-
Annals of Palliative Medicine Mar 2020In this era of crisis and controversy surrounding opioid therapy, we must remember that cancer patients entrust us with supporting them through what might be the most... (Review)
Review
In this era of crisis and controversy surrounding opioid therapy, we must remember that cancer patients entrust us with supporting them through what might be the most difficult, and oftentimes final, period of their life. The factors that affect the benefits and risks of opioid use in cancer patients and the non-cancer population are quite different. In fact, opioid-associated deaths are 10 times less likely in the former than the latter population, suggesting that a reluctance to initiate opioids in cancer patients can risk under treatment of complex pain. In this review, we outline the considerations and evidence-based practices required to manage the clinical situations that challenge the judicious use of opioids in patients with cancer. A comprehensive review that enable us to better understand and quantify the root causes of variability in pain control, as well as risks of opioid misuse or abuse, would arm healthcare providers with the tools they need to implement multi-modal approaches to treatment planning.
Topics: Analgesics, Opioid; Cancer Pain; Disease Management; Humans; Opioid-Related Disorders; Pain Management; Pain Measurement
PubMed: 32233627
DOI: 10.21037/apm.2020.03.04 -
Molecular Pharmacology Oct 2020Millions of Americans suffer from opiate use disorder, and over 100 die every day from opioid overdoses. Opioid use often progresses into a vicious cycle of abuse and... (Review)
Review
Millions of Americans suffer from opiate use disorder, and over 100 die every day from opioid overdoses. Opioid use often progresses into a vicious cycle of abuse and withdrawal, resulting in very high rates of relapse. Although the physical and psychologic symptoms of opiate withdrawal are well-documented, sleep disturbances caused by chronic opioid exposure and withdrawal are less well-understood. These substances can significantly disrupt sleep acutely and in the long term. Yet poor sleep may influence opiate use, suggesting a bidirectional feed-forward interaction between poor sleep and opioid use. The neurobiology of how opioids affect sleep and how disrupted sleep affects opioid use is not well-understood. Here, we will summarize what is known about the effects of opioids on electroencephalographic sleep in humans and in animal models. We then discuss the neurobiology interface between reward-related brain regions that mediate arousal and wakefulness as well as the effect of opioids in sleep-related brain regions and neurotransmitter systems. Finally, we summarize what is known of the mechanisms underlying opioid exposure and sleep. A critical review of such studies, as well as recommendations of studies that evaluate the impact of manipulating sleep during withdrawal, will further our understanding of the cyclical feedback between sleep and opioid use. SIGNIFICANCE STATEMENT: We review recent studies on the mechanisms linking opioids and sleep. Opioids affect sleep, and sleep affects opioid use; however, the biology underlying this relationship is not understood. This review compiles recent studies in this area that fill this gap in knowledge.
Topics: Analgesics, Opioid; Animals; Brain; Electroencephalography; Humans; Opioid-Related Disorders; Sleep
PubMed: 32198209
DOI: 10.1124/mol.119.119107 -
Behavioural Pharmacology Apr 2020Although the gut and brain are separate organs, they communicate with each other via trillions of intestinal bacteria that collectively make up one's gut microbiome.... (Review)
Review
Although the gut and brain are separate organs, they communicate with each other via trillions of intestinal bacteria that collectively make up one's gut microbiome. Findings from both humans and animals support a critical role of gut microbes in regulating brain function, mood, and behavior. Gut bacteria influence neural circuits that are notably affected in addiction-related behaviors. These include circuits involved in stress, reward, and motivation, with substance use influencing gut microbial abnormalities, suggesting significant gut-brain interactions in drug addiction. Given the overwhelming rates of opioid overdose deaths driven by abuse and addiction, it is essential to characterize mechanisms mediating the abuse potential of opioids. We discuss in this review the role of gut microbiota in factors that influence opioid addiction, including incentive salience, reward, tolerance, withdrawal, stress, and compromised executive function. We present clinical and preclinical evidence supporting a bidirectional relationship between gut microbiota and opioid-related behaviors by highlighting the effects of opioid use on gut bacteria, and the effects of gut bacteria on behavioral responses to opioids. Further, we discuss possible mechanisms of this gut-brain communication influencing opioid use. By clarifying the relationship between the gut microbiome and opioid-related behaviors, we improve understanding on mechanisms mediating reward-, motivation-, and stress-related behaviors and disorders, which may contribute to the development of effective, targeted therapeutic interventions in opioid dependence and addiction.
Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Brain; Drug Tolerance; Gastrointestinal Microbiome; Humans; Motivation; Opioid-Related Disorders; Reward
PubMed: 31895059
DOI: 10.1097/FBP.0000000000000538 -
Genes Aug 2021Prescription opioids are used for some chronic pain conditions. However, generally, long-term therapy has unwanted side effects which may trigger addiction, overdose,... (Review)
Review
Prescription opioids are used for some chronic pain conditions. However, generally, long-term therapy has unwanted side effects which may trigger addiction, overdose, and eventually cause deaths. Opioid addiction and chronic pain conditions have both been associated with evidence of genetic and epigenetic alterations. Despite intense research interest, many questions about the contribution of epigenetic changes to this typology of addiction vulnerability and development remain unanswered. The aim of this review was to summarize the epigenetic modifications detected in specific tissues or brain areas and associated with opioid prescription and misuse in patients who have initiated prescribed opioid management for chronic non-cancer pain. The review considers the effects of opioid exposure on the epigenome in central and peripheral tissues in animal models and human subjects and highlights the mechanisms in which opioid epigenetics may be involved. This will improve our current understanding, provide the basis for targeted, personalized pain management, and thus balance opioid risks and benefits in managing chronic pain.
