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The European Journal of Neuroscience Jul 2020Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one... (Review)
Review
The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal.
Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one hand, the dopaminergic mesocorticolimbic system evaluates the rewarding or reinforcing potential of a stimulus, while on the other, the noradrenergic stress response system evaluates the risk of threat, commanding attention, and engaging emotional and physical behavioral responses. Sex-specific patterns in the anatomy and function of the arousal system suggest that sexually divergent therapeutic approaches may be advantageous for neurological disorders involving arousal, learning, and memory. From the lens of the triple network model of psychopathology, we argue that post-traumatic stress disorder and opiate substance use disorder arise from maladaptive learning responses that are perpetuated by hyperarousal of the salience network. We present evidence that catecholamine-modulated learning and stress-responsive circuitry exerts substantial influence over the salience network and its dysfunction in stress-related psychiatric disorders, and between the sexes. We discuss the therapeutic potential of targeting the endogenous cannabinoid system; a ubiquitous neuromodulator that influences learning, memory, and responsivity to stress by influencing catecholamine, excitatory, and inhibitory synaptic transmission. Relevant preclinical data in male and female rodents are integrated with clinical data in men and women in an effort to understand how ideal treatment modalities between the sexes may be different.
Topics: Catecholamines; Female; Humans; Male; Memory; Norepinephrine; Opiate Alkaloids; Stress Disorders, Post-Traumatic
PubMed: 32125035
DOI: 10.1111/ejn.14714 -
The Journal of Trauma and Acute Care... Dec 2023Rib fractures are common injuries which can be associated with acute pain and chronic disability. While most rib fractures ultimately go on to achieve bony union, a...
Chest Wall Injury Society recommendation for surgical stabilization of nonunited rib fractures to decrease pain, reduce opiate use, and improve patient reported outcomes in patients with rib fracture nonunion after trauma.
BACKGROUND
Rib fractures are common injuries which can be associated with acute pain and chronic disability. While most rib fractures ultimately go on to achieve bony union, a subset of patients may go on to develop non-union. Management of these nonunited rib fractures can be challenging and variability in management exists.
METHODS
The Chest Wall Injury Society's Publication Committee convened to develop recommendations for use of surgical stabilization of nonunited rib fractures (SSNURF) to treat traumatic rib fracture nonunions. PubMed, Embase, and the Cochrane database were searched for pertinent studies. Using a process of iterative consensus, all committee members voted to accept or reject the recommendation.
RESULTS
No identified studies compared SSNURF to alternative therapy and the overall quality of the body of evidence was rated as low. Risk of bias was identified in all studies. Despite these limitations, there is lower-quality evidence suggesting that SSNURF may be beneficial for decreasing pain, reducing opiate use, and improving patient reported outcomes among patients with symptomatic rib nonunion. However, these benefits should be balanced against risk of symptomatic hardware failure and infection.
CONCLUSION
This guideline document summarizes the current CWIS recommendations regarding use of SSNURF for management of rib nonunion.
LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Topics: Humans; Rib Fractures; Opiate Alkaloids; Thoracic Wall; Thoracic Injuries; Ribs; Fractures, Ununited; Acute Pain
PubMed: 37728432
DOI: 10.1097/TA.0000000000004083 -
JAMA Network Open Jun 2018
Topics: Analgesics, Opioid; Humans; Molecular Weight; Opiate Alkaloids; Opioid-Related Disorders; Politics
PubMed: 30646076
DOI: 10.1001/jamanetworkopen.2018.0451 -
Frontiers in Public Health 2022Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding...
BACKGROUND
Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding the transmission of infectious diseases either sexually or by intravenous drug abuse.
OBJECTIVE
The aim of this study was to analyze the association between hepatitis C virus (HCV) infection and personality dysfunction in opiate addicts on opioid substitution treatment.
METHODS
This was a cross-sectional, observational investigation of patients over 18 years of age who were actively participating in opioid substitution treatment at five centers in Bosnia and Herzegovina. The occurrence of HCV infection was the primary study outcome, and personality functioning, the main independent variable, was assessed using the Severity Indices of Personality Problems (SIPP-118) questionnaire. The association between scores of personality functioning domains items and HCV infection status was determined by binary logistic regression analysis.
RESULTS
Patients on opioid substitution therapy with HCV infection more frequently had personality disorders (OR 2.168, 95% CI 1.161-4.05) and were treated longer than patients without HCV infection (OR 1.076, 95% CI 1.015-1.14). HCV infection was associated with lower self-respect (OR 0.946, 95% CI 0.906-0.988), decreased capacity to have enduring relationships with other people (OR 0.878, 95% CI 0.797-0.966), and lower capability to cooperate with others (OR 0.933, 95%CI 0.888-0.98). On the other hand, except for self-respect, other elements of the Identity Integration domain (enjoyment, purposefulness, stable self-image, and self-reflexive functioning), when more functional, increased the risk of HCV infection.
