and quality of life in neuromyelitis optica spectrum disorder: a cross-sectional study of 166 AQP4 antibody-seropositive patientsNeurol Neuroimmunol Neuroinflamm. 2021;8(3):e985. doi:10.1212/NXI.0000000000000985