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American Journal of Public Health Aug 2021Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been... (Review)
Review
Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners' clinical guidelines. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants' attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Community-based OEND programs should be implemented widely in high-risk populations.
Topics: Health Education; Humans; Naloxone; Narcotic Antagonists; Opiate Overdose; Public Health; Systematic Reviews as Topic
PubMed: 34214412
DOI: 10.2105/AJPH.2021.306306 -
HPB : the Official Journal of the... Jul 2022Improved post-operative outcomes have been demonstrated in gastrointestinal procedures where a narcotic sparing strategy has been utilized. Data for... (Review)
Review
BACKGROUND
Improved post-operative outcomes have been demonstrated in gastrointestinal procedures where a narcotic sparing strategy has been utilized. Data for pancreaticoduodenectomy (PD) patients is limited. This study reviews an institutional database for outcomes based on initial analgesic strategy.
METHODS
1004 consecutive patients who underwent PD at Emory University between 2010 and 2017, were included in the analysis. Patients were divided into groups based on primary analgesic strategy employed: epidural alone (EPI), patient controlled opiate analgesia (PCA), dual (dual-PCA/EPI) and other (non-PCA/EPI). Postoperative outcomes for each group were analyzed utilizing univariate and multivariate linear regression.
RESULTS
448 (44.6%) patients were treated with EPI, 300 (29.9%) were given a PCA, 78 (7.8%) had dual-PCA/EPI and 178 (17.7%) had non-PCA/EPI analgesia. On univariate analysis, increased BMI (p = 0.030), PCA use (p < 0.001), venous thromboembolism (VTE) (p < 0.001), post-operative pancreatic fistula (POPF) (p < 0.001) and Ileus/delayed gastric emptying (DGE) (p < 0.001) were all correlated with increased LOS. On multivariate linear regression, VTE (b-coefficient 9.07, p = 0.004) POPF (8.846, p = 0.001), Ileus/DGE (4.464, p = 0.004) and PCA use (1.75, p = 0.003) were associated with significantly increased LOS.
CONCLUSION
A primary narcotic sparing strategy is associated with a significantly reduced LOS and lower rates of Ileus/DGE. Mean opiate usage was significantly lower in the EPI and non-EPI/PCA groups.
Topics: Analgesics; Gastric Emptying; Gastroparesis; Humans; Ileus; Narcotics; Opiate Alkaloids; Pancreaticoduodenectomy; Postoperative Complications; Risk Factors; Venous Thromboembolism
PubMed: 35151580
DOI: 10.1016/j.hpb.2021.12.006 -
The Journal of Pharmacology and... Sep 2021There are no Food and Drug Administration-approved medications for cocaine use disorder, including relapse. The -opioid receptor (MOPr) partial agonist buprenorphine...
There are no Food and Drug Administration-approved medications for cocaine use disorder, including relapse. The -opioid receptor (MOPr) partial agonist buprenorphine alone or in combination with naltrexone has been shown to reduce cocaine-positive urine tests and cocaine seeking in rodents. However, there are concerns over the abuse liability of buprenorphine. Buprenorphine's partial agonist and antagonist activity at the nociception receptor (NOPr) and -opioid receptor (KOPr), respectively, may contribute to its ability to inhibit cocaine seeking. Thus, we hypothesized that a buprenorphine derivative that exhibits antagonist activity at MOPr and KOPr with enhanced agonist activity at the NOPr could provide a more effective treatment. Here we compare the pharmacology of buprenorphine and two analogs, BU10119 and BU12004, in assays for antinociception and for cocaine- and stress-primed reinstatement in the conditioned place preference paradigm. In vitro and in vivo assays showed that BU10119 acts as an antagonist at MOPr, KOPr, and -opioid receptor (DOPr) and a partial agonist at NOPr, whereas BU12004 showed MOPr partial agonist activity and DOPr, KOPr, and NOPr antagonism. BU10119 and buprenorphine but not BU12004 lessened cocaine-primed reinstatement. In contrast, BU10119, BU12004, and buprenorphine blocked stress-primed reinstatement. The selective NOPr agonist SCH221510 but not naloxone decreased cocaine-primed reinstatement. Together, these findings are consistent with the concept that NOPr agonism contributes to the ability of BU10119 and buprenorphine to attenuate reinstatement of cocaine-conditioned place preference in mice. The findings support the development of buprenorphine analogs lacking MOPr agonism with increased NOPr agonism for relapse prevention to cocaine addiction. SIGNIFICANCE STATEMENT: There are no Food and Drug Administration-approved medications for cocaine use disorder. Buprenorphine has shown promise as a treatment for cocaine relapse prevention; however, there are concerns over the abuse liability of buprenorphine. Here we show a buprenorphine analogue, BU10119, which lacks -opioid receptor agonism and inhibits cocaine-primed and stress-primed reinstatement in a conditioned place-preference paradigm. The results suggest the development of BU10119 for the management of relapse to cocaine seeking.
