Abstract Details

Title Central Neuropathic Pain in Multiple Sclerosis Results from Distinct Thoracic Spinal Cord Lesions

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 216

Objective

Background BACKGROUND: Approximately 30-40% of patients with 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.

Design/Methods DESIGN/METHODS: Parallel clinical and neuro-anatomical studies were performed. A clinical investigation of consecutively acquired MS patients with and without CNP within a single MS center was conducted. A multivariate logistic regression model, incorporating significant covariates, was used 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 CTb and fluorescent tracers were performed in three animal species (i.e. rat, cat, monkey).

Results RESULTS: Clinical data were available in MS patients with (n=32; F:23; median age: 34.6y (range:27.4-45.5)) and without (n=30; F22; median age: 36.6y (range: 31.6-47.1)) CNP. The value of a central focus between 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 focus 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 intermediomedial nucleus surrounding the mid-thoracic central canal.

Conclusions CONCLUSIONS: Our observations provide the first evidence for the etiology of CNP. These data may not only assist with the development of refined symptomatic therapies, but allow for insights into unique pain syndromes observed in other demyelinating subtypes (i.e. NMO).

Authors/Disclosures
Darin T. Okuda, MD, FAAN (UT Southwestern Medical Center) PRESENTER	Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cortechs AI. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Okuda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Bioscience. Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Okuda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Zenas BioPharma. The institution of Dr. Okuda has received research support from Novartis. The institution of Dr. Okuda has received research support from Alexion. Dr. Okuda has received intellectual property interests from a discovery or technology relating to health care.
Kara R. Melmed, MD (NYU Langone Neurology Associates)	Dr. Melmed has nothing to disclose.
Robert Flamini, MD	Dr. Flamini has received personal compensation in the range of $0-$499 for serving as a Consultant for Biocodex. Dr. Flamini has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Flamini has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jazz Pharmaceuticals.
	No disclosure on file
	No disclosure on file
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	No disclosure on file

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