Lowering Pathologic TNF Levels Exclusively Within the Brain Rapidly Alleviates Long-Standing Injury-Induced Neural Pathologies

It is well known that injuries to the brain can result in a decreased quality of life, waning interactions with others, and overall patient disability, even to the point of not being able to perform one's daily living activities. Along with other pathologies, a primary component to traumatic brain injury (TBI) is chronic debilitating pain, termed neuropathic pain. This type of chronic pain is a poorly treated disorder related to long-term harmful cellular and behavioral changes, consequently requiring an innovative breakthrough therapy. Major therapy for acute and chronic pain is opioids. While opioids affect acute pain, their effect is limited and can be dangerous for chronic pain. In fact, the continued use of opioids for chronic pain has created a national emergency of opioid addiction and excess mortality, warranting a change in current therapy. Chronic neuropathic pain, as with numerous forms of injury, is associated with an inflammatory response. In particular, it is unchecked inflammatory responses that orchestrate the onset, development, and maintenance of chronic pain. Thus, chronic pain has a fundamental persistent inflammatory component that culminates in disabilities and impairment, as well as comorbid disease onset. Spread of inflammation along the neuroaxis is postulated as underlying the chronicity of pain. The transfer of pain to sites distant to that of the initial site of injury (for example, stroke resulting in chronic shoulder pain) may exist as a result of conveyance of cytokines, such as tumor necrosis factor- α (TNF α ), IL-1β, and IL-6, along the neuroaxis or of enhanced cytokine signaling [1].