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chronic pain dopamine homeostasis dopaminergic signaling hyperalgesia hypodopaminergia opioid analgesics precision transmodulation Introduction In 2020, the United States experienced an average of 44 deaths daily due to prescription opioid overdoses, resulting in more than 16,000 fatalities that year alone.1 Nearly a quarter (24%) of all overdose deaths that year were related to prescription opioids, indicating a 16% increase in prescription opioid-related morbidity from 2019 to 2020