Abstract
Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.
Highlights
Reviewed by: Andrew David Gaudet, University of Texas at Austin, United States Kate Lykke Lambertsen, University of Southern Denmark, Denmark
It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in Multiple Sclerosis (MS)
This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective tumor necrosis factor α (TNFα)-targeting pain therapies
Summary
Multiple Sclerosis (MS) is an autoimmune disease characterized by aberrant immune cell activity leading to inflammation and demyelinating lesions of central nervous system (CNS) [1,2,3]. The MS disease course can follow multiple trajectories. Primary progressive disease worsens steadily from onset. Progressive relapsing disease increasingly worsens but with some relapsing and remitting characteristics, meaning there are periods where symptoms worsen, improve again. Most patients have a biphasic disease course, wherein they initially present with a relapsing-remitting phenotype, but as the disease progresses there is a switch to the secondary progressive phenotype and disability continually worsens [2, 5]. There are numerous symptoms and comorbidities associated with MS, which can affect sensory, motor, and cognitive modalities. One of the most debilitating ailments experienced by MS patients is chronic pain [6, 7]
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