CONCLUSIONS
Our study demonstrates that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if their personality is dysfunctional, especially in the aspects of self-respect, enduring relationships, and cooperativity. The risk is even higher in addicts who have an established diagnosis of any kind of personality disorder.
Topics: Adolescent; Adult; Cross-Sectional Studies; Hepacivirus; Hepatitis C; Humans; Opiate Alkaloids; Opiate Substitution Treatment; Opioid-Related Disorders; Personality; Personality Disorders
PubMed: 36159261
DOI: 10.3389/fpubh.2022.1009413 -
Medical Science Monitor : International... Jun 2004The demonstration of the multiplicity of opiate receptor types has led to the understanding that, depending on their site of action, opioid peptides as well as opiate...
The demonstration of the multiplicity of opiate receptor types has led to the understanding that, depending on their site of action, opioid peptides as well as opiate alkaloids may bind to more than one opiate receptor subtype. In addition to the two main mu opiate receptor subtypes, mu1 and mu2, our laboratory has demonstrated a third mu opiate receptor (mu3) that is selective for opiate alkaloids but insensitive to opioid peptides. Recently, the mu3 opiate receptor subtype has been cloned from human immune, vascular and neural tissues. This mu3 story complements many biochemical reports; demonstrating morphine is an endogenous signaling molecule, functioning in the capacity of a neurotransmitter and hormone. Adding additional evidence to this hypothesis are the findings of morphine precursors in mammalian and invertebrate tissues. The reports published in this issue of MSM complement this story while advancing the hypothesis by placing opiate alkaloid signaling in limbic structures. The pharmacological characteristics of exogenous morphine find a role for explaining morphine action in an "emotional" and belief setting.
Topics: Brain; Health; Humans; Medicine; Morphine; Receptors, Opioid
PubMed: 15173675
DOI: No ID Found -
Psychopharmacology Jan 2022The treatment of opiate addiction is an unmet medical need. Repeated exposure to opiates disrupts cognitive performance. Opioid substitution therapy, with, e.g.,...
RATIONALE
The treatment of opiate addiction is an unmet medical need. Repeated exposure to opiates disrupts cognitive performance. Opioid substitution therapy, with, e.g., methadone, may further exacerbate the cognitive deficits. Growing evidence suggests that mitragynine, the primary alkaloid from the Kratom (Mitragyna speciosa) leaves, may serve as a promising alternative therapy for opiate addiction. However, the knowledge of its health consequences is still limited.
OBJECTIVES
We aimed to examine the cognitive effects of mitragynine substitution in morphine-withdrawn rats. Furthermore, we asked whether neuronal addiction markers like the brain-derived neurotrophic factor (BDNF) and Ca/calmodulin-dependent kinase II alpha (αCaMKII) might mediate the observed effects.
METHODS
Male Sprague-Dawley rats were given morphine at escalating doses before treatment was discontinued to induce a spontaneous morphine withdrawal. Then, vehicle or mitragynine (5 mg/kg, 15 mg/kg, or 30 mg/kg) substitution was given for 3 days. A vehicle-treated group was used as a control. Withdrawal signs were scored after 24 h, 48 h, and 72 h, while novel object recognition (NOR) and attentional set-shifting (ASST) were tested during the substitution period.
RESULTS
Discontinuation of morphine significantly induced morphine withdrawal signs and cognitive deficit in the ASST. The substitution with mitragynine was able to alleviate the withdrawal signs. Mitragynine did not affect the recognition memory in the NOR but significantly improved the reversal learning deficit in the morphine-withdrawn rats.
CONCLUSIONS
These data support the idea that mitragynine could be used as safe medication therapy to treat opiate addiction with beneficial effects on cognitive deficits.
Topics: Animals; Cognition; Male; Mitragyna; Morphine; Rats; Rats, Sprague-Dawley; Secologanin Tryptamine Alkaloids
PubMed: 34693456
DOI: 10.1007/s00213-021-05996-4 -
Canadian Journal of Surgery. Journal... 2023Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres...
BACKGROUND
Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia).
METHODS
We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon's preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72-96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects.
RESULTS
Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112-228 v. 242.4 mg, IQR 166.8-352) with and without RSC, respectively ( = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications.
CONCLUSION
The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings.
