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

    Pham, Amelie / Osmundson, Sarah S / Pedowitz, Alex / Wickersham, Nancy / Sorabella, Laura L / Bruehl, Stephen

    Research square

    2023  

    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 uid (CSF) levels of the analgesic ...

    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 uid (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 uid 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 uid β-Endorphin levels were only weakly correlated with plasma β-Endorphin levels (r = 0.30, p < .01). Preoperative cerebrospinal uid and plasma β-Endorphin levels were both positively associated with postpartum pain measures (cerebrospinal uid: 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 uid 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.
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3125641/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interactions Between Endocannabinoid and Endogenous Opioid Systems Prospectively Influence Postoperative Opioid Use in Pregnant Patients Undergoing Cesarean Delivery.

    Stone, Amanda L / Pham, Amelie / Osmundson, Sarah S / Pedowitz, Alex / Kingsley, Philip J / Marnett, Larry J / Patel, Sachin / Wickersham, Nancy / Sorabella, Laura L / Bruehl, Stephen

    The journal of pain

    2024  , Page(s) 104548

    Abstract: 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 concentrations ( ... ...

    Abstract 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 concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol [2-AG] and plasma anandamide [AEA]) 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 beta-endorphin 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, BMI at time of delivery, and race revealed significant multiplicative interactions between EC and beta-endorphin 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-AG predicted reduced outpatient opioid analgesic use particularly for patients low in CSF beta-endorphin. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (p<.02) characterized by higher preoperative beta-endorphin concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma AEA 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 development of precision pain management approaches. PERSPECTIVE: In the postoperative setting of patients undergoing cesarean delivery, elevated endocannabinoids were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in cerebrospinal fluid. Further exploration of interactions between these two inhibitory systems as they impact on responses to pain management interventions appears warranted.
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2018789-0
    ISSN 1528-8447 ; 1526-5900
    ISSN (online) 1528-8447
    ISSN 1526-5900
    DOI 10.1016/j.jpain.2024.104548
    Database MEDical Literature Analysis and Retrieval System OnLINE

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