Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor ...Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.展开更多
The US opioid crisis has become a serious public health issue,causing tens of thousands of deaths and tremendous economic loss annually.Acupuncture,as a traditional non-pharmacological method of analgesia,has demonstr...The US opioid crisis has become a serious public health issue,causing tens of thousands of deaths and tremendous economic loss annually.Acupuncture,as a traditional non-pharmacological method of analgesia,has demonstrated extraor-dinary value in addressing this crisis.This paper systematically elucidates the causes and impacts of the US opioid crisis and deeply explores the neurobiological mechanisms of acupuncture analgesia,including the activation of the endogenous opioid system,neurotransmitter regulation,and anti-inflammatory and immune modulation via multiple pathways.By analyzing the clinical evidence for acupuncture in the management of acute and chronic pain,opioid dosage reduction,and addiction treatment,we demonstrate the feasibility and effi cacy of acupuncture as an alternative to opioid therapy.Research shows that acupuncture can not only eff ectively relieve various types of pain but also reduce opioid consumption and treat opioid dependence and addiction.However,the promotion of acupuncture in the US still faces multi-faceted challenges,including issues of standardization,limited insurance coverage,and insuffi cient high-quality evidence.Future eff orts should focus on strengthening multidisciplinary research collaboration,improving standardized treatment protocols,and integrating acupunc-ture into comprehensive pain management systems to provide a safer,more cost-eff ective,non-pharmacological alternative for resolving the opioid crisis.展开更多
BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question...BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question is“How does the use of opioid medications in pain management,compared with non-opioid medications,affect pain intensity over the short,intermediate,and long-term in adults with acute traumatic pain?”.METHODS The protocol was prospectively registered on the International Prospective Re-gister of Systematic Reviews:CRD42021279639.Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full,with the PICO framework:P:Adult patients with traumatic injuries,I:Opioid medications,C:Non-opioid medi-cations,O:A minimum clinically important difference(MCID)in pain.RESULTS After full-text screening,we included 14 studies in the qualitative synthesis.Of these 14 studies,12 were rando-mized clinical trials(RCTs)and 2 were pseudo-RCTs with a total of 2347 patients enrolled.There was heteroge-neity in both medication utilized and outcome in these studies;only two studies were homogeneous regarding the type of study conducted,the opioid used,its comparator,and the outcome explored.The MCID was evaluated in 8 studies,while in 6 studies,any measured pain reduction was considered as an outcome.In 11 cases,the setting of care was the Emergency Department;in 2 cases,care occurred out-of-hospital;and in one case,the setting was not well-specified.The included studies were found to have a low-moderate risk of bias.CONCLUSION Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury.Intravenous ketamine may cause more adverse events than other routes of administration.展开更多
Gastrointestinal endoscopy is a common examination for digestive system.The stimulation of endoscope often causes cough,nausea and vomiting,increased heart rate and blood pressure,arrhythmia,and even cardiovascular an...Gastrointestinal endoscopy is a common examination for digestive system.The stimulation of endoscope often causes cough,nausea and vomiting,increased heart rate and blood pressure,arrhythmia,and even cardiovascular and cerebrovascular accidents,thus makes people fear of this procedure.Sedation or anesthesia can effectively improve the safety,comfort and quality of gastrointestinal endoscopy.A small dose of opioids is a good adjuvant to sedatives.In this narrative review,we summarized the main roles of opioid analgesics in gastrointestinal endoscopy,including reducing visceral pain,throat irritation and the dose of sedatives.Moreover,the frequently used and novel opioids are reviewed.Classic fentanyl,sufentanil and dezocine are preferable by anesthesiologists.Newly approved oliceridine is promising to render ideal analgesic effects for gastrointestinal endoscopy.Clinical studies on oliceridine in endoscopic procedures are urgently needed.展开更多
Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic...Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic basis for variable itch incidence remains unknown.This study examined 3616 patients receiving epidural opioids,revealing an itch occurrence of 26.55%,with variations among opioid types and gender.Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms,notably rs1799971(A118G),that correlated with opioid-induced itch.Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch,mirroring human findings.The 118G allele demonstrated an anti-itch effect without impacting analgesia,addiction,or tolerance,offering insights for risk stratification and potential anti-itch pretreatment strategies.展开更多
BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vom...BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.展开更多
