Dopamine Deficiency Predicts Pain: Toward A Novel Framework for the Neurophysiological Classification and Treatment of Chronic Pain
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2022
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Bi-College (Haverford and Bryn Mawr Colleges). Neuroscience Program
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eng
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Dark Archive until 2027-01-01, afterwards Open Access.
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Abstract
Chronic pain is a widespread issue which strips millions of people of their agency, and bears devastating and often debilitating lifelong consequences for mental and physical wellbeing. It is also one of the largest burdens on socioeconomic welfare, costing the United States government an estimated $635 billion each year in medical expense and lost productivity. Although its pathophysiological mechanisms are far from elucidated, research spanning the past several decades has revealed a number of significant neurobiological correlates and theoretical frameworks which have yet to escape the enclosure of scientific journals to enter both the clinic and public awareness. It is generally accepted that the treatment of chronic pain is somewhat of a medical conundrum, with few chronic pain patients experiencing long-term relief, and many encountering interpersonal frustration and systemic roadblocks in clinical care. In line with chronic pain's status as a public health crisis, a great deal of literature highlights the urgency for new targets in pain management and prevention. Many published studies and institutional reports even provide detailed protocol for the implementation of higher-efficacy treatment methods for a wide array of conditions. In other words, there already exists a substantial pool of scientific insight which, if extended to translational research, could decrease morbidity and improve quality of life for many individuals, some of whom may be suffering unnecessarily or excessively, in a medical system that cannot provide for their clinical needs, often prescribing treatments designed for acute injuries to those who live for years with an elusive chronic syndrome. As a result, people's lives are excessively devastated by pain conditions which could be better managed, mitigated, or entirely prevented. Among scattered literature originating from a range of perspectives, one set of relationships emerges as critically important, with expansive implications for many areas of pain research, as well as for those who suffer with chronic pain. However, these disparate findings are yet to be integrated, and are therefore largely unknown, and alarmingly under-researched. A close examination of decades of research that has remained largely under the radar reveals a significant contribution of the state of dopaminergic neurotransmission to the mechanisms which underlie pain chronification. This comprehensive review synthesizes research in pharmacology, neurophysiology, psychiatry, and etiology in an effort to delineate the evidence for dopamine dysfunction as a common mechanism in the development of chronic pain. This includes documentation of correlational data revealing its prevalence, neurophysiological findings demonstrating its essential role in the homeostasis of pain-processing circuitry, as well as clinical evidence of the pervasive downstream effects and predispositions consistently observed with an imbalance of this system. By triangulating a number of neurophysiological mechanisms which are rarely considered in tandem, this paper highlights a critical shortcoming in the current literature on chronic pain. Integration of this widely overlooked research ultimately points to significant new targets for the clinical intervention, prevention, and reversal of chronic pain conditions, under a novel framework which could advance the current understandings about the fundamental nature of pain.