A Two-Pronged Approach to Stemming the Opioid Epidemic: Preclinical Strategies for Substance Use Disorder Medications Development and Liquid Biopsy Detection of Inflammatory Pain

The U.S. is in the grips of a public health crisis driven by misuse of psychoactive drugs (e.g., prescription opioids, heroin). In consequence, this has generated a multitude of health issues, including overdoses, deaths and disability, as well as the increased incidence of opioid use disorder (OUD), a condition manifested by escalating physical and psychological impairments. While current FDA-approved OUD medications substantially improve the odds of recovery, the gravity of the opioid crisis demands investigation of novel, more efficacious treatment options. The prevalence of recreational opioid misuse is compounded by excessive prescribing of opioid analgesics. Despite regulatory efforts to mitigate poor prescribing practices, more than 17% of Americans possessed at least one opioid prescription in 2017 with the average number of total opioid prescriptions reaching 3.4 per person. Excess medications are often diverted to friends and family members for recreational use. Pain clinicians are in desperate need of a reliable methodology to quantify pain at the point-of-care to ensure appropriate dose titration required to mitigate the pain experience without overprescribing. The National Institutes of Health (NIH) have launched the Helping to End Addiction Long-Term (HEAL™) Initiative, a massive, multifaceted effort to combat the opioid epidemic. The two primary focus areas of the NIH HEAL™ Initiative Research Plan include “Improving Treatments for Opioid Misuse and Addition” and “Enhancing Pain Management” which contain explicit objectives, such as identifying new targets for OUD treatment and establishing acute and chronic pain signatures, respectively. The studies detailed in this dissertation align with the goals set forth by the HEAL™ Initiative. Our findings demonstrate that the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonist lorcaserin robustly diminishes the reinforcing value of the prescription opioid oxycodone (OxyContin®) and does not possess abuse liability. We also have identified a list of genes associated with high drug relapse vulnerability that should be prioritized as candidates targets for development of SUD medications. Finally, we designed and implemented a proof-of-concept liquid biopsy approach to quantify inflammatory pain with the ultimate goal of enhancing prescribing practices at the point-of-care.

Name thesis:degree_name

Pharmacology and Toxicology (Doctoral)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2021

Author dc:creator

• Merritt, Christina

• Biology, Neuroscience

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12614

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12614