Investigating neural mechanisms of hypersensitivity in chronic pain

PROJECT SUMMARY/ABSTRACT Pain is a complex experience often associated with noxious stimulation. However, for individuals with Chronic Overlapping Pain Conditions (COPCs), the central nervous system can augment or cause pain in the absence of noxious input. Many of these patients have diffuse hyperalgesia (elevated pain responses to noxious stimuli) and allodynia (perception of pain for non-noxious stimuli). Additionally, chronic pain patients are hypersensitive to a variety of sensory stimuli (such as light, odor and sound), suggesting a global impairment in sensory processing. Pain processing in the CNS normally occurs via ascending and descending nociceptive pathways which integrate in several brain areas, including the thalamus, and the cingulate, somatosensory, prefrontal and insular cortices. Importantly, none of the brain regions mentioned above are uniquely associated with the perception of pain, therefore pain most likely involves coordinated activity within a network of brain regions that play a role in pain perception. Studying the brain as a complex network of interconnected regions might provide unique insights to the underlying pathophysiology of chronic centralized pain conditions Our overall objective is to identify neural mechanisms that contribute to sensory hypersensitivity in chronic pain patients. The short-term training goal for the F99 phase is to learn and use quantitative sensory testing and advanced computational methods to measure functional connectivity and network properties of fMRI data. Network analyses will provide novel insights into the interaction of functional brain networks during sensory processing that contribute to visual hypersensitivity. My dissertation work (Research Aims 1 & 2) along with the training plan will provide evidence for the functional relationship between pain and visual processing areas. This offers a foundational premise for the long-term goal, to be completed during the K00 phase, which is to utilize multimodal imaging to investigate casual interactions between brain areas involved in pain and sensory processing that contribute to hypersensitivity in chronic pain.