Microglia Activation in Neuropathic Pain During MS: Possible Therapeutic Target
Abstract
Multiple sclerosis (MS) is a demyelinating disease associated with an inflammatory immune response in the central nervous system (CNS). MS patients can experience either relapsing-remitting symptoms or progressive symptoms of disease; however, the severity of disease can vary among patients. Common symptoms in MS patients include visual impairment, limb weakness, fatigue, limb spasticity, cognitive dysfunction, and pain. Nearly 50% of MS patients report having chronic neuropathic pain symptoms. Neuropathic pain is associated with sensory abnormalities and altered responses to stimulus, and loss of sensation in some areas. Neurons are directly responsible for the transmission and perception of pain. Microglia are the resident immune cells of the CNS, but they actively communicate with neurons. Microglia have been shown to be activated in the CNS during demyelinating disease and activated microglia have been shown to be present in demyelinating lesions in the brain and spinal cord of MS patients. Activation of microglia has been implicated in the development and maintenance of neuropathic pain. Therefore, we propose that chronic activation of microglia plays an important role in development and maintenance of neuropathic pain during MS. We further propose that reducing microglia activation with a newly synthesized compound that reduces microglia activation will reduce neuropathic pain during MS. These are the first studies focused on determining the role of microglia in neuropathic pain during MS. The studies will use two mouse models for MS that represent two different clinical disease types, chronic progressive disease and relapsing-remitting disease. The proposed studies will determine how microglia activation contributes to neuropathic pain during demyelinating disease. Most importantly, these studies will determine whether a therapy directed at reducing microglia activation leads to reduced neuropathic pain during demyelinating disease. Many MS patients have symptoms of neuropathic pain for which there are no effective treatments. We propose to examine a newly synthesized compound directed against activated microglia for treatment of neuropathic pain. Several preclinical studies have already been conducted on the compound to assess dosage, administration route, tolerance, and addiction; thus, this compound would require minimal additional preclinical studies before entering clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710081
Entities
People
- Julie Olson
Organizations
- United States Army
- University of Minnesota