Brain Vascular Plasticity in the Context of Peripheral Painful Trauma - The PI proposes a high-impact multidisciplinary research project investigating the effects of brain microvascular anatomy and function on neuronal and glial plasticity in a mouse model of peripheral neuropathy. Chronic pain is a heavy burden for the individual and society, affecting 30% of the adult population in the USA, and presenting with multiple co-morbid psychiatric disorders, including mood alterations and cognitive impairment. One pivotal mechanism that could explain the chronification of pain as well as its resistance to classical treatment is the concept of pain centralization, where initial sensory events can gradually alter the central nervous system, resulting in amplified pain and/or aberrant pain that exists without peripheral sensitization. Alterations in brain circuitry have been well reported across a spectrum of pain conditions, such as complex regional pain syndrome, fibromyalgia, neuropathic pain, and migraine, thus prompting the quest for treatments that could reset these systems. However, most of the research in this area overlooks the evolving brain microvascular changes that may parallel cellular plasticity. Our long-term goal is to delineate brain vascular alterations (permeability, anatomy, and perfusion) and the associated changes in neurons and glia that parallel the progression of peripheral neuropathy. This approach goes beyond attempting to mask the experience of pain via pharmacotherapy (including addictive opioid treatment) and seeks to understand the mechanistic underpinnings of pain chronification via (mal)adaptive brain alterations. Specifically, we aim to 1: Characterize the anatomical and histological signs of blood-brain-barrier permeability following peripheral neuropathy. 2: Identify changes in brain micro-vascularization following peripheral injury. And 3: Characterize the effect of brain vascular plasticity on neuronal and glial abundance and function. While it is understood that pain is a subjective experience that ultimately resides in the brain, there is no characterization of how an injury to the limb causes long-term brain alterations, and for many patients, a lifetime of pain and suffering. This proposal outlines a path by which trauma to peripheral tissues can cause long-lasting behavioral and brain plasticity via vascular mechanisms. This proposal will enhance the infrastructure of research and education at Queens College, introducing biochemical and biomedical research experiences to undergraduate and graduate students. This would allow them to experience a broad spectrum of techniques, and acquire skills such as small animal surgery, behavioral testing, and advanced biochemical analyses.
