Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select ...Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select novel targets for which there is proof of clinical relevance, either genetically through heritable traits, or pharmacolog- ically. Such an approach by definition yields targets with high clinical validity. The biology of these targets can be elucidated in animal models before returning to the patients with a refined therapeutic. For optimal treatment, having biomarkers of drug action available is also a plus. Here we describe a case study in rational drug design： the use of controlled inhibition of peripheral tetrahydrobiopterin （BH4） synthesis to reduce abnormal chronic pain states without altering nociceptive-protective pain. Initially iden- tified in a population of patients with low back pain, the association between BH4 production and chronic pain has been confirmed in more than 12 independent cohorts, through a common haplotype （present in 25% of Cau- casians） of the rate-limiting enzyme for BH4 synthesis, GTP cyclohydrolase 1 （GCH1）. Genetic tools in mice have demonstrated that both injured sensory neurons and activated macrophages engage increased BH4 synthesis to cause chronic pain. GCH1 is an obligate enzyme for de novo BH4 production. Therefore, inhibiting GCH1 activity eliminates all BH4 production, affecting the synthesis of multiple neurotransmitters and signaling molecules and interfering with physiological function. In contrast, target- ing the last enzyme of the BH4 synthesis pathway, sepiapterin reductase （SPR）, allows reduction of patholog- ical BH4 production without completely blocking physio- logical BH4 synthesis. Systemic SPR inhibition in mice has not revealed any safety concerns to date, and available genetic and pharmacologic data suggest similar responses in humans. Finally, because it is present in vivo only when SPR is inhibited, sepiapterin serves as a reliable biomarker of target engagement, allowing potential quantification of drug efficacy. The emerging development of therapeutics that target BH4 synthesis to treat chronic pain illustrates the power of combining human and mouse genetics： human genetic studies for clinical selection of relevant targets, coupled with causality studies in mice, allowing the rational engineering of new analgesics.展开更多
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...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.展开更多
T<span style="font-family:Verdana;">his work, contain<span style="font-family:Verdana;">s<span style="font-family:Verdana;"> some new compounds from benzimidazole deriva...T<span style="font-family:Verdana;">his work, contain<span style="font-family:Verdana;">s<span style="font-family:Verdana;"> some new compounds from benzimidazole derivatives, which <span style="font-family:Verdana;">are <span style="font-family:Verdana;">synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting <span style="font-family:Verdana;">in <span style="font-family:Verdana;">2-Mercapto-benzimidazole which <span style="font-family:Verdana;">is <span style="font-family:Verdana;">treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chlo<span style="font-family:Verdana;">roacetates, 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<span style="font-family:Verdana;">.展开更多
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...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.展开更多
Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the acti...Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.展开更多
Introduction: Usage of over-the-counter (OTC) analgesic has increased among Norwegian adolescents since 2001. It has been noted that females tend to have a higher usage compared to males. In this paper we explore this...Introduction: Usage of over-the-counter (OTC) analgesic has increased among Norwegian adolescents since 2001. It has been noted that females tend to have a higher usage compared to males. In this paper we explore this gender difference. Data: Our dataset consists of 284,674 from Norwegian adolescents attending junior high school and high school between 2014 and 2017. Methods: The econometric approach consists of applying ordered logistic regressions with usage of OTC analgesics as the dependent variable and a dichotomous gender variable as the independent variable. Control variables include variables such as frequency of physical and mental health problems and other sociodemographic variables. Results: Gender, physical and mental health problems and various sociodemographic variables are found to have a significant effect on usage of OTC analgesics. Females are predicted to use significantly more analgesics. A large proportion of the gender difference evaporates when controlling for various other determinants. Conclusion: A considerable part of the observed gender difference in OTC analgesic usage can be traced back to differences in frequency and severity of physical and mental health problems. Part of the gender difference in usage, however remains unexplained.展开更多
Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors.Recent studies have indicated the superiority of gait analysis over traditional evaluations(e.g., skin sensitivit...Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors.Recent studies have indicated the superiority of gait analysis over traditional evaluations(e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here,pain-related gait parameters, whose criteria include(1)alteration in pain models,(2) correlation with nociceptive threshold, and(3) normalization by analgesics, were identified in representative models of neuropathic pain(spared nerve injury: coordination data) and inflammatory pain(intraplantar complete Freund’s adjuvant: both coordination and intensity data) in the DigiGait^TM and CatWalk^TM systems. DigiGait^TM had advantages in fixed speed(controlled by treadmill) and dynamic SFI, while CatWalk^TM excelled in intrinsic velocity, intensity data,and high-quality 3 D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.展开更多
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 sour...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.展开更多
Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis.Using a molecular networking approach,five pairs of potent analgesic alkaloid enantiome...Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis.Using a molecular networking approach,five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of Anacyclus pyrethrum(A.pyrethrum).Their structures were elucidated by comprehensive spectroscopic data analysis,including LR-HSQMBC and 1H–15N HMBC,quantum 13C NMR DP4+and ECD calculations,and single-crystal X-ray diffraction analysis.Anacyphrethines A(1)and B(2)are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.11,23.04,28.05,17.09,16.011,15.021,27]nonacosane motif.Their biosynthetic pathways are proposed involving key aldol,hydroamination,and Schiff base reactions.All isolates showed potent analgesic effects in vivo.Even at a lower dose of 0.2 mg/kg,(±)-1 and(+)-1 still exhibited more potent analgesic activities than morphine.Interestingly,the racemic mixture(±)-1 showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg;while,(±)-1 showed significant analgesic activities comparable to(+)-1 at lower doses of 0.2 and 0.04 mg/kg.(+)-1 had stronger analgesic effect than(−)-1 at five tested does.Further tests on 44 analgesic-related targets demonstrated that(+)-1 showed significant inhibitory effects against many ion channels such as TRPM8,Kv1.2,Kv1.3,and Cav2.1 with IC50 values of 1.10±0.26,4.20±0.07,2.20±0.24,and 10.40±0.69μmol/L,respectively,while(−)-1 primarily inhibited TRPC6,Kv1.2,and Kv1.3 ion channels with IC50 values of 0.81±0.05,0.91±0.04,and 1.50±0.13μmol/L,respectively,without affecting the opioid receptors,suggesting their non-opioid analgesic potentials.The molecular dockings provided structural guidance to develop potent non-opioid analgesics.展开更多
Main observation and conclusion Fifteen 5,9-epoxygrayanane diterpenoids(1-15)including fourteen new ones,epoxymicranthols A-N(1-14),were isolated from the leaves extract of Rhododendron micranthum.Their structures wer...Main observation and conclusion Fifteen 5,9-epoxygrayanane diterpenoids(1-15)including fourteen new ones,epoxymicranthols A-N(1-14),were isolated from the leaves extract of Rhododendron micranthum.Their structures were elucidated via extensive spectroscopic methods and ^(13)C NMR-DP4+analysis,and the absolute configurations of 1,3-10,14,and 15 were confirmed by single-crystal X-ray diffraction analysis.展开更多
Objective： To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe （NUR） combined with opioid analgesics in managing cancer pain. Methods： All the patients enrolled were differentia...Objective： To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe （NUR） combined with opioid analgesics in managing cancer pain. Methods： All the patients enrolled were differentiated as of yin deficiency and meridian blocked syndrome type of TCM. Forty-one of them in the treated group were treated with NUR combined with opioid analgesics, while 43 of them in the control group were given opioid analgesics alone with successive 14 days as one treatment course for both groups. Results： The indexes of the treated group were superior to those in the control group as to the degree of pain-relieving, the therapeutic effect of analgesia, the occurrence frequency of cancer pain every day and its duration each time, the analgesic initial time, and the quality of life. Conclusion： NUR combined with opioid analgesics in cancer pain management was more effective than opioid analgesics alone. KEY WORDS展开更多