Objectives Retinal ischemia-reperfusion(RIR)injury results in irreversible visual impairments.The disruption of the outer blood-retinal barrier(OBRB)is a major ocular pathogenic process that RIR injury affects.Current...Objectives Retinal ischemia-reperfusion(RIR)injury results in irreversible visual impairments.The disruption of the outer blood-retinal barrier(OBRB)is a major ocular pathogenic process that RIR injury affects.Current clinical strategies are limited.This study aimed to elucidate how electroacupuncture(EA)protects the OBRB against RIR injury.Methods Male Wistar rats(7 weeks old,250 g to 280 g)were used in this study.Three independent experiments were conducted.First,Opioid peptide levels were quantified using enzyme-linked immunosorbent assay(ELISA).42 rats were randomly divided into 7 groups(n=6/group):Control:No treatment;high intraocular pressure(HIOP):Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming(Extra acupoint)and Jingming(BL1)for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;HIOP+100 Hz:RIR injury+100 Hz EA at Xinming and BL1 for 30 min;HIOP+2/100 Hz EA:RIR injury+2/100 Hz EA at Xinming and BL1 for 30 min;HIOP+4/20 Hz EA:RIR injury+4/20 Hz EA at Xinming and BL1 for 30 min.Second,retinal morphology was assessed by hematoxylin and eosin(HE)staining.20 rats were randomly allocated into 4 groups(n=5/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min.Third,the permeability of OBRB was evaluated using the fluorescein isothiocyanate(FITC)-dextran leakage assay.15 rats were randomly divided into 5 groups(n=3/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;Nal+HIOP+2 Hz EA:Intravitreal injection ofδ-opioid receptor antagonist Naltridole(10µl,100 nM)30 min before RIR injury induction,followed by 2 Hz EA treatment at Xinming and BL1 for 30 min.In vitro studies examined enkephalins'effects on oxygen–glucose deprivation/reperfusion(OGD/R)induced injury in ARPE‐19 cells.Cell viability was evaluated by cell counting kit-8(CCK-8)assay,and morphological changes were recorded by Molecular Devices.Apoptosis was detected by Annexin V-FITC flow cytometry.Delta opioid receptor(DOR)expression in total protein and membrane protein were analyzed by western blotting(WB).Immunofluorescence(IF)staining and WB assessed ZO-1 and Claudin-19.For cell-based assays,n indicates the number of biologically independent replicates.Results It was found that 2 Hz EA treatment increased enkephalins(methionine-enkephalin and leucine-enkephalin)levels(P<0.01),restoring the increased retinal thickness(P<0.05)and mitigating RGCs loss(P<0.05)post-RIR injury.FITC-dextran leakage in the outer retina was ameliorated by 2 Hz EA(P<0.05),reversibly countered by Naltrindole(P<0.05),a DOR antagonist.Treatment with 30µM enkephalins enhanced ARPE-19 cell viability(P<0.001,P<0.0001)and inhibited apoptosis(P<0.0001).Enkephalins elevated DOR levels in total protein(P<0.05)and membrane protein fractions(P<0.001,P<0.0001),as well as elevated ZO-1(P<0.001,P<0.01)and Claudin-19(P<0.0001,P<0.001)levels following OGD/R,counteracted by Naltrindole.Conclusion It was found that 2 Hz EA inhibits the breakdown of OBRB via enkephalins activate DOR in RIR injury.展开更多
In this article,we evaluate the findings of the study by Qian et al,which explores the efficacy of combining hyperthermia with opioid therapy for enhanced cancer pain management in patients with middle and late-stage ...In this article,we evaluate the findings of the study by Qian et al,which explores the efficacy of combining hyperthermia with opioid therapy for enhanced cancer pain management in patients with middle and late-stage gastrointestinal tumors.The study undertakes a retrospective analysis comparing traditional opioid therapy to an integrated approach of hyperthermia and opioids across 70 patients,highlighting significant benefits in pain control,reduction of opioid dosage,and minimization of adverse reactions.In our article,we not only discuss these fin-dings but also emphasize the broader implications for clinical practice,parti-cularly in enhancing patient outcomes through innovative pain management strategies.We advocate for further research to establish more robust data su-pporting this approach and to explore the mechanistic insights that enable these benefits.This discussion reflects on the potential paradigm shift in managing debilitating cancer-related pain,urging a reevaluation of current practices to incorporate these findings effectively.展开更多
1.The development history of enhanced recovery after surgery(ERAS)Enhanced recovery after surgery(ERAS)is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception.In 1997,P...1.The development history of enhanced recovery after surgery(ERAS)Enhanced recovery after surgery(ERAS)is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception.In 1997,Professor Henrik Kehlet,also known as the“father of ERAS”,from the University of Copenhagen in Denmark first proposed the ERAS concept and discovered its clinical feasibility and superiority,achieving remarkable results.ERAS was initially applied in colorectal surgery;subsequently,the concept gradually gained popularity and application worldwide.展开更多
