Hormone Replacement Therapy for Restoring the HPG Axis in Pain Patients Treated with Long-Term Opioid Analgesics

Opioids are a treatment option for a variety of chronic pain conditions. But long-term opioid use can be associated with side effects, including hypogonadism. Opioid-induced hypogonadism (OIhG) is associated with the alteration of the hypothalamic-pituitary-gonadal axis (HPG). In males, hypogonadism can result in erectile dysfunction, reduced libido, fatigue, worsening mood, and increased risk of osteoporosis;in females, it can result in changes in the menstrual cycle and reduced libido, among other effects. A current treatment option for these patients is hormone replacement therapy. In this report, we discuss the problem of opioid-induced hypogonadism, and the therapeutic approach and the potential complications of treating pain patients using hormone replacement therapy.

The Effectiveness of Ketamine Compared to Opioid Analgesics for Management of Acute Pain in Children in the Emergency Department: Systematic Review

Background: Ketamine is increasingly being used as an alternative to opioids in the management of acute pain in the emergency department. In turn, there is increasing research attention to prove the efficacy of ketamine as an analgesic in children presenting in the emergency department. Objective: The first objective of this systematic review was to investigate the effectiveness of ketamine compared to opioid analgesics for pain management in children aged two months to 18 years who have acute pain in the emergency department. The second objective was to compare the adverse events and side effects associated with ketamine with those associated with opioids used for pain management. Methods: A systematic review, using the JBI systematic review was completed. A computerised search from five databases;CINAHL, EMBASE, EMCARE and PubMed, and Cochrane. The included studies were appraised by JBI critical appraisal tool for randomised controlled trials and the study results analysed. Findings: Four randomised control trial studies were included in this systematic review. All the included studies compared ketamine with opioids (morphine and fentanyl) for the management of severe pain in children. The studies were of high methodological quality based on JBI critical appraisal outcome. Meta-analysis was not possible because of the heterogeneity of the studies, especially in terms of different outcome measures, and the approaches (pain assessment tool) used to measure the pain outcomes. The review identified that ketamine demonstrated a non-inferior analgesia effect compared to opioid medication (morphine or fentanyl) as determined by various pain scores used in different studies. However, ketamine use was associated with increased frequency of occurrence of temporary adverse effects that do not require clinical attention. Conclusion: Based on the findings from the review, ketamine is a suitable alternative for opioid analgesics for the management of acute and severe pain in children in ED. The minor transient side effects associated with ketamine should not limit the use of ketamine. Future studies should investigate the appropriate dosage and route of administration of ketamine to be used while managing pain among children with acute and severe pain in the emergency department.

Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain

Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.

Fentanyl and xylazine crisis:Crafting coherent strategies for opioid overdose prevention

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.

Exploring the Contribution of Pharmacists in Addressing the Opioid Crisis through Naloxone Prescriptions and Pharmacist-Led Interventions

The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opioid overdoses. Pharmacists play an important role in the accessibility and education of naloxone in both the community and health system settings. Recent efforts, such as co-dispensing naloxone with opioid prescriptions, naloxone training programs, and approval of naloxone to be over-the-counter, have been implemented in hopes to better control the opioid epidemic. Despite the efforts to make naloxone more accessible, there are still some barriers to overcome such as lack of training, cost, stigma, and patient refusal. This review aims to explore the contributions pharmacists have made thus far and define the barriers that still have to be resolved.

The Impact of Opioid Drugs on Memory and Other Cognitive Functions: A Review

Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.

