Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on Chronic Opioid Therapy.
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ABSTRACT:
SUBMITTER: Chu LF
PROVIDER: S-EPMC5610060 | biostudies-literature | 2017 Sep/Oct
REPOSITORIES: biostudies-literature
Publications
Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on Chronic Opioid Therapy.
Chu Larry F LF Sun John J Clemenson Anna A Erlendson Matthew J MJ Rico Tom T Cornell Erika E Obasi Hannah H Sayyid Zahra N ZN Encisco Ellen M EM Yu Jeff J Gamble Jamison G JG Carroll Ian I Clark J David JD
Journal of addiction medicine 20170901 5
<h4>Objectives</h4>Individuals taking opioids for an extended period of time may become physically dependent, and will therefore experience opioid withdrawal should they stop taking the medication. Previous work in animal and human models has shown that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In this study, we investigated if ondansetron, a 5-HT3-receptor antagonist, could reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans.<h4>Methods< ...[more]
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Project description:Introduction:Chronic lower back pain is a leading cause of disability in US adults. Opioid use continues to be controversial despite the Centers for Disease Control and Prevention guidance on chronic pain management to use nonpharmacologic and nonopioid pharmacologic interventions. The objectives of the study were to assess the impact of early physical therapy (PT) intervention on improving functionality and reducing opioid burden in patients with chronic lower back pain. Methods:A single-center, retrospective chart review of patients receiving ?6 PT visits and treated with either opioids first (OF) or PT first (PTF) therapy for chronic lower back pain were evaluated. Concomitant use of nonopioid and nonpharmacologic therapy was permitted. The Oswestry Disability Index (ODI), a survey measuring functionality, was recorded for PTF group. Pain scores and medication use including opioids were collected at treatment initiation and completion. Results:One hundred and eighty patients were included in three groups: OF group (n?=?60), PTF group (n?=?60), and PTF?+?ODI group (n?=?60). The PTF?+?ODI group had mean ODI reduction of 11.9% (P?<?.001). More OF patients were lost to follow up (68.3%) or failed PT (60%) compared to the PTF group, 38.3% and 3.3% (P?<?.001). Reduction in both opioid and nonopioid medications as well as pain scores were observed but not statistically significant. Discussion:Early PT resulted in improved functionality, decreased pain, and reduced medication use upon PT completion. These findings suggest PT, along with nonopioid modalities, are a viable first-line option for the management of chronic lower back pain.
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Project description:The development of substance use disorder (SUD) is a complex process involving multiple neurocircuitries and brain regions. The amygdala is a region that mediates the withdrawal effect as well as anxiety and depression-like behaviors. However, the transcriptional changes in each cell type during SUD is largely unknown. Here we performed single-cell RNA sequencing and classified all cell types in the mouse amygdala under opioid dependence and withdrawal states. Our data revealed distinct changes in key biological processes, such as immune response, inflammation, synaptic transmission, and mitochondrial respiration in different cell populations. Dramatic differences were unraveled in the transcriptional profiles between dependence and withdrawal states. This report is the first single-cell RNA sequencing dataset from the amygdala under opioid dependence and withdrawal conditions, providing unique insights in understanding brain alterations during SUD, especially at the molecular and cellular levels.
2023-11-08 | GSE207128 | GEO
Project description:BACKGROUND: The incidence of neonatal opioid withdrawal is increasing in both Canada and the United States. However, the degree to which the treatment of pain with opioids, rather than the misuse of prescription opioids or heroin, contributes to the prevalence of neonatal opioid withdrawal remains unknown. METHODS: We conducted a retrospective, population-based, cross-sectional study between 1992 and 2011 in Ontario with 2 objectives. First, we determined the annual incidence of neonatal abstinence syndrome. Second, using data from a subset of women eligible for publicly funded prescription drugs, we determined what proportion of women who deliver an infant with neonatal abstinence syndrome were given a prescription for an opioid before and during pregnancy. RESULTS: The incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births in 2011. During the final 5 years of the study, we identified 927 deliveries of infants with neonatal abstinence syndrome to mothers who were public drug plan beneficiaries. Of these mothers, 67% had received an opioid prescription in the 100 days preceding delivery, including 53.3% who received methadone, an increase from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001). Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001). INTERPRETATION: The incidence of neonatal opioid withdrawal in Ontario has increased substantially over the last 20 years. Most of the women in this cohort who delivered an infant with neonatal abstinence syndrome had received a prescription for an opioid both before and during their pregnancy.
