Researchers Identify Causes of Centralized Pain in Patients with Multiple Sclerosis

According to Darin T. Okuda, MD, Chief of the Neuro-Immunology Division, Barrow Neurological Institute (BNI) of St. Joseph's Hospital and Medical Center in Phoenix, Arizona, approximately 30-40% of patients with multiple sclerosis (MS) suffer from central neuropathic pain (CNP), focused symmetrically in both feet and legs and often accompanied by cold allodynia and deep hyperesthesia. The etiology of such pain is currently unknown.

Okuda gave a poster presentation at the American Academy of Neurology (AAN) 2013 Annual Meeting in the “Multiple Sclerosis: Quality of Life and MA Symptoms” session which described a study to determine a neuro-anatomic cause for the central pain observed in MS patients.

Investigators performed parallel clinical and neuro-anatomical studies. Okuda and his colleagues conducted a clinical investigation of consecutively acquired MS patients, with and without CNP, within a single MS center (BNI). They used a multivariate logistic regression model, incorporating significant covariates, to assess the relationship between an upper central thoracic spinal cord focus and CNP. To identify the hypothesized autonomic interneurons with bilateral descending projections to lumbosacral sensory neurons, anterograde and retrograde labeling experiments with cholera toxin subunit B (CTb) and fluorescent tracers were performed in three animal species (rat, cat, and monkey).

Clinical data were available in MS patients with CNP (n=32; 23 females; median age 34.6 years [range: 27.4-45.5]) and without CNP (n=30; 22 females; median age 36.6 years [range: 31.6-47.1]) CNP. Sagital STIR MRI sequences of the thoracic spine showed that MS patients with CNP are distinguished by the presence of a lesion focused in the center of the mid-thoracic spinal cord. In addition, in these patients neurons with bilateral descending projections to the lumbosacral superficial dorsal horn are concentrated in the autonomic intermediomedial (IMM) nucleus surrounding the mid-thoracic central canal.

The value of a centrally focused lesion between spinal cord levels T1-T6 in relation to CNP demonstrated a sensitivity of 96.9% (95% CI: 83.8-99.9) and specificity of 83.3% (95% CI: 65.3-94.4). A significant relationship between CNP and the presence of a centrally located lesion within the thoracic spine was also observed (OR: 155.0 [95% CI lower limit: 16.0]; p<0.0001, 2-tailed Fisher exact test). In all animal models, neurons with bilateral descending projections to the lumbosacral superficial dorsal horn were concentrated in the autonomic IMM nucleus surrounding the mid-thoracic central canal.

Okuda believes that these observations provide the first evidence leading towards identifying the etiology of CNP. These data may not only assist with the development of refined symptomatic therapies, but also allow for insights into unique pain syndromes observed in other demyelinating subtypes; such as neuromyelitis optica (NMO).