Patients with chronic pancreatitis often experience severe,unrelenting abdominal pain,which can significantly impact their quality of life.Pain control,therefore,remains central to the overall management of chronic pa...Patients with chronic pancreatitis often experience severe,unrelenting abdominal pain,which can significantly impact their quality of life.Pain control,therefore,remains central to the overall management of chronic pancreatitis.Most of the strategies aimed at treating the pain of chronic pancreatitis are based on expert opinion and vary from one institution to another,as there are no uniform guidelines to direct a stepwise approach towards achieving this goal.In this editorial,we comment on best practice strategies targeted towards pain control in chronic pancreatitis,specifically highlighting the use of opioid medications in this patient population.We discuss various safe and efficacious prescription monitoring practices in this article.展开更多
BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a s...BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with PTSD than those without this disorder.AIM To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and Outcomes(PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical analysis.RESULTS A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and neck pain(28.7%;range: 3.6%-63%). In total,42.4% of the participants across studies had a diagnosis of PTSD(range: 4.7%-95%). In relation to opioid intake, we identified 2 different outcomes: opioid prescription and OUD. All the studies reported evidence of a greater prevalence of PTSD in CNCP patients who were receiving prescribed opioids and that PTSD was associated with OUD in CNCP patients.CONCLUSION Opioid analgesic prescription as the treatment of choice for CNCP patients should include screening for baseline PTSD to ensure that these drugs are safely consumed.展开更多
The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high po...The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high potency and long duration of fentanyl is compounded by the added risks from xylazine,heightening the lethal danger faced by opioid users.Measures such as enhanced surveillance,public awareness campaigns,and the distribution of fentanylxylazine test kits,and naloxone have been undertaken to mitigate this crisis.Fentanyl-related overdose deaths persist despite these efforts,partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies.A multifaceted approach is imperative in effectively combating the opioid overdose epidemic.This approach should include expansion of treatment access,broadening the availability of medications for opioid use disorder,implementation of harm reduction strategies,and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.展开更多
BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatmen...BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatment Program(OTP).METHODS This longitudinal study included 501 patients(81.4%men,median age:45 years;interquartile range:39-50 years)enrolled in an OTP between October 2015 and September 2017.Patients were followed until September 2019.Data on sociodemographics,substance use,HCV infection,human immunodeficiency virus(HIV)infection and laboratory parameters were collected at entry.We analyzed medical records to evaluate HCV treatment.Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTS Prevalence of HCV and HIV infection was 70%and 34%,respectively.Among anti-HCV-positive(n=336)patients,47.2%,41.3%,and 31.9%used alcohol,cannabis,and cocaine,respectively.HCV-RNA tests were positive in 233(69.3%)patients.Twentyeight patients(8.3%)cleared the infection,and 59/308(19.1%)had received interferon-based treatment regimens before 2015.Among 249 patients eligible,111(44.6%)received DAAs.Treatment rates significantly increased over time from 7.8/100 person-years(p-y)(95%CI:5.0-12.3)in 2015 to 18.9/100 p-y(95%CI:11.7-30.3)in 2019.In a multivariate analysis,patients with HIV co-infection were twice as likely to receive DAAs(HR=1.94,95%CI:1.21-3.12)than patients with HCV mono-infection.Current drug use was an independent risk factor for not receiving treatment against infection(HR=0.48,95%CI:0.29-0.80).CONCLUSION HCV treatment is evolving in patients with HCV-HIV co-infection.Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.展开更多
Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders(OUDs).Three long-acting buprenorphine depot or implant formulations are currently available for the tre...Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders(OUDs).Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs:(1)CAM 2038(Buvidal)for subcutaneous weekly and monthly application;(2)RBP-6000(Sublocade^(TM))as a monthly depot formulation;and(3)A six-month buprenorphine implant[Probuphine^(TM)].The pharmacology,clinical efficacy and prospects of these medications are discussed.展开更多
Using the radioreceptor binding assay, μ-opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric...Using the radioreceptor binding assay, μ-opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric administration of the MOR antagonist naloxone methiodide was followed by an increase in the number of MORs in the frontal cortex. However, the MOR agonist loperamide significantly decreased the density of MORs in the frontal cortex and midbrain of naive animals. Loperamide and naloxone methiodide were shown to prevent an increase in MOR affinity and a decrease in MOR density in the midbrain of rats after restraint stress. The restraint stress was accompanied by an increase in the release of β-endorphin (BE) in the ventral tegmental area (VTA) of control rats. After administration, loperamide slightly decreased the release of BE, naloxone methiodide significantly increased the release of BE in the cingulate cortex (CC) of untreated animals, while drugs had no effect on the release of BE in the VTA. The drugs significantly increased the extracellular level of BE in the CC of stressed animals. Loperamide abolished the increase in the stress-induced release of BE in the VTA. By contrast, naloxone methiodide significantly increased the release of BE in the VTA of stressed rats. Our data indicated that activation of peripheral MORs induces depression of the central part of the μ-opioid system, but suppression of peripheral MOR activity induces activation of the central μ-opioid system, the interaction of which can be modulated by stress.展开更多