Quasi-Static, Poiseuille Flow of Analgesics from an Elastomeric Pump: Theoretical Determination of Infusion Times and Toxicity Conditions

Background: Elastomeric pumps (elastic balls into which analgesics or antibiotics can be inserted) push medicines through a catheter to a nerve or blood vessel. Since elastomeric pumps are small and need no power source, they fit easily into a pocket during infusion, allowing patient mobility. Elastomeric pumps are widely used and widely studied experimentally, but they have well-known problems, such as maintaining reliable flow rates and avoiding toxicity or other peak-and-trough effects. Objectives: Our research objective is to develop a realistic theoretical model of an elastomeric pump, analyze its flow rates, determine its toxicity conditions, and otherwise improve its operation. We believe this is the first such theoretical model of an elastomeric pump consisting of an elastic, medicine-filled ball attached to a horizontal catheter. Method: Our method is to model the system as a quasi-Poiseuille flow driven by the pressure drop generated by the elastic sphere. We construct an engineering model of the pressure exerted by an elastic sphere and match it to a solution of the one-dimensional radial Navier-Stokes equation that describes flow through a horizontal, cylindrical tube. Results: Our results are that the model accurately reproduces flow rates obtained in clinical studies. We also discover that the flow rate has an unavoidable maximum, which we call the “toxicity bump”, when the radius of the sphere approaches its terminal, unstretched value—an effect that has been observed experimentally. Conclusions: We conclude that by choosing the properties of an elastomeric pump, the toxicity bump can be restricted to less than 10% of the earlier, relatively constant flow rate. Our model also produces a relation between the length of time that the analgesic fluid infuses and the physical properties of the fluid, of the elastomeric sphere and the tube, and of the blood vessel into which the analgesic infuses. From these, we conclude that elastomeric pumps can be designed, using our simple model, to control infusion times while avoiding toxicity effects.

Pain management in acute musculoskeletal injury: Effect of opioid vs nonopioid medications

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.

Adaptive Modeling of Monthly Depression Levels in Terms of Daily Assessments of Opioid Medications Taken and Pain Levels for Cancer Patients

A research study collected intensive longitudinal data from cancer patients on a daily basis as well as non-intensive longitudinal survey data on a monthly basis. Although the daily data need separate analysis, those data can also be utilized to generate predictors of monthly outcomes. Alternatives for generating daily data predictors of monthly outcomes are addressed in this work. Analyses are reported of depression measured by the Patient Health Questionnaire 8 as the monthly survey outcome. Daily measures include numbers of opioid medications taken, numbers of pain flares, least pain levels, and worst pain levels. Predictors are averages of recent non-missing values for each daily measure recorded on or prior to survey dates for depression values. Weights for recent non-missing values are based on days between measurement of a recent value and a survey date. Five alternative averages are considered: averages with unit weights, averages with reciprocal weights, weighted averages with reciprocal weights, averages with exponential weights, and weighted averages with exponential weights. Adaptive regression methods based on likelihood cross-validation (LCV) scores are used to generate fractional polynomial models for possible nonlinear dependence of depression on each average. For all four daily measures, the best LCV score over averages of all types is generated using the average of recent non-missing values with reciprocal weights. Generated models are nonlinear and monotonic. Results indicate that an appropriate choice would be to assume three recent non-missing values and use the average with reciprocal weights of the first three recent non-missing values.

Personalized medicine and opioid use disorder

Opioid use disorder(OUD)is a major public health problem affecting millions of people worldwide.Although OUD is a chronic and relapsing disorder,a variety of pharmacological and non-pharmacological interventions are available.Medication-assisted treatment of OUD generally relies on competition for opioid receptors against the addictive substance.The mechanisms of this competition are to block or inactivate the opioid receptor or activate the receptor with a substance that is intermittent or long acting.Methadone and buprenorphine are two United States Food and Drug Administration-approved medications that have long-term positive effects on the health of opioid-dependent individuals.Although clinical studies of drugs generally demonstrate efficacy in thousands of people and toxicity is excluded,it cannot be predicted whether the given drug will cause side effects in one of the patients at the treatment dose.Individual differences can be explained by many biological and environmental factors.Variations in genes encoding drug metabolism or cellular drug targets significantly explain the variability in drug response between individuals.Therefore,for the effects of candidate genes to be accepted and included in individual treatment protocols,it is important to repeat studies on individuals of different ethnic backgrounds and prove a similar effect.