OBJECTIVE:To examine the effect of electroacupuncture(EA)application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery.METHODS:In this prospective,randomiz...OBJECTIVE:To examine the effect of electroacupuncture(EA)application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery.METHODS:In this prospective,randomized and controlled study,patients planned for periodontal surgery were divided into two groups[EA group(n=22):patients who received electroacupuncture and control group(n=22):patients who did not receive electroacupuncture].Electroacupuncture was applied bilaterally to the Hegu(LI4),Daying(ST5),and Jiache(ST5)points of the patients in the EA group immediately before and after the flap surgery for 30 min at a frequency of 50 Hz to each point at a current that the patient could tolerate.The patients in the control group underwent flap surgery without applying electroacupuncture.Patients were asked to record their pain levels on the visual analog scale and the number of analgesic tablets they took during the 7 postoperative days on the given form.RESULTS:The total mean score of pain felt in the EA group(16.60±2.78)was found to be significantly lower than that in the control group(31.37±2.78)(P=0.001).No significant difference was found between the groups regarding the amount of analgesics taken(4.77±4.72,5.82±3.11)(P=0.111).CONCLUSIONS:Our study shows that electroacupuncture application is beneficial in reducing pain after periodontal flap surgery.Overall,more research is needed to fully understand the effects of electroacupuncture on postoperative pain.展开更多
OBJECTIVE:to investigate the anti-arthritic effects of lappaconitine(LA)on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 ...OBJECTIVE:to investigate the anti-arthritic effects of lappaconitine(LA)on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 receptor(P2X7r).METHODS:Rats were immunized with complete Freund's adjuvant and then intraperitoneally administered LA(2,4,or 8 mg·kg^(-1)·d^(-1))or methotrexate(0.5 mg/kg per 3 d)for 14 d.The anti-arthritic effects of LA were evaluated through arthritis index(AI)assessment,ankle diameter measurement,and histopathological staining analysis.The analgesic effect of LA on arthritis was measured using mechanical withdrawal threshold testing and gait scoring.The impacts of LA on macrophage polarization,the expression of pro-/anti-inflammatory cytokines and P2X7r were analyzed using quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay,and Western blotting.RESULTS:LA treatment significantly reduced AI scores,paw swelling,joint destruction,and inflammatory cell infiltration,and alleviated arthritis pain.Additionally,LA promoted a balanced M1/M2 ratio by increasing the m RNA expression level of M2 marker arginase 1 and decreasing those of M1 markers inducible nitric oxide synthase and interleukin(IL)-1βin synovial tissues.Furthermore,LA lowered the levels of three M1-related cytokines,namely tumor necrosis factor-α,IL-1βand IL-18,and raised the level of the M2-related cytokine IL-10.Further research showed that treatment with LA inhibited the expression of P2X7r.CONCLUSION:Our findings indicate that the notable therapeutic and analgesic effects of LA on AIA rats are exerted through balancing the M1/M2 ratio,probably via P2X7r.展开更多
Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesi...Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.展开更多
[Objectives]To investigate the impact of the compatibility of Bombax malabaricum flowers and Osmanthus fragrans on the analgesic therapeutic effects in mice.[Methods]The analgesic effects of B.malabaricum flowers and ...[Objectives]To investigate the impact of the compatibility of Bombax malabaricum flowers and Osmanthus fragrans on the analgesic therapeutic effects in mice.[Methods]The analgesic effects of B.malabaricum flowers and O.fragrans,as well as their compatibility at a 1:1 ratio,were investigated using the hot plate test and the acetic acid writhing test.Observations were made regarding the reactions of mice,specifically the licking of their forepaws and hindpaws,both prior to and following drug administration.The duration of these reactions was recorded,and the pain threshold of the mice was assessed following drug administration.Additionally,the frequency of writhing responses was documented following the injection of acetic acid into the abdominal cavity of the mice for 20 min.[Results]The pain thresholds observed in the positive control group,the B.malabaricum flowers group,the O.fragrans group,and the compatibility group were significantly elevated compared to those of the blank control group following 14 d of drug administration(P<0.05).This finding indicates that the positive control group,the B.malabaricum flowers group,the O.fragrans group,and the compatibility group of B.malabaricum flowers and O.fragrans at a 1:1 ratio exhibited analgesic efficacy in mice.Furthermore,the pain thresholds of the B.malabaricum flowers and O.fragrans groups were significantly lower than that of the compatibility group(P<0.05),suggesting that the compatibility group demonstrated a significantly superior analgesic effect compared to the B.malabaricum flowers group in mice.A statistically significant difference was observed in the frequency of writhing responses among the five experimental groups:the normal saline group,the positive control group,the B.malabaricum flowers group,the O.fragrans group,and the compatibility group(P=0.01<0.05).Post hoc analyses revealed that the frequency of writhing responses in the O.fragrans group was significantly lower than that observed in both the normal saline group and the compatibility group.Additionally,the frequency of writhing responses in the positive control group was significantly lower than that in the normal saline group.