Objective: To observe the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow transit constipation (STC). Methods: T...Objective: To observe the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow transit constipation (STC). Methods: The cathartic colon model of rat was made by feeding with laxatives. The activity of mu and kappa opioid receptors in the cathartic colon of rat was measured by radio-ligand binding assay. Results: Compared with the control group, the maximal binding capacity (Bmax) and affinity(Kd) of mu opioid receptor in cathartic colon group were significantly increased (207.00±22.90 fmol/mg·p vs 82.00±14.23 fmol/mg·p, P < 0.01;3.30±0.45 mmol/L vs 2.40±0.57 mmol/L,P < 0.05). The maximal binding capacity of kappa opioid receptor also showed a great increase (957.00±102.41 fmol/mg·p vs 459.00±52.41 fmol/mg·p, P<0.01), but no significant difference of affinity was found between the two groups. Conclusion: The mu and kappa opioid receptors may be involved in the functional disorders of cathartic colon.展开更多
30 year old female now para 1 presented to the Emergency Department with nausea, vomiting, and abdominal pain 6 days after an uncomplicated primary cesarean delivery. She did not respond to conservative management and...30 year old female now para 1 presented to the Emergency Department with nausea, vomiting, and abdominal pain 6 days after an uncomplicated primary cesarean delivery. She did not respond to conservative management and underwent exploratory laparotomy for worsening pain, pneumoperitoneum and intraabdominal fluid collections. Gastric perforations required repair via gastrojejunostomy. Postoperative course was unremarkable. The anti-opioid campaign has altered the approach to postoperative pain management in both positive and negative ways. It has sparked new interest in alternative approaches to postoperative pain management, which include an increased role for non-steroidal anti-inflammatory drugs (NSAIDs). We present a case of a woman who had a significant complication due to the reliance of non-opioid pain medications after cesarean delivery.展开更多
Opioid crisis continues to gain ground in the United States with little regards to color or economic status.More than 800 people die weekly from opioid-related overdosestotally well over 42,000 deaths in 2016,and the ...Opioid crisis continues to gain ground in the United States with little regards to color or economic status.More than 800 people die weekly from opioid-related overdosestotally well over 42,000 deaths in 2016,and the number is rising.Surprisingly,the opioid overdose deaths involved an estimated 40%prescription opioid abuse.As reported by the National Drug Institute(2017),opioid addiction is often described as an“equal opportunity”problem that can afflict people from all races and walks of life.Unlike the crack crises of the past,the present opioid epidemic has extremely impacted White Americans not only the rural and poor,but also suburban and middle class or affluent.Further,current opioid overdoses deaths have increased for Whites,Blacks,and Hispanics,they have increased to a far greater degree for White Americans.Efforts to battle the increasing opioid epidemic have moved from incarceration to using legislation to limit the prescriptions being distributed.State and federal laws are being enacted to placing limitations on opioid prescriptions.展开更多
Protein to protein interactions leading to homo/heteromerization of receptor is well documented in literature. These interactions leading to dimeric/oligomers formation of receptors are known to modulate their functio...Protein to protein interactions leading to homo/heteromerization of receptor is well documented in literature. These interactions leading to dimeric/oligomers formation of receptors are known to modulate their function, particularly in case of G-protein coupled receptors. The opioid receptor heteromers having changed pharmacological properties than the constituent protomers provides preferences for novel drug targets that could lead to potential analgesicactivity devoid of tolerance and physical dependence. Heterodimerization of opioid receptors appears to generate novel binding properties with improved specificity and lack of side effects. Further the molecules which can interact simultaneously to both the protomers of the heteromer, or to both the binding sites(orthosteric and allosteric) of a receptor protein could be potential therapeutic molecules. This review highlights the recent advancements in exploring the plausible role of heteromerization of opioid receptors in induction of tolerance free antinociception.展开更多
基金supported by the Russian Science Foundation(Grant No.23-65-10017 to B.K.K.and M.K.)The Ministry of Science and Higher Education of the Russian Federation(Grant No.122020300042-4 to L.N.M.)supported the preparation of the minichapter titled"Opioids reduce inflammatory injury of the heart".
