Hypothalamic Pathophysiology in the Neuroimmune,Dysmetabolic and Longevity Complications of Chronic Opiate Dependency

 Hypothalamic Pathophysiology in the Neuroimmune,Dysmetabolic and Longevity Complications of Chronic Opiate Dependency

New conceptual and therapeutic advances in our understanding of various important pathophysiological states have remarkable relevance to current practices in the area of the treatment of opiate dependence. Major breakthroughs have recently occurred in our understanding of: The central mediation of the hypertensive-obesity-metabolic syndrome and particularly its association with the hypothalamic regulation of longevity; The ability of addictive chemical species to induce local inflammation of many parts of the CNS including the hypothalamus; The interactions between the host and the resident gut microbial flora and its implications for systemic organismal health and disease. These breakthroughs have occurred on the backdrop of detailed quantified pathophysiological and mortality surveys of opiate dependence from several continents and in the context of exciting new pharmacological developments including suppressors of central neuroinflammation such as ibudilast, non-habituating newer generation opiates such as PTI-609, and depot-implantable forms of the opiate antagonist naltrexone. Opiates induce electrical silencing of POMC neurons resulting in hyperphagic obesity and dysmetabolic syndrome, mimicking senescence. Hence POMC neuronal pathophysiology becomes amplified organism-wide in a feed-forward loop. Together these factors suggest that we are on the very threshold of new insights which have the potential to overhaul both our conceptual understandings and our clinical treatments. The purpose of this review is to bring together findings from widely disparate areas and to elucidate their relevance and overlap with research on the effects of long-term opiate dependence. Whilst opiate dependence is the primary focus these observations likely also pertain to other chemical dependencies.