Topics: Analgesics, Opioid; Animals; Epigenesis, Genetic; Humans; Opioid-Related Disorders; Pain Management
PubMed: 34440400
DOI: 10.3390/genes12081226 -
Cold Spring Harbor Perspectives in... Feb 2021Opioid drugs are highly valued as potent analgesics; however, there are significant risks associated with long-term use because of their abuse liability. Opioids cause... (Review)
Review
Opioid drugs are highly valued as potent analgesics; however, there are significant risks associated with long-term use because of their abuse liability. Opioids cause changes in ventral tegmental area (VTA) gene expression and cell activity that have been linked to addiction-related behaviors in rodent models. Here, we focus on VTA dopamine (DA) neurons and review the cellular, structural, and synaptic plasticity changes induced by acute and chronic opioid exposure. We also discuss many avenues for future research including determination of whether opioid neuroadaptations are specific for subpopulations of VTA DA neurons. A better understanding of the molecular adaptations within the cells and circuits that drive opioid abuse is crucial for the development of better treatments for substance use disorders and to create novel, safer pain-relieving therapeutics.
Topics: Analgesics, Opioid; Animals; Dopaminergic Neurons; Humans; Neuronal Plasticity; Ventral Tegmental Area
PubMed: 31964652
DOI: 10.1101/cshperspect.a039362 -
Expert Opinion on Drug Metabolism &... Feb 2020: Opioids continue to be used widely for pain management. Widespread availability of prescription opioids has led to opioid abuse and addiction. Besides steps to reduce... (Review)
Review
: Opioids continue to be used widely for pain management. Widespread availability of prescription opioids has led to opioid abuse and addiction. Besides steps to reduce inappropriate prescribing, exploiting opioid pharmacology to make their use safer is important.: This article discusses the pathology and factors underlying opioid abuse. Pharmacokinetic and pharmacodynamic properties affecting abuse liability of commonly abused opioids have been highlighted. These properties inform the development of ideal abuse deterrent products. Mechanisms and cost-effectiveness of available abuse deterrent products have been reviewed in addition to the pharmacology of medications used to treat addiction.: The opioid crisis presents unique challenges to managing pain effectively given the limited repertoire of strong analgesics. The 5-point strategy to combat the opioid crisis calls for better preventive, treatment, and recovery services, better data, better pain management, better availability of overdose-reversing drugs and better research. There is an urgent need to decrease the cost of abuse deterrent opioids which deters their cost-effectiveness. In addition, discovery of novel analgesics, further insight into central and peripheral pain mechanisms, understanding genomic risk profiles for efficient targeted efforts, and education will be key to winning this fight against the opioid crisis.
Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Animals; Cost-Benefit Analysis; Drug Overdose; Humans; Inappropriate Prescribing; Opioid Epidemic; Opioid-Related Disorders; Pain
PubMed: 31976778
DOI: 10.1080/17425255.2020.1721458 -
British Journal of Pharmacology Apr 2023Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the... (Review)
Review
Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non-opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
Topics: Humans; Opioid-Related Disorders; Analgesics, Opioid; Methadone; Buprenorphine; Naltrexone
PubMed: 34128238
DOI: 10.1111/bph.15592 -
Current Neuropharmacology Apr 2017Chronic pain management represents a serious healthcare problem worldwide. Chronic pain affects approximately 20% of the adult European population and is more frequent... (Review)
Review
Chronic pain management represents a serious healthcare problem worldwide. Chronic pain affects approximately 20% of the adult European population and is more frequent in women and older people. Unfortunately, its management in the community remains generally unsatisfactory and rarely under the control of currently available analgesics. Opioids have been used as analgesics for a long history and are among the most used drugs; however, while there is no debate over their short term use for pain management, limited evidence supports their efficacy of long-term treatment for chronic non-cancer pain. Therapy with opioids is hampered by inter-individual variability and serious side effects and some opioids often result ineffective in the treatment of chronic pain and their use is controversial. Accordingly, for a better control of chronic pain a deeper knowledge of the molecular mechanisms underlying resistance to opiates is mandatory.
Topics: Analgesics, Opioid; Animals; Chronic Pain; Humans; Pain Management
PubMed: 28503117
DOI: 10.2174/1570159X14666161101092822 -
BMC Emergency Medicine Sep 2023Optimizing opioid prescriptions in the emergency department is essential to address the opioid pandemic while ensuring patient wellbeing. This requires a comprehensive...
Optimizing opioid prescriptions in the emergency department is essential to address the opioid pandemic while ensuring patient wellbeing. This requires a comprehensive approach that includes exploring alternatives to opioids for pain management, identifying individuals at risk for opioid addiction, implementing evidence-based guidelines, and involving doctors in the management of opioid addiction.
Topics: Humans; Analgesics, Opioid; Opioid-Related Disorders; Emergency Service, Hospital; Pain Management; Prescriptions
PubMed: 37726650
DOI: 10.1186/s12873-023-00880-0 -
American Journal of Surgery Oct 2020
Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Inappropriate Prescribing; Practice Patterns, Physicians'; Surgeons
PubMed: 32807384
DOI: 10.1016/j.amjsurg.2020.07.021