文摘Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.
文摘The US opioid crisis has become a serious public health issue,causing tens of thousands of deaths and tremendous economic loss annually.Acupuncture,as a traditional non-pharmacological method of analgesia,has demonstrated extraor-dinary value in addressing this crisis.This paper systematically elucidates the causes and impacts of the US opioid crisis and deeply explores the neurobiological mechanisms of acupuncture analgesia,including the activation of the endogenous opioid system,neurotransmitter regulation,and anti-inflammatory and immune modulation via multiple pathways.By analyzing the clinical evidence for acupuncture in the management of acute and chronic pain,opioid dosage reduction,and addiction treatment,we demonstrate the feasibility and effi cacy of acupuncture as an alternative to opioid therapy.Research shows that acupuncture can not only eff ectively relieve various types of pain but also reduce opioid consumption and treat opioid dependence and addiction.However,the promotion of acupuncture in the US still faces multi-faceted challenges,including issues of standardization,limited insurance coverage,and insuffi cient high-quality evidence.Future eff orts should focus on strengthening multidisciplinary research collaboration,improving standardized treatment protocols,and integrating acupunc-ture into comprehensive pain management systems to provide a safer,more cost-eff ective,non-pharmacological alternative for resolving the opioid crisis.
文摘BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question is“How does the use of opioid medications in pain management,compared with non-opioid medications,affect pain intensity over the short,intermediate,and long-term in adults with acute traumatic pain?”.METHODS The protocol was prospectively registered on the International Prospective Re-gister of Systematic Reviews:CRD42021279639.Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full,with the PICO framework:P:Adult patients with traumatic injuries,I:Opioid medications,C:Non-opioid medi-cations,O:A minimum clinically important difference(MCID)in pain.RESULTS After full-text screening,we included 14 studies in the qualitative synthesis.Of these 14 studies,12 were rando-mized clinical trials(RCTs)and 2 were pseudo-RCTs with a total of 2347 patients enrolled.There was heteroge-neity in both medication utilized and outcome in these studies;only two studies were homogeneous regarding the type of study conducted,the opioid used,its comparator,and the outcome explored.The MCID was evaluated in 8 studies,while in 6 studies,any measured pain reduction was considered as an outcome.In 11 cases,the setting of care was the Emergency Department;in 2 cases,care occurred out-of-hospital;and in one case,the setting was not well-specified.The included studies were found to have a low-moderate risk of bias.CONCLUSION Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury.Intravenous ketamine may cause more adverse events than other routes of administration.
基金Supported by Wu Jieping Foundation,No.320.6750.2024-05-55.
文摘Gastrointestinal endoscopy is a common examination for digestive system.The stimulation of endoscope often causes cough,nausea and vomiting,increased heart rate and blood pressure,arrhythmia,and even cardiovascular and cerebrovascular accidents,thus makes people fear of this procedure.Sedation or anesthesia can effectively improve the safety,comfort and quality of gastrointestinal endoscopy.A small dose of opioids is a good adjuvant to sedatives.In this narrative review,we summarized the main roles of opioid analgesics in gastrointestinal endoscopy,including reducing visceral pain,throat irritation and the dose of sedatives.Moreover,the frequently used and novel opioids are reviewed.Classic fentanyl,sufentanil and dezocine are preferable by anesthesiologists.Newly approved oliceridine is promising to render ideal analgesic effects for gastrointestinal endoscopy.Clinical studies on oliceridine in endoscopic procedures are urgently needed.
基金supported by the National Natural Science Foundation of China(32271047)the National Key Research and Development Program of China(2020YFC2008405)+1 种基金The Innovative Research Team of High-level Local Universities in Shanghai,the Natural Science Foundation of Shanghai(22ZR1413800)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)。
文摘Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic basis for variable itch incidence remains unknown.This study examined 3616 patients receiving epidural opioids,revealing an itch occurrence of 26.55%,with variations among opioid types and gender.Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms,notably rs1799971(A118G),that correlated with opioid-induced itch.Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch,mirroring human findings.The 118G allele demonstrated an anti-itch effect without impacting analgesia,addiction,or tolerance,offering insights for risk stratification and potential anti-itch pretreatment strategies.
