The mechanisms leading to opioid tolerance or dependence are not well understood and there are currently no biomarkers for predicting who is at risk for development of OUD. The purpose of this project is to support the feasibility of detecting a miRNA bio-behavioral signature of opioid misuse risk that will demonstrate improved predictive precision compared to current tools such as polygenic risk scores (PRS). Specifically, the study will address key goals of the Wellcome Leap program to develop scalable measures assessing individual addiction susceptibility and quantifying addiction risk and progression during prescription drug use. The study will utilize behavioral, genomics, and bioinformatics pipelines to characterize opioid-induced miRNA expression dynamics among trauma and surgical patients prescribed opioids at discharge. Based on results from this study, the research will develop a high-throughput screening assay to predict risk for opioid use disorder (OUD). The hypothesis is that miRNAs will serve as powerful bio-signatures for predicting long-term clinical outcomes in patients treated with opioids for pain management following trauma injury and/or surgery.

The mechanisms leading to opioid tolerance or dependence are not well understood and there are currently no biomarkers for predicting who is at risk for development of OUD. The purpose of this project is to support the feasibility of detecting a miRNA bio-behavioral signature of opioid misuse risk that will demonstrate improved predictive precision compared to current tools such as polygenic risk scores (PRS). Specifically, the study will address key goals of the Wellcome Leap program to develop scalable measures assessing individual addiction susceptibility and quantifying addiction risk and progression during prescription drug use. The study will utilize behavioral, genomics, and bioinformatics pipelines to characterize opioid-induced miRNA expression dynamics among trauma and surgical patients prescribed opioids at discharge. Based on results from this study, the research will develop a high-throughput screening assay to predict risk for opioid use disorder (OUD). The hypothesis is that miRNAs will serve as powerful bio-signatures for predicting long-term clinical outcomes in patients treated with opioids for pain management following trauma injury and/or surgery.

The specific aim is to develop a new conceptual framework to validate DNA< mRNA, and miRNAs as biomarkers of persistent opioid use among patients after traumatic injury and/or surgery.

The primary goal is to correlate patterns in miRNA sequencing with persistent opioid use after trauma/surgery.

The study will recruit up to 100 adult (>18 yo) participants prospectively from UC Health sites, including Jacobs Medical Center, Hillcrest Hospital, McGrath Outpatient Pavilion, and Koman Outpatient Pavilion. Eligible participants will be identified by reviewing newly admitted patients in the trauma service and/or surgical suite (same day as surgery preoperatively).

The study will collect baseline data including baseline clinical and demographic data, pain/opioid use from surveys/questions, social determinants of health (from survey), and biospecimens (blood for DNA and miRNA sequencing). Data will be collected initially near estimated hospital discharge (baseline), at 7 days post-discharge, 1 month post-discharge, 3 months post-discharge and 6 months post-discharge.

The proposed project will identify a miRNA signature associated with risk for persistent opioid use (defined as ongoing opioid use at 1, 3 and 6 months after index time point) in patients following exposure to opiate medication after traumatic injury/surgery. It is expected to demonstrate improved predictive precision with the miRNA signature compared to current tools alone (PRS, ORT). Success of this project will provide the go signal for a subsequent implementation study to develop a miRNA test kit and optimize the use of this screening tool and its potential to inform targeted interventions to prevent persistent opioid use and OUD after traumatic injury/surgery.

Inclusion Criteria:

• Patients 18 years of age or older
• Patients admitted for traumatic injury at Hillcrest or Jacobs Medical Center or patients who will undergo the orthopedic (e.g., joint, spine), abdominal, breast, vascular (e.g., amputation), or thoracic surgery.

Exclusion Criteria:

• Patients with a prior history of opioid use disorder or dependence
• Pregnant women
• Prisoners
• Patients with an inability to independently provide informed consent to participate in the study due to lack of capacity. This lack of capacity can be from either a chronic/continuous condition (i.e. dementia), or can be temporary (i.e. clear signs of intoxication at the time of the visit (not alert or oriented, slurring words [and confirmed not to be baseline], unsteady gait [and confirmed not to be baseline], or appears impaired based on clinical judgement by PI/Co-I)).

We will recruit up to 100 participants prospectively from UC Health sites, including Jacobs Medical Center, Hillcrest Hospital, McGrath Outpatient Pavilion, and Koman Outpatient Pavilion. Eligible participants will be identified by reviewing newly admitted patients in the trauma service and/or surgical suite (same day as surgery preoperatively).