Topics: Buprenorphine; Cocaine; Naltrexone; Receptors, Opioid, mu
PubMed: 34183434
DOI: 10.1124/jpet.121.000524 -
Rural and Remote Health 2015Opioid abuse has reached epidemic levels. Evidence-based treatments such as buprenorphine maintenance therapy (BMT) remain underutilized. Offering BMT in primary care... (Review)
Review
INTRODUCTION
Opioid abuse has reached epidemic levels. Evidence-based treatments such as buprenorphine maintenance therapy (BMT) remain underutilized. Offering BMT in primary care settings has the potential to reduce overall costs of care, decrease medical morbidity associated with opioid dependence, and improve treatment outcomes. However, access to BMT, especially in rural areas, remains limited. This article will present a review of barriers to adoption of BMT among family physicians in a primarily rural area in the USA.
METHODS
An anonymous survey of family physicians practicing in Vermont or New Hampshire, two largely rural states, was conducted. The survey included both quantitative and qualitative questions, focused on BMT adoption and physician opinions of opioids. Specific factors assessed included physician factors, physicians' understanding of patient factors, and logistical issues.
RESULTS
One-hundred and eight family physicians completed the survey. Approximately 10% were buprenorphine prescribers. More than 80% of family physicians felt they regularly saw patients addicted to opiates. The majority (70%) felt that they, as family physicians, bore responsibility for treating opiate addiction. Potential logistical barriers to buprenorphine adoption included inadequately trained staff (88%), insufficient time (80%), inadequate office space (49%), and cumbersome regulations (37%). Common themes addressed in open-ended questions included lack of knowledge, time, or interest; mistrust of people with addiction or buprenorphine; and difficult patient population.
CONCLUSIONS
This study aims to quantify perceived barriers to treatment and provide insight expanding the community of family physicians offering BMT. The results suggest family physicians are excellent candidates to provide BMT, as most report regularly seeing opioid-addicted patients and believe that treating opioid addiction is their responsibility. Significant barriers remain, including inadequate staff training, lack of access to addiction experts, and perceived efficacy of BMT. Addressing these barriers may lower resistance to buprenorphine adoption and increase access to BMT in rural areas.
Topics: Buprenorphine; Confidentiality; Female; Health Knowledge, Attitudes, Practice; Health Services Accessibility; Humans; Inservice Training; Male; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Perception; Physicians, Family; Practice Patterns, Physicians'; Primary Health Care; Time Factors; Trust
PubMed: 25651434
DOI: No ID Found -
Molecules (Basel, Switzerland) Jan 2022Drug abuse still represents a global problem, and it is associated with an increased risk of diseases, injuries, and deaths. Cocaine (COC) and opiates are the most...