文摘BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.
基金Supported by the National Natural Science Foundation of China:81574078。
文摘Objectives Retinal ischemia-reperfusion(RIR)injury results in irreversible visual impairments.The disruption of the outer blood-retinal barrier(OBRB)is a major ocular pathogenic process that RIR injury affects.Current clinical strategies are limited.This study aimed to elucidate how electroacupuncture(EA)protects the OBRB against RIR injury.Methods Male Wistar rats(7 weeks old,250 g to 280 g)were used in this study.Three independent experiments were conducted.First,Opioid peptide levels were quantified using enzyme-linked immunosorbent assay(ELISA).42 rats were randomly divided into 7 groups(n=6/group):Control:No treatment;high intraocular pressure(HIOP):Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming(Extra acupoint)and Jingming(BL1)for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;HIOP+100 Hz:RIR injury+100 Hz EA at Xinming and BL1 for 30 min;HIOP+2/100 Hz EA:RIR injury+2/100 Hz EA at Xinming and BL1 for 30 min;HIOP+4/20 Hz EA:RIR injury+4/20 Hz EA at Xinming and BL1 for 30 min.Second,retinal morphology was assessed by hematoxylin and eosin(HE)staining.20 rats were randomly allocated into 4 groups(n=5/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min.Third,the permeability of OBRB was evaluated using the fluorescein isothiocyanate(FITC)-dextran leakage assay.15 rats were randomly divided into 5 groups(n=3/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;Nal+HIOP+2 Hz EA:Intravitreal injection ofδ-opioid receptor antagonist Naltridole(10µl,100 nM)30 min before RIR injury induction,followed by 2 Hz EA treatment at Xinming and BL1 for 30 min.In vitro studies examined enkephalins'effects on oxygen–glucose deprivation/reperfusion(OGD/R)induced injury in ARPE‐19 cells.Cell viability was evaluated by cell counting kit-8(CCK-8)assay,and morphological changes were recorded by Molecular Devices.Apoptosis was detected by Annexin V-FITC flow cytometry.Delta opioid receptor(DOR)expression in total protein and membrane protein were analyzed by western blotting(WB).Immunofluorescence(IF)staining and WB assessed ZO-1 and Claudin-19.For cell-based assays,n indicates the number of biologically independent replicates.Results It was found that 2 Hz EA treatment increased enkephalins(methionine-enkephalin and leucine-enkephalin)levels(P<0.01),restoring the increased retinal thickness(P<0.05)and mitigating RGCs loss(P<0.05)post-RIR injury.FITC-dextran leakage in the outer retina was ameliorated by 2 Hz EA(P<0.05),reversibly countered by Naltrindole(P<0.05),a DOR antagonist.Treatment with 30µM enkephalins enhanced ARPE-19 cell viability(P<0.001,P<0.0001)and inhibited apoptosis(P<0.0001).Enkephalins elevated DOR levels in total protein(P<0.05)and membrane protein fractions(P<0.001,P<0.0001),as well as elevated ZO-1(P<0.001,P<0.01)and Claudin-19(P<0.0001,P<0.001)levels following OGD/R,counteracted by Naltrindole.Conclusion It was found that 2 Hz EA inhibits the breakdown of OBRB via enkephalins activate DOR in RIR injury.
基金Supported by the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘In this article,we evaluate the findings of the study by Qian et al,which explores the efficacy of combining hyperthermia with opioid therapy for enhanced cancer pain management in patients with middle and late-stage gastrointestinal tumors.The study undertakes a retrospective analysis comparing traditional opioid therapy to an integrated approach of hyperthermia and opioids across 70 patients,highlighting significant benefits in pain control,reduction of opioid dosage,and minimization of adverse reactions.In our article,we not only discuss these fin-dings but also emphasize the broader implications for clinical practice,parti-cularly in enhancing patient outcomes through innovative pain management strategies.We advocate for further research to establish more robust data su-pporting this approach and to explore the mechanistic insights that enable these benefits.This discussion reflects on the potential paradigm shift in managing debilitating cancer-related pain,urging a reevaluation of current practices to incorporate these findings effectively.
