Prospective evaluation of cerebrospinal fluid levels of β-Endorphin as a predictor of opioid use after scheduled cesarean delivery

Abstract

Abstract Background Prior laboratory work indicates that lower endogenous opioid function is associated with greater analgesic and subjective responses to opioid analgesics. We evaluated whether lower preoperative cerebrospinal fluid (CSF) levels of the analgesic endogenous opioid β-Endorphin (BE) were associated with increased opioid use after cesarean delivery (CD). Methods We enrolled 136 pregnant women without opioid use or chronic pain who were undergoing CD under regional anesthesia. Preoperatively, participants completed validated pain measures and biospecimens were collected to assess BE levels in plasma and CSF. Postoperatively, pain measures at 48 hours and 2 weeks postpartum were assessed. We evaluated the association between CSF BE levels and total opioid use (in morphine milligram equivalents; MMEs) using linear regression controlling for confounding factors (primary analysis). In secondary analyses, we examined: 1) associations between plasma BE levels and total opioid use, and 2) associations between CSF and plasma BE levels and secondary outcomes (inpatient versus outpatient opioid use, pain intensity). Results Participants completed surveys with 100% response rate. The majority were non-Hispanic white (65%), college educated (58%), had private insurance (71%), and had a prior cesarean delivery (69%). Psychiatric diagnoses (depression or anxiety) were common, both currently (22%) and in the past (26%).The median total opioid use across the inpatient and 2-week postpartum follow-up period was 89.1 milligram morphine equivalents (IQR 25–138). Preoperative cerebrospinal fluid β-Endorphin levels were not associated with total opioid use (beta = -0.05, SE 0.45, p = 0.64). Similar findings were noted for plasma β-Endorphin levels. cerebrospinal fluid β-Endorphin levels were only weakly correlated with plasma β-Endorphin levels (r = 0.30, p < .01). Preoperative cerebrospinal fluid and plasma β-Endorphin levels were both positively associated with postpartum pain measures (cerebrospinal fluid: at 48 hours, beta = 0.19, SE 0.16, p < 0.05; Plasma: at 48-hours, beta = 0.02, SE 0.03, p = 0.02, and at 2-weeks, beta = 0.27, SE 0.03, p < 0.01). Conclusions Lower preoperative cerebrospinal fluid levels of β-Endorphin are not associated with increased opioid analgesic use after scheduled cesarean delivery. It is possible that unassessed variability in baseline opioid receptor sensitivity may have confounded ability to test associations between β-Endorphin levels and opioid use outcomes.