Drug abuse still represents a global problem, and it is associated with an increased risk of diseases, injuries, and deaths. Cocaine (COC) and opiates are the most abused drugs and account for a significant number of fatalities. Therefore, it is important to develop methods capable of effectively identifying and quantifying these substances. The present study aims to evaluate the long-term stability of COC, ecgonine methylester (EME), benzoylecgonine (BEG), cocaethylene (COET), norcocaine (NCOC), morphine (MOR), codeine (COD) and 6-monoacetylmorphine (6-MAM) in oral fluid samples. The analytes of interest were isolated from the matrix (50 µL) using the dried saliva spots (DSS) sampling approach and were subsequently analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The parameters that could influence the stability of the target compounds were studied, and these were storage temperature, light, use of preservatives (and respective concentrations), and time. The effects of each parameter were evaluated using the design of experiments (DOE) approach. The stability of the target analytes was improved when the DSS were stored at room temperature, in the presence of light and using 1% sodium fluoride. The best conditions were then adopted for the DSS storage and long-term stability was assessed. COD was only stable for 1 day, EME was stable for 3 days, COC, COET, NCOC and 6-MAM were stable for 7 days, MOR for 14 days and BEG remained stable throughout the study (136 days). This is the first study that evaluates the stability of these compounds in oral fluid samples after application in DSS cards, and optimizes the conditions in order to improve their stability.
Topics: Cocaine; Gas Chromatography-Mass Spectrometry; Narcotics; Opiate Alkaloids; Saliva; Tandem Mass Spectrometry
PubMed: 35163906
DOI: 10.3390/molecules27030641 -
The Journal of Pharmacology and... Aug 2021Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the...
Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the effects of high efficacy opioids, and minimize opioid-cravings while being safe and accessible to a diverse patient population. Although current OUD pharmacotherapies inhibit the euphoric effects of opioids of abuse, the extent to which they safely alleviate withdrawal and opioid-cravings corresponds with their intrinsic opioid receptor (MOR) efficacy. In addition to inhibiting the euphoric effects of opioids of abuse, the medium efficacy MOR agonist buprenorphine alleviates withdrawal and opioid-cravings, but its intrinsic MOR efficacy is sufficient such that its utility is limited by abuse and safety liabilities. Although the MOR antagonist naltrexone minimizes euphoria and has no abuse liability, it exacerbates suffering associated with withdrawal and opioid cravings. Therefore, a therapeutic with intrinsic MOR activity between the partial agonist (buprenorphine) and the antagonist (naltrexone) would strike a balance between the benefits and liabilities of these two therapeutics. To address this need, we derived RM1490, an MOR agonist based on a nonmorphinan scaffold that exhibits approximately half the intrinsic MOR efficacy of buprenorphine. In a series of preclinical assays, we compared RM1490 with buprenorphine and naltrexone at doses that achieve therapeutic levels of central nervous system MOR occupancy. RM1490 exhibited a behavioral profile consistent with reduced reward, dependence, and precipitated withdrawal liabilities. RM1490 was also more effective than buprenorphine at reversing the respiratory depressant effects of fentanyl and did not suppress respiration when combined with diazepam. SIGNIFICANCE STATEMENT: In preclinical studies, RM1490 has a physiological and behavioral profile suitable for opioid use disorder maintenance therapy.
Topics: Buprenorphine; Naltrexone; Opioid-Related Disorders
PubMed: 34011529
DOI: 10.1124/jpet.120.000214 -
JAMA Network Open Apr 2022Given that COVID-19 and recent natural disasters exacerbated the shortage of medication for opioid use disorder (MOUD) services and were associated with increased opioid...
IMPORTANCE
Given that COVID-19 and recent natural disasters exacerbated the shortage of medication for opioid use disorder (MOUD) services and were associated with increased opioid overdose mortality, it is important to examine how a community's ability to respond to natural disasters and infectious disease outbreaks is associated with MOUD access.