文摘1.The development history of enhanced recovery after surgery(ERAS)Enhanced recovery after surgery(ERAS)is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception.In 1997,Professor Henrik Kehlet,also known as the“father of ERAS”,from the University of Copenhagen in Denmark first proposed the ERAS concept and discovered its clinical feasibility and superiority,achieving remarkable results.ERAS was initially applied in colorectal surgery;subsequently,the concept gradually gained popularity and application worldwide.
文摘Patients with chronic pancreatitis often experience severe,unrelenting abdominal pain,which can significantly impact their quality of life.Pain control,therefore,remains central to the overall management of chronic pancreatitis.Most of the strategies aimed at treating the pain of chronic pancreatitis are based on expert opinion and vary from one institution to another,as there are no uniform guidelines to direct a stepwise approach towards achieving this goal.In this editorial,we comment on best practice strategies targeted towards pain control in chronic pancreatitis,specifically highlighting the use of opioid medications in this patient population.We discuss various safe and efficacious prescription monitoring practices in this article.
文摘BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with PTSD than those without this disorder.AIM To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and Outcomes(PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical analysis.RESULTS A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and neck pain(28.7%;range: 3.6%-63%). In total,42.4% of the participants across studies had a diagnosis of PTSD(range: 4.7%-95%). In relation to opioid intake, we identified 2 different outcomes: opioid prescription and OUD. All the studies reported evidence of a greater prevalence of PTSD in CNCP patients who were receiving prescribed opioids and that PTSD was associated with OUD in CNCP patients.CONCLUSION Opioid analgesic prescription as the treatment of choice for CNCP patients should include screening for baseline PTSD to ensure that these drugs are safely consumed.
文摘The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high potency and long duration of fentanyl is compounded by the added risks from xylazine,heightening the lethal danger faced by opioid users.Measures such as enhanced surveillance,public awareness campaigns,and the distribution of fentanylxylazine test kits,and naloxone have been undertaken to mitigate this crisis.Fentanyl-related overdose deaths persist despite these efforts,partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies.A multifaceted approach is imperative in effectively combating the opioid overdose epidemic.This approach should include expansion of treatment access,broadening the availability of medications for opioid use disorder,implementation of harm reduction strategies,and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.
基金Supported by the Ministry of Science,Innovation and Universities,CarlosⅢHealth Institute(ISCⅢ),European Fund for Regional Development(FEDER),Network for Cooperative Research in Health(RETICS),Spain(No.RD16/0017/0003,PI17/00174,INT19/00026,CD19/00019)the Ministry of Health,National Plan on Drugs(PNSD),Spain(No.2018/020)+4 种基金the European Commission(806996-JUSTSO-JUST2017-AG-DRUG)the Gilead Fellowship Program,Gilead Sciences(No.GLD17/187)the Ministry of Education,Spain(No.PRX18/00245)the Agency for Management of University and Research Grants,Government of Catalonia(No.2017SGR316)and the Municipal Institute of Personal。
文摘BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatment Program(OTP).METHODS This longitudinal study included 501 patients(81.4%men,median age:45 years;interquartile range:39-50 years)enrolled in an OTP between October 2015 and September 2017.Patients were followed until September 2019.Data on sociodemographics,substance use,HCV infection,human immunodeficiency virus(HIV)infection and laboratory parameters were collected at entry.We analyzed medical records to evaluate HCV treatment.Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTS Prevalence of HCV and HIV infection was 70%and 34%,respectively.Among anti-HCV-positive(n=336)patients,47.2%,41.3%,and 31.9%used alcohol,cannabis,and cocaine,respectively.HCV-RNA tests were positive in 233(69.3%)patients.Twentyeight patients(8.3%)cleared the infection,and 59/308(19.1%)had received interferon-based treatment regimens before 2015.Among 249 patients eligible,111(44.6%)received DAAs.Treatment rates significantly increased over time from 7.8/100 person-years(p-y)(95%CI:5.0-12.3)in 2015 to 18.9/100 p-y(95%CI:11.7-30.3)in 2019.In a multivariate analysis,patients with HIV co-infection were twice as likely to receive DAAs(HR=1.94,95%CI:1.21-3.12)than patients with HCV mono-infection.Current drug use was an independent risk factor for not receiving treatment against infection(HR=0.48,95%CI:0.29-0.80).CONCLUSION HCV treatment is evolving in patients with HCV-HIV co-infection.Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.
文摘Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders(OUDs).Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs:(1)CAM 2038(Buvidal)for subcutaneous weekly and monthly application;(2)RBP-6000(Sublocade^(TM))as a monthly depot formulation;and(3)A six-month buprenorphine implant[Probuphine^(TM)].The pharmacology,clinical efficacy and prospects of these medications are discussed.