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Project description:The long-term effects of opioids on sensitization processes are believed to be mediated through the N-methyl-D-aspartate receptor. Quantitative sensory testing (QST) changes observed after a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed after a .05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naive or were chronically using opioids for chronic noncancer pain are presented. No baseline QST differences were noted between the 4 groups at baseline. Comparison of changes preinfusion with postinfusion QST measurements resulted in decreased average change in temporal summation response between opioid subjects who received a placebo compared with those who received a ketamine infusion (-5.22, SD = 9.96 vs 13.81, SD = 19.55; P = .004). Additionally, the average change in temporal summation was decreased among subjects who received a ketamine infusion and were not chronically using opioids compared with subjects who were using chronic opioids and received a placebo infusion (-1.91, SD = 13.25 vs 13.81, SD = 19.55; P = .007). The results indicate that low-dose ketamine infusions produce subtle changes in QST phenotypes that are modified by the chronic use of opioids. This illustrates the potential diagnostic and therapeutic value of ketamine in the setting of chronic opioid use. PERSPECTIVE:The presented data further our understanding of modulation of sensory perception in the setting of chronic opioid use and the role of the N-methyl-D-aspartate receptor. The use of low-dose ketamine infusions may be useful for the treatment as well as diagnosis of opioid-related neuropathic conditions.
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Project description:This study examined the role of spinal calcitonin gene-related peptide (CGRP), substance P, and prostaglandins in the development and expression of opioid physical dependence. Administration of escalating doses (5 - 100 mg kg-1, i.p.) of morphine for 7 days markedly elevated CGRP and substance P- immunoreactivity in the dorsal horn of the rat spinal cord. Naloxone (2 mg kg-1, i.p.) challenge decreased both CGRP and substance P immunoreactivity and precipitated a robust withdrawal syndrome. Acute intrathecal pre-treatment with a CGRP receptor antagonist, CGRP(8 - 37) (4, 8 microg), a substance P receptor antagonist, SR 140333 (1.4, 2.8 microg), a cyclo-oxygenase (COX) inhibitor, ketorolac (30, 45 microg), and COX-2 selective inhibitors, DuP 697 (10, 30 microg) and nimesulide (30 microg), 30 min before naloxone challenge, partially attenuated the symptoms of morphine withdrawal. CGRP(8 - 37) (8 microg), but no other agents, inhibited the decrease in CGRP immunoreactivity. Chronic intrathecal treatment with CGRP(8 - 37) (4, 8 microg), SR 140333 (1.4 microg), ketorolac (15, 30 microg), DuP 697 (10, 30micro g), and nimesulide (30 microg), delivered with daily morphine injection significantly attenuated both the symptoms of withdrawal and the decrease in CGRP but not substance P immunoreactivity. The results of this study suggest that activation of CGRP and substance P receptors, at the spinal level, contributes to the induction and expression of opioid physical dependence and that this activity may be partially expressed through the intermediary actions of prostaglandins.