Topics: Humans; Opiate Alkaloids; Analgesics, Opioid; Retrospective Studies; Pain, Postoperative; Cohort Studies; Pancreaticoduodenectomy; Treatment Outcome; Analgesics; Morphine; Postoperative Complications; Catheters
PubMed: 37442583
DOI: 10.1503/cjs.006922 -
Clinical and Translational Science Feb 2023Administration of a widely used 5-hydroxytryptamine receptor (5HT R) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid...
Administration of a widely used 5-hydroxytryptamine receptor (5HT R) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid dependence and withdrawal responses in mice and humans. However, in several studies examining withdrawal symptoms in subjects with chronic opioid use disorders (OUDs), ondansetron exhibited reduced or absent efficacy. Because attenuation of opioid withdrawal symptomatology is mediated within the brain, this study examined single-dose ondansetron pharmacokinetics in the blood and brain of mice. We demonstrate that ondansetron concentrations in the brain (C ng/mg) are 1000-fold lower than the blood concentrations (C ng/ml) and decrease rapidly after ondansetron administration; and that a large percentage of brain ondansetron remains in the ventricular fluid. These results indicate that the ondansetron dose, and the time window between ondansetron and opioid administration, and when withdrawal is assessed are critical considerations for clinical studies involving subjects with chronic OUD. The pharmacokinetic results and the dosing considerations discussed here can be used to improve the design of subsequent clinical trials, which will test whether a more prolonged period of ondansetron administration can provide a desperately needed therapy that can prevent the development of neonatal opioid withdrawal syndrome in babies born to mothers with chronic OUD.
Topics: Humans; Mice; Animals; Ondansetron; Analgesics, Opioid; Opiate Alkaloids; Brain; Morphine; Opioid-Related Disorders; Substance Withdrawal Syndrome
PubMed: 36305236
DOI: 10.1111/cts.13440 -
Adicciones Jul 2021The use of opiate analgesics has led to a health and social emergency in the United States. In Spain, according to official data, the prescription of these drugs has...
The use of opiate analgesics has led to a health and social emergency in the United States. In Spain, according to official data, the prescription of these drugs has risen dramatically in the last decade. This study explores the prevalence of the use of these drugs and the health and socio-demographic characteristics of their consumers in the city of Madrid. A telephone survey was carried on a stratified, randomised sample, asking about the use of these drugs and whether or not they were medically prescribed. The sample consisted of n=8,845 subjects aged between 15 and 98 years. Sixteen percent stated that they had used these drugs in the last year and 9.1% had taken them in the last two weeks. Consumption was more frequent among women, lower social class and lower level of education. Among the youngest group (15-29 years old) 12.5% had already used it. Those who use opioids report worse perceived health, lower quality of life, more mental health problems, more loneliness, more use of other psychoactive drugs, more frequent daily use of tobacco and less problematic consumption of alcohol. Ten percent of those who use them do so without a doctor's prescription. Combining these data with the prescription data offered by the Ministry of Health, it is necessary to pay attention to a problem that may become apparent in the coming years, and the adoption of urgent measures to tackle it before it brings the Spanish situation closer to that already well known in countries of our socio-political environment is advised.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Female; Humans; Middle Aged; Opiate Alkaloids; Pharmaceutical Preparations; Quality of Life; Substance-Related Disorders; United States; Young Adult
PubMed: 32100043
DOI: 10.20882/adicciones.1335 -
ACS Chemical Neuroscience Oct 2018Opium is the latex from the opium poppy Papaver somniferum L., which humankind has utilized since ancient Mesopotamia all the way to modern times. Opium used to be... (Review)
Review
Opium is the latex from the opium poppy Papaver somniferum L., which humankind has utilized since ancient Mesopotamia all the way to modern times. Opium used to be surrounded in divine mystery or magic-like abilities and was given to cure a wide variety of diseases until its analgesic, antitussive, and antidiarrheal properties were understood, the resulting alkaloids were isolated, and their structure and properties unmasked. Opium went from being sold in any store front in the form of pills or tinctures with no prescription necessary for purchase or smoked in an opium den down the street, to then bringing about consumer advocacy and the right to know what is in a medication. Legislation was created to limit the prescribing and selling of medications to doctors and pharmacists as well as outlawing opium dens and smoking opium. This review focuses primarily on the uses of opium throughout history, the isolation of the principle alkaloids, and their structure elucidation.
Topics: History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Narcotics; Opiate Alkaloids; Opioid-Related Disorders; Opium; Papaver; United States
PubMed: 30247870
DOI: 10.1021/acschemneuro.8b00459