OBJECTIVE
To examine the association of community vulnerability to disasters and pandemics with geographic access to each of the 3 MOUDs and whether this association differs by urban, suburban, or rural classification.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study of zip code tabulation areas (ZCTAs) in the continental United States excluding Washington, DC, conducted a geospatial analysis of 2020 treatment location data.
EXPOSURES
Social vulnerability index (US Centers for Disease Control and Prevention measure of vulnerability to disasters or pandemics).
MAIN OUTCOMES AND MEASURES
Drive time in minutes from the population-weighted center of the ZCTA to the ZCTA of the nearest treatment location for each treatment type (buprenorphine, methadone, and extended-release naltrexone).
RESULTS
Among 32 604 ZCTAs within the continental US, 170 within Washington, DC, and 20 without an urban-rural classification were excluded, resulting in a final sample of 32 434 ZCTAs. Greater social vulnerability was correlated with longer drive times for methadone (correlation, 0.10; 95% CI, 0.09 to 0.11), but it was not correlated with access to other MOUDs. Among rural ZCTAs, increasing social vulnerability was correlated with shorter drive times to buprenorphine (correlation, -0.10; 95% CI, -0.12 to -0.08) but vulnerability was not correlated with other measures of access. Among suburban ZCTAs, greater vulnerability was correlated with both longer drive times to methadone (correlation, 0.22; 95% CI, 0.20 to 0.24) and extended-release naltrexone (correlation, 0.15; 95% CI, 0.13 to 0.17).
CONCLUSIONS AND RELEVANCE
In this study, communities with greater vulnerability did not have greater geographic access to MOUD, and the mismatch between vulnerability and medication access was greatest in suburban communities. Rural communities had poor geographic access regardless of vulnerability status. Future disaster preparedness planning should match the location of services to communities with greater vulnerability to prevent inequities in overdose deaths.
Topics: Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Health Services Accessibility; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; United States; COVID-19 Drug Treatment
PubMed: 35438757
DOI: 10.1001/jamanetworkopen.2022.7028 -
The Cochrane Database of Systematic... Nov 2020The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013.
OBJECTIVES
To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances.
SEARCH METHODS
We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate-quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low-quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;-530.00 g, 95%CI -662.78 to -397.22 (one study, 19 particpants) and MD: -215.00 g, 95%CI -238.93 to -191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low-quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI -0.03 to 0.03, two studies,163 participants, low-quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low-quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low-quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low-quality evidence). Methadone versus slow-release morphine: There were no dropouts in either treatment group. Oral slow-release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low-quality evidence). In the comparison between methadone and slow-release morphine, no side effects were reported for the mother. In contrast, one child in the methadone group had central apnoea, and one child in the morphine group had obstructive apnoea (low-quality evidence).
AUTHORS' CONCLUSIONS
Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid-dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow-release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.
Topics: Birth Weight; Buprenorphine; Delayed-Action Preparations; Female; Humans; Infant; Infant, Newborn; Methadone; Morphine; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic
PubMed: 33165953
DOI: 10.1002/14651858.CD006318.pub4 -
The Cochrane Database of Systematic... Feb 2020Medical treatment and detoxification from opiate disorders includes oral administration of opioid agonists. Dihydrocodeine (DHC) substitution treatment is typically low... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medical treatment and detoxification from opiate disorders includes oral administration of opioid agonists. Dihydrocodeine (DHC) substitution treatment is typically low threshold and therefore has the capacity to reach wider groups of opiate users. Decisions to prescribe DHC to patients with less severe opiate disorders centre on its perceived safety, reduced toxicity, shorter half-life and more rapid onset of action, and potential retention of patients. This review set out to investigate the effects of DHC in comparison to other pharmaceutical opioids and placebos in the detoxification and substitution of individuals with opiate use disorders.
OBJECTIVES
To investigate the effectiveness of DHC in reducing illicit opiate use and other health-related outcomes among adults compared to other drugs or placebos used for detoxification or substitution therapy.
