Age, Sex and Spinal Lesions May Be Risk Factors for Neuropathic Pain

New study IDs factors that may predict pain in NMOSD patients

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Age, sex, and spinal lesions may be risk factors for developing pain due to nerve damage — called neuropathic pain — in people with neuromyelitis optica spectrum disorder (NMOSD), according to a new study.

Specifically, an older age at disease onset, female sex, and a greater number of lesions on the thoracic spinal cord may predict neuropathic pain in NMOSD patients, the study found.

The study, “The risk factors of neuropathic pain in neuromyelitis optica spectrum disorder:a retrospective case-cohort study,” was published in the journal BMC Neurology.

Pain is a common symptom of NMOSD, with neuropathic pain being particularly prevalent among patients with the autoimmune disease. Painkillers show little efficacy in resolving such pain, and their use can sometimes be accompanied by side effects like cognitive impairment or fatigue.

Studies have previously identified clinical factors, like age and spinal cord inflammation, as being linked to the occurrence of neuropathic pain in NMOSD patients. However, according to researchers, a full perspective is needed on the risk factors for this type of pain.

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Investigating pain in NMOSD

To address the knowledge gap, a team of scientists in China examined the clinical characteristics associated with neuropathic pain among a group of 86 NMOSD patients. All of the patients were seen at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021.

Neuropathic pain was defined in the study as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” A lesion refers to an area of tissue damage, while the somatosensory system is the network of nerves responsible for producing sensations like touch, temperature, and pain.

Across the entire group of patients, 75 were women, and the mean age at NMOSD onset was 46.2 years. Overall, 37 patients had neuropathic pain and 49 did not — corresponding to a 43% prevalence of neuropathic pain.

To treat their pain, 86.5% of the 37 patients used anti-epileptic drugs, which are commonly used to treat seizures, and 24.3% used antidepressants. Another 13.5% did not use painkillers.

Several clinical features differed between patients who had neuropathic pain and those who didn’t. Specifically, those with neuropathic pain had an older age at onset of NMOSD than those without it.

The spinal cord appeared to be more severely affected by inflammatory attacks among those in the neuropathic pain group. Specifically, more of the members of this group experienced myelitis — spinal cord inflammation — during the first disease episode. The amount of affected spinal cord also was longer in this group, and more of these patients had lesions in the thoracic section of the spine.

Also, a greater proportion of those without neuropathic pain experienced optic neuritis — inflammation to the nerve, called the optic nerve, that sends and receives signals to the eye — during the first disease episode. These patients more often had optic nerve lesions as well, the researchers found.

More people with neuropathic pain used into-the-vein (intravenous) immunoglobulins during a disease attack compared with the no-pain group. Those in the pain group also used more mycophenolate mofetil during periods of remission relative to patients without pain.

The presence of antibodies against aquaporin-4 immunoglobulin G (APQ4-IgG) — the most common NMOSD-causing antibodies — was not significantly linked to neuropathic pain in the study, as has been previously observed.

A final statistical analysis showed that having at least four lesions on the thoracic spine region was a significant risk factor for neuropathic pain, raising the risk by nearly 20 times.

That finding is in line with some previous studies linking spinal lesions with pain, whereas other failed to find a relationship. “Since the association between neuropathic pain and the features of spinal lesions is still controversial,” the researchers noted that more studies will be needed.

Age also was a risk factor — for every five-year increase in age, the risk was increased 1.35 times. Female sex raised the risk of neuropathic pain by about 12 times, a finding that was just shy of being statistically significant.

Sex differences in inflammation, hormones, or genetic predispositions could underlie that finding, but more investigation will be needed, the team said.

“Extended thoracic lesions … age and gender might be independent risk factors of neuropathic pain among patients with NMOSD,” the researchers wrote.

“However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts,” they concluded.