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Project description:ImportanceNonpharmacologic methods of reducing the risk of new chronic opioid use among patients with musculoskeletal pain are important given the burden of the opioid epidemic in the United States.ObjectiveTo determine the association between early physical therapy and subsequent opioid use in patients with new musculoskeletal pain diagnosis.Design, setting, and participantsThis cross-sectional analysis of health care insurance claims data between January 1, 2007, and December 31, 2015, included privately insured patients who presented with musculoskeletal pain to an outpatient physician office or an emergency department at various US facilities from January 1, 2008, to December 31, 2014. The sample comprised 88 985 opioid-naive patients aged 18 to 64 years with a new diagnosis of musculoskeletal shoulder, neck, knee, or low back pain. The data set (obtained from the IBM MarketScan Commercial database) included person-level International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis codes, Current Procedural Terminology codes, and date of service as well as pharmaceutical information (National Drug Code, generic name, dose, and number of days supplied). Early physical therapy was defined as at least 1 session received within 90 days of the index date, the earliest date a relevant diagnosis was provided. Data analysis was conducted from March 1, 2018, to May 18, 2018.Main outcomes and measuresOpioid use between 91 and 365 days after the index date.ResultsOf the 88 985 patients included, 51 351 (57.7%) were male and 37 634 (42.3%) were female with a mean (SD) age of 46 (11.0) years. Among these patients, 26 096 (29.3%) received early physical therapy. After adjusting for potential confounders, early physical therapy was associated with a statistically significant reduction in the incidence of any opioid use between 91 and 365 days after the index date for patients with shoulder pain (odds ratio [OR], 0.85; 95% CI, 0.77-0.95; P = .003), neck pain (OR, 0.92; 95% CI, 0.85-0.99; P = .03), knee pain (OR, 0.84; 95% CI, 0.77-0.91; P < .001), and low back pain (OR, 0.93; 95% CI, 0.88-0.98; P = .004). For patients who did use opioids, early physical therapy was associated with an approximately 10% statistically significant reduction in the amount of opioid use, measured in oral morphine milligram equivalents, for shoulder pain (-9.7%; 95% CI, -18.5% to -0.8%; P = .03), knee pain (-10.3%; 95% CI, -17.8% to -2.7%; P = .007), and low back pain (-5.1%; 95% CI, -10.2% to 0.0%; P = .046), but not for neck pain (-3.8%; 95% CI, -10.8% to 3.3%; P = .30).Conclusions and relevanceEarly physical therapy appears to be associated with subsequent reductions in longer-term opioid use and lower-intensity opioid use for all of the musculoskeletal pain regions examined.
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Project description:BACKGROUND:Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. METHODS:Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. RESULTS:Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. CONCLUSIONS:These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety/compulsive-like behaviors may be driven by greater kappa opioid receptor sensitivity and a hypodopaminergic state of the nucleus accumbens.
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Project description:Prescription opioid misuse is a significant public health problem as well as a patient safety concern. Primary care providers (PCPs) are the leading prescribers of opioids for chronic pain, yet few PCPs follow standard practice guidelines regarding assessment and monitoring. This cluster randomized controlled trial will determine whether four implementation strategies; nurse care management, use of a patient registry, academic detailing, and electronic tools, will increase PCP adherence to chronic opioid therapy guidelines and reduce opioid misuse among patients, relative to electronic tools alone. The implementation strategies and intervention content are based on the chronic care model.We include 53 PCPs from three Boston-area community health centers and one urban safety-net hospital-based primary care practice who have at least four patients meeting the following inclusion criteria: 1) age?18; 2) one or more completed visits to the primary care practice in the past year; 3) long-term opioid treatment defined as three or more opioid prescriptions written at least 21days apart within 6months and 4) an inpatient or outpatient ICD-9-CM diagnosis for musculoskeletal or neuropathic pain. We consider PCPs to be study subjects, and obtained a waiver of informed consent for patients because the study is promoting an established standard of care. We enrolled participants (PCPs) from December 2012 through March 2015. PCPs were randomized to receive the intervention, which includes four components: 1) nurse care management, 2) use of a patient registry, 3) academic detailing, and 4) electronic tools, or a control condition, which includes only the use of the electronic tools. The intervention PCPs receive the services of a nurse-managed registry for planning individual patient care and conducting population-based care for patients receiving opioids for chronic pain. In academic detailing visits, trained co-investigators provide intervention PCPs with individualized education to change prescribing practice. Electronic tools, located on a web site external to the EMR, www.mytopcare.org, include validated instruments to assess patient status, and management resources to facilitate PCP adherence to suggested monitoring. Electronic tools are available to PCPs in both study arms. The primary outcomes are PCP adherence to chronic opioid therapy guidelines and patient opioid misuse. Secondary outcomes include measures of substance abuse, possible opioid diversion, and level of opioid risk among patients. We will follow PCPs and their estimated 1200 chronic pain patients for 1year after study enrollment. To determine whether the intervention condition achieves greater adherence to guidelines and reduced opioid misuse after 1year compared to the control condition, we will compare the baseline and follow-up measures of the individual patients, stratifying by intervention status and noting differences that are statistically significant at the p=0.05 level. Analyses will be based on intent-to-treat.Randomization resulted in groups with similar baseline characteristics. The ages of PCPs are evenly distributed, with inclusion of both PCPs who have recently completed training and those who have been in practice for more than 20years. Two-thirds of enrolled PCPs are women, and one-third are non-white.The study will determine the impact of this multicomponent intervention on improving PCP adherence to guidelines and reducing opioid misuse among patients.
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