SEARCH METHODS
In February 2019 we searched Cochrane Drugs and Alcohol's Specialised Register, CENTRAL, PubMed, Embase and Web of Science. We also searched for ongoing and unpublished studies via ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Trialsjournal.com. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.
SELECTION CRITERIA
We included randomised controlled trials that evaluated the effect of DHC for detoxification and maintenance substitution therapy for adolescent (aged 15 years and older) and adult illicit opiate users. The primary outcomes were abstinence from illicit opiate use following detoxification or maintenance therapy measured by self-report or urinalysis. The secondary outcomes were treatment retention and other health and behaviour outcomes.
DATA COLLECTION AND ANALYSIS
We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence.
MAIN RESULTS
We included three trials (in five articles) with 385 opiate-using participants that measured outcomes at different follow-up periods in this review. Two studies with 150 individuals compared DHC with buprenorphine for detoxification, and one study with 235 participants compared DHC to methadone for maintenance substitution therapy. We downgraded the quality of evidence mainly due to risk of bias and imprecision. For the two studies that compared DHC to buprenorphine, we found low-quality evidence of no significant difference between DHC and buprenorphine for detoxification at six-month follow-up (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.25 to 1.39; P = 0.23) in the meta-analysis for the primary outcome of abstinence from illicit opiates. Similarly, low-quality evidence indicated no difference for treatment retention (RR 1.29, 95% CI 0.99 to 1.68; P = 0.06). In the single trial that compared DHC to methadone for maintenance substitution therapy, the evidence was also of low quality, and there may be no difference in effects between DHC and methadone for reported abstinence from illicit opiates (mean difference (MD) -0.01, 95% CI -0.31 to 0.29). For treatment retention at six months' follow-up in this single trial, the RR calculated with an intention-to-treat analysis also indicated that there may be no difference between DHC and methadone (RR 1.04, 95% CI 0.94 to 1.16). The studies that compared DHC to buprenorphine reported no serious adverse events, while the DHC versus methadone study reported one death due to methadone overdose.
AUTHORS' CONCLUSIONS
We found low-quality evidence that DHC may be no more effective than other commonly used pharmacological interventions in reducing illicit opiate use. It is therefore premature to make any conclusive statements about the effectiveness of DHC, and it is suggested that further high-quality studies are conducted, especially in low- to middle-income countries.
Topics: Analgesics, Opioid; Codeine; Humans; Maintenance Chemotherapy; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic
PubMed: 32068247
DOI: 10.1002/14651858.CD012254.pub2 -
Reproductive Biomedicine Online Mar 2016The objectives of this study were to determine whether the main opioid receptor (OPRM1) is present on human granulosa cells and if exogenous opiates and their...
The objectives of this study were to determine whether the main opioid receptor (OPRM1) is present on human granulosa cells and if exogenous opiates and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production via OPRM1. Granulosa cells were isolated from women undergoing oocyte retrieval for IVF. Complementary to the primary cells, experiments were conducted using COV434, a well-characterized human granulosa cell line. Identification and localization of opiate receptor subtypes was carried out using Western blot and flow cytometry. The effect of opiate antagonist on granulosa cell VEGF secretion was assessed by enzyme-linked immunosorbent assay. For the first time, the presence of OPRM1 on human granulosa cells is reported. Blocking of opiate signalling using naloxone, a specific OPRM1 antagonist, significantly reduced granulosa cell-derived VEGF levels in both COV434 and granulosa-luteal cells (P < 0.01). The presence of opiate receptors and opiate signalling in granulosa cells suggest a possible role in VEGF production. Targeting this signalling pathway could prove promising as a new clinical option in the prevention and treatment of ovarian hyperstimulation syndrome.
Topics: Blotting, Western; Cell Line; Cellular Microenvironment; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Granulosa Cells; Humans; Naloxone; Opiate Alkaloids; Receptors, Opioid, mu; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 26803207
DOI: 10.1016/j.rbmo.2015.12.006