One of the most urgent problems in the United States is the steadily increasing numbers of overdose deaths related to opioid use. Opioids are addictive drugs that have a complicated place in society due to their medical use as well as their misuse and abuse. Opioids are appropriately used for the treatment of acute pain that results from trauma or surgical procedures as well as for management of cancer pain. The use of opioids for chronic, non-malignant pain, however, is increasingly regarded as a dangerous option with evidence increasingly suggesting that overall harm may out-weigh possible benefits for many patients. The duration of exposure to opioids is directly related to the risks of development of addiction. The circuits mediating the addictive and analgesic actions of opioids are largely overlapping. Effective non-addictive options to treat some types of pain remain a major unmet medical need.

The mission of the Center of Excellence in Addiction Studies (CEAS) at the University of Arizona is to advance research into underlying brain mechanisms that promote opioid addiction and relapse through the lens of the pain experience. Addiction and relapse are characterized by dysregulation of brain circuitry that involves diminished activity of brain reward circuits, increased responsiveness of stress circuits and impaired functioning of executive cortical circuits. Neural changes are observed in the basal ganglia, extended amygdala and prefrontal cortical regions and encompass a wide range of endogenous neurotransmitters including dopamine, opioid peptides, endocannabinoids, corticotropin releasing factor (CRF), dynorphin, glutamate and others. While chronic pain and addiction are different disorders, there is a remarkable overlap between the influence of drugs of abuse and chronic pain on these circuits. The intersection of pain and addiction could be the source for rational design of pharmaceutical interventions that ameliorate substance abuse disorders and contribute to the resolution of the opioid crisis.

The CEAS at the University of Arizona is composed of 8 faculty members from within the Departments of Pharmacology, Psychology and Chemistry/Biochemistry. Our investigators have broad expertise in evaluation of mechanisms that underlie the maladaptation in brain circuits relevant to pain and addiction. Ongoing topics of interest to CEAS investigators includes:

• Intersection of pathways mediating pain, stress and reward
• Role of endogenous opioids in pain and stress
• Descending pain modulatory circuits
• Testing novel compounds at new, and well known, molecular targets 
• Behavioral signs of reward. 
• Regulation of the reward pathway in the absence and presence of opioids
• In vivo microdialysis and HPLC-MS to measure endogenous cannabinoids
• Novel mechanisms to reduce CNS inflammation and pain 
• Neural ensemble activity and dopamine during behavior and sleep 
• Cellular analysis of neurotransmitter release in cell lines, to neurons and in vivo.
• Electrical brain stimulation for neural coordination, plasticity, and learning. 
• Neural oscillations in learning, memory, disease and aging. 
• Electroanalytical methods and software for in vivo analysis of neurotransmitters
• Novel methods to elucidate tonic and phasic dopamine signaling dynamics. 
• Development of conducting polymer films for direct biosensing.
• Simultaneous in vivo electrophysiology at electrode arrays with electrochemistry 
• New peptide synthesis methods
• Bifunctional peptide agonist and antagonist probes 
• Efficient methodologies for improvement of bioactivity and bioavailability
• Ligands to overcome multi-variable pain and pathological plasticity
• Combined opioid/neurokinin pharmacology to reduce opioid reward
• Physiology underlying craniofacial and cancer induced bone pain
• Sex dependent hormonal modulation of pain
• Antinociceptive and pronociceptive mu and kappa opioid circuits
• Mesolimbic and cortical circuits encoding pain aversiveness
• Cellular regulation of opioid receptors and drug discovery
• CRF regulation of VTA dopamine neurons 
• Relapse to drug seeking

The CEAS offers opportunities for other investigators at University of Arizona as well as other Universities in Arizona and in other parts of the Southwest including New Mexico and parts of Texas. The CEAS is committed to promoting increased diversity in addiction research by recruiting investigators and students from under-represented populations in to engage in addiction research. A significant impact of the CEAS will be to leverage established funding to develop new research on addiction research. In addition, the impact of funds from the CEAS will be amplified by interactions with the Comprehensive Center of Pain and Addiction.