Chronic Pain Modifies the Cerebral Opioid System

Download or read book Chronic Pain Modifies the Cerebral Opioid System written by Scott Thompson and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The opioid system plays a critical role in both the experience and management of pain. While it is readily apparent that opioid system activation can lead to pain relief, the effects of pain on the opioid system remain opaque. Several clinical studies have demonstrated that chronic pain is associated with opioid receptor availability differences in the brain as compared to healthy controls. However, what this precisely means is unclear. The root of this observation could be anything from a predisposing factor, a transient functional state, a potentially recoverable remodeling of the system or permanent degeneration. Further, it is unknown if the observed differences in the opioid system have any consequential ramifications to the quality of life of individuals with chronic pain. The present work was designed to increase our knowledge of the opioid system changes that occur in the brain as a result of chronic pain. We took the approach of applying a clinical in vivo brain imaging tool (Positron Emission Tomography: PET) to a rodent model of intractable neuropathic pain (Spared Nerve Injury: SNI) allowing for ex vivo tissue assessment (immunohistochemistry) to investigate the molecular basis of the observed in vivo changes. Over a series of studies in this Thesis, a line of reasoning is presented to demonstrate the relevance of our approach as well as a theory on the molecular basis and consequences of chronic pain to the opioid system in the brain. Many interesting secondary findings related to pain, behavior and methodologies are also observed. The work is organized into three studies. In the first study, we investigated if the SNI rat model of neuropathic pain in fact produces ongoing pain, a central characteristic of clinical neuropathic pain. Our data demonstrate brain activity suggestive of ongoing pain. In the second study, we investigated whether or not surgically modifying healthy rats with this pain model would lead to decreased opioid receptor availability as implied by clinical studies. The results found opioid receptor availability decreased in the insula, caudate-putamen and motor cortex. For the final study, tissue from the insula and caudate-putamen underwent ex vivo processing to determine the molecular basis for the observed changes. It was found that mu-opioid receptor down-regulation, as opposed to endogenous ligand binding or neurodegeneration, was the most likely cause of the chronic pain induced changes to the opioid receptor system. Further, anhedonia, a core component of depression, was found to be correlated with mu-opioid receptor expression levels. Given that depression is a common comorbidity to chronic pain, this finding may provide insight into the relationship between these conditions. This series of experiments not only adds to the knowledge of the consequences of chronic pain, but also outlines an approach to taking advantage of in vivo rodent brain imaging. Employing the same imaging method for preclinical work as used for clinical studies creates a translational bridge between the two worlds while giving the researcher access to preclinical tools to extend knowledge. " --