Behavioral and Neural Correlates of Conditioned Pain Modulation in the Human Brainstem and Cervical Spinal Cord Using Functional Magnetic Resonance Imaging
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When one noxious stimulus is coupled with a second noxious stimulus applied to a remote region of the body relative to the first stimulus, the perception of pain is reduced. This phenomenon is termed conditioned pain modulation (CPM) and it’s thought to engage descending inhibitory controls originating in the brainstem which modulate pain processing pathways, resulting in a decrease in pain. This thesis explores the CPM effect in humans, to further our understanding of pain modulation within the central nervous system (CNS). Previous research reveals that CPM evokes pain inhibition in the majority of healthy pain-free individuals, while recent studies have shown that a significant proportion of healthy individuals also demonstrate pain facilitatory responses similar to those exhibited by individuals with chronic pain. Currently, no imaging studies have exclusively explored subcortical changes in activity evoked by the CPM paradigm. Therefore, this thesis delves into uncovering the changes in the brainstem and spinal cord activity in response to the CPM paradigm by investigating the behavioral and neural responses of healthy females using functional magnetic resonance imaging (fMRI). CPM was induced by delivering a heat test stimulus to the right thenar eminence and a cold conditioning stimulus to the left thenar eminence simultaneously, in 25 females aged 27.6 ± 7.82, while obtaining behavioral and imaging data. We found that the CPM paradigm evoked a significant reduction in perceived pain coupled with significantly greater blood oxygenation-level dependent (BOLD) responses in the PAG, RVM, DRt and the DH of the spinal cord, compared to the control condition, where only the heat test stimulus was delivered. Furthermore, the connectivity between these regions was greater during CPM than during the control condition. Lastly, we found significant differences in the behavioral and neural responses between individuals demonstrating pain inhibition and those demonstrating pain facilitation in response to CPM. Furthermore, connectivity findings suggest that different networks are engaged when experiencing an enhanced perception of pain compared to when the pain is reduced during CPM. These findings enhance our current knowledge of the subcortical network involved in CPM, and provide novel insights into the neural correlates of pain modulation.