Neural Mechanisms Underlying Modulatory Control of Pain in Multiple Sclerosis

Neuropathic pain is the most common kind of pain in multiple sclerosis (MS). However, it is not easy to understand for those with the diagnosis. This kind of pain differs from everyday headaches or muscle strains and is often hard to describe. It is sometimes described as like a toothache, other times like a burning pain, and sometimes as a very intense sensation of pressure. This type of pain is not caused by a traumatic injury. Rather, when nerves fibers are damaged in MS, they become hypersensitive, and the nerve fibers themselves generate the pain; or when the insulating sheaths around the nerve fibers, called myelin, are damaged in MS, they allow false pain signals to be mistakenly communicated to the brain.

Usually, there are two central nervous system (CNS) mechanisms to modulate pain in healthy people. These two CNS pain modulatory circuits involve small gray matter regions in the lower part of the brain, called brainstem, and those in the spinal cord. However, we do not know much about when and how these pain modulation circuits become dysfunctional in MS patients, partly because of the lack of neuroimaging tools with sufficient resolution to study these small anatomical structures in the brainstem and spinal cord.

Recently, the increasingly wider availability of ultra-high field magnetic resonance imaging (MRI) scanners holds promise to overcome this technical limitation by providing sub-millimeter resolution functional images of the brain and spinal cord. Taking advantage of this technical advance and our expertise in spinal cord imaging, we will explore these brainstem and cervical spinal cord pain modulatory circuits with unprecedented detail using ultra-high field functional MRI in MS patients with neuropathic pain. Furthermore, we will relate the dysfunction of these CNS pain modulatory circuits with nerve fiber tissue damage in MS, using a technique called diffusion MRI, which is sensitive to the loss of nerve fiber tissue integrity.

The proposed study will shed light into the mechanisms underlying the dysfunction of the CNS pain modulation in MS. Better understanding of the modulatory control of pain would eventually lead to new treatments for neuropathic pain relief, such as novel paradigm of electrical stimulation of the spinal cord, and may also serve as a biomarker to test the efficacy of these new treatments.