Cognitive and Affective Control of Pain in the Human Brain and Brainstem Revealed by Means of Functional MRI and Analyses of Network Connectivity

Abstract

Pain is a complex individual experience that involves sensory/discriminative, motor, autonomic, and cognitive/affective components. Acute pain permeates the human experience, and chronic pain is highly prevalent and costly within our healthcare system. Despite centuries of characterization and research, we have not yet precisely described the neurophysiological mechanisms of pain processing and modulation. The objective of the work contained in this thesis was to further our understanding of the complex temporal relationships and interconnected functions between brain and brainstem regions during the experience of pain and in other sensory or modulated states. Each of three projects employed functional MRI methods to explore related aspects of the sensory, cognitive, and affective dimensions of pain perception and regulation in healthy volunteers. The first study investigated properties of affective pain modulation using previously collected data from music analgesia, mood modulation, and individual differences studies. This work provided a foundational understanding of the powerful effects that cognitive and affective strategies, as well as autonomic homeostatic influence, can exert to continuously alter the way that we experience acute pain. The second study built on this foundation by expanding our connectivity network into cortical regions and limbic structures in order to assess the effects of music analgesia in greater detail. The results of these two studies provided complementary evidence for the complex nature of continuous, active pain modulation, and the influence of our psychological state in engaging the descending modulatory feedback system. The last study aimed to simplify the approach to focus on the sensory/discriminative domain of pain, comparing neural activity across painful and non-painful somatosensory stimuli. Surprisingly, the results showed no group differences in connectivity between stimuli, but individual differences were found based on pain sensitivity and regions associated with cognitive and affective processing. Together, this body of work supports the assertion that healthy pain responses are dependent on our psychological and homeostatic states, which continuously adapt to our environment and provide feedback to neural systems that process sensory integration.