文摘Using the radioreceptor binding assay, μ-opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric administration of the MOR antagonist naloxone methiodide was followed by an increase in the number of MORs in the frontal cortex. However, the MOR agonist loperamide significantly decreased the density of MORs in the frontal cortex and midbrain of naive animals. Loperamide and naloxone methiodide were shown to prevent an increase in MOR affinity and a decrease in MOR density in the midbrain of rats after restraint stress. The restraint stress was accompanied by an increase in the release of β-endorphin (BE) in the ventral tegmental area (VTA) of control rats. After administration, loperamide slightly decreased the release of BE, naloxone methiodide significantly increased the release of BE in the cingulate cortex (CC) of untreated animals, while drugs had no effect on the release of BE in the VTA. The drugs significantly increased the extracellular level of BE in the CC of stressed animals. Loperamide abolished the increase in the stress-induced release of BE in the VTA. By contrast, naloxone methiodide significantly increased the release of BE in the VTA of stressed rats. Our data indicated that activation of peripheral MORs induces depression of the central part of the μ-opioid system, but suppression of peripheral MOR activity induces activation of the central μ-opioid system, the interaction of which can be modulated by stress.
文摘Objective: To observe the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow transit constipation (STC). Methods: The cathartic colon model of rat was made by feeding with laxatives. The activity of mu and kappa opioid receptors in the cathartic colon of rat was measured by radio-ligand binding assay. Results: Compared with the control group, the maximal binding capacity (Bmax) and affinity(Kd) of mu opioid receptor in cathartic colon group were significantly increased (207.00±22.90 fmol/mg·p vs 82.00±14.23 fmol/mg·p, P < 0.01;3.30±0.45 mmol/L vs 2.40±0.57 mmol/L,P < 0.05). The maximal binding capacity of kappa opioid receptor also showed a great increase (957.00±102.41 fmol/mg·p vs 459.00±52.41 fmol/mg·p, P<0.01), but no significant difference of affinity was found between the two groups. Conclusion: The mu and kappa opioid receptors may be involved in the functional disorders of cathartic colon.
文摘30 year old female now para 1 presented to the Emergency Department with nausea, vomiting, and abdominal pain 6 days after an uncomplicated primary cesarean delivery. She did not respond to conservative management and underwent exploratory laparotomy for worsening pain, pneumoperitoneum and intraabdominal fluid collections. Gastric perforations required repair via gastrojejunostomy. Postoperative course was unremarkable. The anti-opioid campaign has altered the approach to postoperative pain management in both positive and negative ways. It has sparked new interest in alternative approaches to postoperative pain management, which include an increased role for non-steroidal anti-inflammatory drugs (NSAIDs). We present a case of a woman who had a significant complication due to the reliance of non-opioid pain medications after cesarean delivery.
文摘Opioid crisis continues to gain ground in the United States with little regards to color or economic status.More than 800 people die weekly from opioid-related overdosestotally well over 42,000 deaths in 2016,and the number is rising.Surprisingly,the opioid overdose deaths involved an estimated 40%prescription opioid abuse.As reported by the National Drug Institute(2017),opioid addiction is often described as an“equal opportunity”problem that can afflict people from all races and walks of life.Unlike the crack crises of the past,the present opioid epidemic has extremely impacted White Americans not only the rural and poor,but also suburban and middle class or affluent.Further,current opioid overdoses deaths have increased for Whites,Blacks,and Hispanics,they have increased to a far greater degree for White Americans.Efforts to battle the increasing opioid epidemic have moved from incarceration to using legislation to limit the prescriptions being distributed.State and federal laws are being enacted to placing limitations on opioid prescriptions.
基金Supported by Council of Scientific and Industrial Research
文摘Protein to protein interactions leading to homo/heteromerization of receptor is well documented in literature. These interactions leading to dimeric/oligomers formation of receptors are known to modulate their function, particularly in case of G-protein coupled receptors. The opioid receptor heteromers having changed pharmacological properties than the constituent protomers provides preferences for novel drug targets that could lead to potential analgesicactivity devoid of tolerance and physical dependence. Heterodimerization of opioid receptors appears to generate novel binding properties with improved specificity and lack of side effects. Further the molecules which can interact simultaneously to both the protomers of the heteromer, or to both the binding sites(orthosteric and allosteric) of a receptor protein could be potential therapeutic molecules. This review highlights the recent advancements in exploring the plausible role of heteromerization of opioid receptors in induction of tolerance free antinociception.
