Interactions Between Endocannabinoid and Endogenous Opioid Systems Prospectively Influence Postoperative Opioid Use in Pregnant Patients Undergoing Cesarean Delivery
Amanda L Stone 1, Amelie Pham 2, Sarah S Osmundson 2, Alex Pedowitz 3, Philip J Kingsley 4, Larry J Marnett 5, Sachin Patel 6, Nancy Wickersham 7, Laura L Sorabella 1, Stephen Bruehl 1
- 1Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee.
- 2Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee.
- 3Miller School of Medicine, University of Miami, Miami, Florida.
- 4Department of Biochemistry, Vanderbilt University, Nashville, Tennessee; A.B. Hancock Memorial Laboratory for Cancer Research, Vanderbilt University, Nashville, Tennessee.
- 5Department of Biochemistry, Vanderbilt University, Nashville, Tennessee.
- 6Department of Psychiatry, Northwestern University School of Medicine, Chicago, Illinois.
- 7Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Affiliationer
Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This study evaluated the interactive effects of preoperative beta-endorphin (BE) concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol and plasma anandamide) on postoperative opioid use and pain intensity in a prospective cohort of n = 112 pregnant patients undergoing scheduled cesarean delivery. Maternal blood and CSF samples were collected preoperatively for BE and EC assays. Patients completed measures of outpatient opioid use (number of tablets used and days of use) and average pain intensity at 2 weeks postoperatively. Results of general linear model analyses controlling for maternal age, body mass index at time of delivery, and race revealed significant multiplicative interactions between EC and BE concentrations on number of opioid tablets used (based on pill count), days of opioid use, and total milligram morphine equivalents used in the 2-week follow-up period. Elevated preoperative plasma and CSF 2-arachidonoylglycerol predicted reduced outpatient opioid analgesic use, particularly for patients low in CSF BE. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (P < .02) characterized by higher preoperative BE concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma anandamide concentrations. Further exploration of interactions between EC and endogenous opioid inhibitory systems as they influence responses to opioid analgesics in other clinical pain populations may help guide the development of precision pain management approaches. PERSPECTIVE: In the postoperative setting of patients undergoing cesarean delivery, elevated ECs were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in CSF. Further exploration of interactions between these 2 inhibitory systems as they impact responses to pain management interventions appears warranted.
Keywords: Endocannabinoid; Endogenous opioid; beta-endorphin; opioid use; postoperative pain.