Effect of hyperthermia combined with opioids on cancer pain control and surgical stress in patients with gastrointestinal cancer

BACKGROUND Surgical palliative surgery is a common method for treating patients with middle and late stage gastrointestinal tumors.However,these patients generally expe-rience high levels of cancer pain,which can in turn stimulate the body’s stress and undermine the effect of external surgery.Although opioid drugs have a signifi-cantly positive effect on controlling cancer pain,they can induce adverse drug reactions and potential damage to the body’s immune function.Hyperthermia therapy produces a thermal effect that shrinks tumor tissues.However,its effect on relieving the pain of middle and late stage gastrointestinal tumors but also the stress of surgical palliative surgery remains unclear.AIM To investigate the effect of hyperthermia combined with opioids on controlling cancer pain in patients with middle and late stage gastrointestinal cancer and evaluate its impact on surgical palliative surgical stress.METHODS This was a retrospective study using the data of 70 patients with middle and late stage gastrointestinal tumors who underwent cancer pain treatment and surgical palliative surgery in the Ninth People’s Hospital of Suzhou,China from January 2021 to June 2024.Patients were grouped according to different cancer pain control regimens before surgical palliative surgery,with n=35 cases in each group,as follows:Patients who solely used opioid drugs to control cancer pain were included in Group S,while patients who received hyperthermia treatment combined with opioid drugs were included in Group L.In both groups,we compared the effectiveness of cancer pain control(pain score,burst pain score,24-hour burst pain frequency,immune function,daily dosage of opioid drugs,and adverse reactions),surgical palliative indicators(surgery time,intraoperative bleeding,stress response),and postoperative recovery time,including first oral feeding time,postoperative hospital stay).RESULTS Analgesic treatment resulted in a significant decrease in the average pain score,burst pain score,and 24-hour burst pain frequency in both Groups L and S;however,these scores were statistically significantly lower in Group L than in Group S group(P<0.001).Analgesic treatment also resulted in significant differences,namely serum CD4+(29.18±5.64 vs 26.05±4.76,P=0.014),CD8+(26.28±3.75 vs 29.23±3.89,P=0.002),CD4+/CD8+(0.97±0.12 vs 0.83±0.17,P<0.001),between Group L and Group S,respectively.The daily dosage of opioid drugs incidence of adverse reactions such as nausea,vomiting,constipation,and difficulty urinating were statistically significantly lower in Group L than those in group S(P<0.05).Furthermore,palliative surgery time and intraoperative blood loss in Group L were slightly lower than those in Group S;however,the difference was not statistically significant(P>0.05).On the first day after surgery,serum cortisol and C-reactive protein levels of patients in group L and group S were 161.43±21.07 vs 179.35±27.86 ug/L(P=0.003)and 10.51±2.05 vs 13.49±2.17 mg/L(P<0.001),respectively.Finally,the first oral feeding time and hospitalization time after surgery in group L were statistically significantly shorter than those in group S(P<0.05).CONCLUSION Our findings showed that hyperthermia combined with opioids is effective in controlling cancer pain in patients with middle and late stage gastrointestinal tumors.Furthermore,this method can reduce the dosage of opioids used and minimize potential adverse drug reactions,reduce the patient’s surgical palliative surgical stress response,and shorten the overall postoperative recovery time required.

Cardiovascular Risk of Opioids: A Real-World Study Based on FAERS

Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.

Pain management in chronic pancreatitis incorporating safe opioid practices: Challenge accepted

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.

Changes of mu and kappa opioid receptors in cathartic colon of rat

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.

Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

AIM:To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture(EA) and whether EA effect was mediated by endogenous opiates.METHODS:Six to nine week-old male SpragueDawley rats were used in this study.Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress(HIS) protocol composed of 3 randomly stressors,which included cold restraint stress at 4?℃ for 45 min,water avoidance stress for 60 min,and forced swimming stress for 20 min,in adult male rats.The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex(AWR) scores of colorectal distension at different distention pressures(20 mmHg,40 mmHg,60 mmHg and 80 mmHg).AWR scores either 0,1,2,3 or 4 were obtained by a blinded observer.EA or sham EA was performed at classical acupoint ST-36(Zu-San-Li) or BL-43(Gao-Huang) in both hindlimbs of rats for 30 min.Naloxone(NLX) or NLX methiodide(m-NLX) was administered intraperitoneally to HIS rats in some experiments.RESULTS:HIS rats displayed an increased sensitivity to colorectal distention,which started from 6 h(the first measurement),maintained for 24 h,and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures.The AWR scores before HIS were 0.6 ± 0.2,1.3 ± 0.2,1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg distention pressures,respectively.Six hours after termination of the last stressor,the AWR scores were 2.0 ± 0.1,2.5 ± 0.1,2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg distention pressures,respectively.EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg:2.0 ± 0.2 vs 0.7 ± 0.1,P = 4.23 711 E-4;AWRs at 40 mmHg:2.6 ± 0.2 vs 1.5 ± 0.2,P = 0.00 163;AWRs at 60 mmHg:3.1 ± 0.2 vs 1.9 ± 0.1,P = 0.003;AWRs at 80 mmHg:3.6 ± 0.1 vs 2.4 ± 0.2,P = 0.0023;electromyographic(EMG) at 20 mmHg:24 ± 4.7 vs 13.8 ± 3.5;EMG at 40 mmHg:60.2 ± 6.6 vs 30 ± 4.9,P = 0.00 523;EMG at 60 mmHg:83 ± 10 vs 39.8 ± 5.9,P = 0.00 029;EMG at 80 mmHg:94.3 ± 10.8 vs 49.6 ± 5.9,P = 0.00 021].In addition,EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats.EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressuresof 20 and 40 mmHg.The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline(NS) were 2.0 vs 0.70 ± 0.20,2.80 ± 0.12 vs 1.50 ± 0.27,3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg;P = 0.0087,0.0104,0.0117 and 0.0188 for 20,40,60 and 80 mmHg,respectively].Furthermore,EA-mediated analgesic effect was completely reversed by administration of m-NLX,a peripherally restricted opioid antagonist(EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88,74.16 ± 9.04 vs 36.28 ± 8.01,96.45 ± 11.80 vs 50.19 ± 8.28,and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg;P = 0.05 026,0.00 034,0.00 005,0.000 007 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg,respectively).CONCLUSION:EA given at classical acupoint ST-36 alleviates stress-induced visceral pain,which is most likely mediated by opioid pathways in the periphery.

Design, Synthesis of Analgesics and Anticancer of Some New Derivatives of Benzimidazole

This work, contains some new compounds from benzimidazole derivatives, which are synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting in 2-Mercapto-benzimidazole which is treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chloroacetates, chloroacetic chloride, alkyl halides) also the ethoxy carbonyl methyl thiobenzimidazole reacts with different amines. In addition to chloromethyl benzimidazole which resulted from the reaction between orthophenylene diamine and chloroacetic acid, which reacted with different amines. The synthesized compound tested as analgesics and anticancer activity the new derivatives revealed moderate, strong and very strong analgesics and moderate and strong anticancer activity.

Cirrhosis-induced morphological changes in the retina:possible role of endogenous opioid

·AIM: To investigate the impact of cirrhosis on retinal morphology and to evaluate the role of endogenous opioids as a mediator in cirrhosis induced retinal change.·METHODS: Thirty-six male rats were divided into 3main groups; the common bile duct ligated(BDL) group,the sham-operated(Sham) group and the unoperated(Unop) group. Then each of these three main groups was divided into two subgroups; the first subgroup received daily injection of naltrexone hydrochloride(NTX) and the second group was injected with normal saline(Saline)daily. After 28 d, rats were anesthetized and their right eyes were enucleated and assessed for histological changes. The thickness of the rod and cons layer, outer nuclear layer, outer plexiform layer, inner nuclear layer,inner plexiform layer and ganglion cell layer for each eye were measured in micrometers by light microscope.· RESULTS: Ganglion cell layer showed significant increase in thickness in the BDL group(P 【0.05). This increase was eliminated in the group where BDL rats received daily intraperitoneal injection of naltrexone hydrochloride(20 mg/kg). No other histological changes were detected in the other 5 layers we measured·CONCLUSION: The morphological change we detected in the retina of cirrhotic rats is probably due to opioids increased tone in cirrhosis since the increase in thickness in the ganglion cell layer was almost eliminated when naltrexone hydrochloride was injected.These results suggest a possible role for endogenous opioids in the morphological retinal changes detected in cirrhotic rats.

Corelation Between Single Nucleotide Polymorphisms in Mu Opioid Receptor Exon 2 and Stereotypic Behaviour in Sows

Three breeds of sows were observed to investigate the relationship between Single Nucleotide Polymorphisms（SNPs） in Mu Opioid Receptor（MOR）and stereotypic behaviour,such as,sham-chewing,bar biting and standing still in order to better understand the mechanism of stereotypic development of the animals in restrained conditions.MOR exon 2 partial sequences were amplified to analyze single nucleotide polymorphisms by PCR-SSCP.One SNP,a silence mutant was found.A significant difference （P〈0.01）was found in the frequency of genotypes in these 3 breeds where only the BB genotype,which was identical to that published in GenBank,was found in the Duroc breed,while no AA genotype was found in Landrace,3 genotypes AA,BB and AB were found in Yorkshire.The result also indicated that the individuals with AA and AB genotypes tended to be more active in sham-chewing than those with the BB genotype（P〈0.05）.The overall results of this study suggested that sham-chewing of sows may be subjected to both genetic control and environmental conditions,but activity level was more likely to be affected by their environment.We can putatively draw the conclusion that MOR gene has effect on the sham-chewing behavioral traits of sow.

Research Progresses in Effects of Analgesics and Sedatives on Intracranial Pressure of Neurointensive Care Patients

At present, there are some concerns and problems to treat neurointensive care patients by using analgesics and sedatives. Conditions of neurointensive care patients change quickly. For neurointensive care patients who cannot have auxiliary examination timely, clinicians judge intracranial conditions mainly through relevant monitoring devices and consciousness and pupil changes of patients. The use of analgesics and sedatives is limited due to worry about influences on consciousness evaluation and judgment and different degrees of inhibition on cardiovascular system and respiratory system. Common sedatives (e.g. benzodiazepines) and common analgesics (e.g. morphine, fentanyl and sufentanil) both may inhibit respiration. The specification often provides taboos for the use of drugs by patients with increase intracranial pressure (ICP) and craniocerebral injuries. Through literature review, the author analyzed influences of analgesics and sedatives on ICP of neurointensive care patients comprehensively.

Emergency medicine providers＇ opioid prescribing practices stratified by gender, age, and years in practice

BACKGROUND: Emergency medicine providers(EMPs) prescribe about 25% of opioids, but the effect of EMP risk perception on decisions to prescribe opioids is unknown. This study was undertaken to identify factors that infl uence EMP risk and opioid prescribing practices.METHODS: We distributed an anonymous questionnaire to EMPs at a military trauma and referral center. Response frequencies and distributions were assessed for independence using the Chi-square test.RESULTS: Eighty-nine EMPs completed the questionnaire(100% response). Respondents were primarily younger male physicians(80%) in practice under fi ve years(55%). Male EMPs were more likely to prescribe more opioid tablets than female ones both when and when not concerned for opioid misuse(P<0.001, P<0.007, respectively). Of the providers, 70% stated that patient age would inf luence their prescribing decisions. Hydrocodone and oxycodone were the opioids prescribed most frequently. About 60% of the providers reported changing their prescribing behavior would not prevent opioid misuse. Additionally, 40% of the providers believed at least 10% of patients seen at this military ED misused opioids.CONCLUSION: Female EM providers reported prescribing fewer opioid tablets. Patient age infl uenced prescribing behavior, but the effect is unknown. Finally, EM providers reported that altering their prescribing behavior would not prevent prescription opioid misuse.