[Conclusions]B.malabaricum flowers and O.fragrans,as well as their compatibility at a 1:1 ratio,exhibits analgesic effects,with the analgesic effect being more pronounced in the compatibility group compared to the B.malabaricum flowers group or the O.fragrans group.展开更多
BACKGROUND Although opioids and non-steroidal anti-inflammatory drugs are commonly used as preemptive analgesics in total knee arthroplasty(TKA),their side effects are a major concern.Tapentadol,a synthetic opioid ana...BACKGROUND Although opioids and non-steroidal anti-inflammatory drugs are commonly used as preemptive analgesics in total knee arthroplasty(TKA),their side effects are a major concern.Tapentadol,a synthetic opioid analgesic,is noted for its higher potency,lower abuse potential,and better gastrointestinal tolerability compared to traditional opioids.However,its efficacy and safety as preemptive analgesia in TKA have not been evaluated.AIM To hypothesize that preemptive use of tapentadol significantly reduces postoperative pain and rescue analgesic consumption in TKA patients.Clinically,this may reduce opioid burden and improve recovery protocols.METHODS Ninety patients undergoing unilateral TKA were randomized to receive either tapentadol(single dose of 100 mg sustained-release,n=45)or a matched placebo 1 hour before surgery.Postoperative pain was assessed using the visual analog scale(VAS),and total pain reduction scores were recorded.Total rescue analgesic consumption and side effects were monitored for 24 hours.Blood samples were collected 6 hours postoperatively to measure plasma levels of cholecystokinin(CCK)(a potential biomarker of pain)and tapentadol using enzyme-linked immunosorbent assay and high-performance liquid chromatography,respectively.RESULTS The baseline characteristics of both groups were comparable.The 24-hour VAS scores,the primary outcome,were significantly lower in the tapentadol group median[interquartile range(IQR)][1.0(1.0-3.0)]compared to the placebo group[3.5(2.0-5.0)].Significant differences in VAS scores were observed at 4 hours,6 hours,and 12 hours postoperatively(P<0.05).Requests for rescue analgesia were significantly delayed in the tapentadol group(P=0.01),and the total dose of analgesics used was significantly lower[median(IQR):3(2-4)]compared to the placebo group[4.5(3-5),P=0.001].No major adverse events were observed in either group.Plasma tapentadol concentrations correlated well with pain intensity,whereas no correlation was found between CCK levels and pain intensity.CONCLUSION A preemptive single dose of 100 mg oral tapentadol is safe,effective,and significantly reduces postoperative pain and rescue analgesic requirements in TKA patients.This approach may reduce opioid dependence and support enhanced recovery protocols.展开更多
BACKGROUND Esophageal cancer constitutes one of the most aggressive malignant neoplasms associated with poor clinical outcomes.While surgical resection remains the cornerstone of curative intervention,optimization of ...BACKGROUND Esophageal cancer constitutes one of the most aggressive malignant neoplasms associated with poor clinical outcomes.While surgical resection remains the cornerstone of curative intervention,optimization of perioperative care protocols has emerged as an essential strategy to reduce postoperative complications and potentially improve long-term survival rates in patients undergoing esophagectomy.However,substantial debate persists regarding the relative importance of various perioperative risk factors and their impact on post-resection outcomes.AIM To identify perioperative factors affecting prognosis after radical esophagectomy,aiming to improve patient outcomes through targeted interventions.METHODS A retrospective study analyzed 378 patients with esophageal cancer who underwent radical esophagectomy(McKeown,Sweet,or Ivor-Lewis procedures)from January 2022 through December 2023.All operations were performed by experienced surgeons following standardized perioperative protocols.The investigation gathered data on patient demographics,surgical parameters,tumor pathology(using the 8th edition American Joint Committee on Cancer staging system),and survival outcomes.Statistical analyses utilized Kaplan-Meier estimates and Cox proportional hazards modeling,with adjustment for confounding variables.RESULTS Multivariate Cox proportional hazards analysis identified three independent predictors of survival:Tumor-nodemetastasis staging[Hazard ratio(HR)=2.31,95%confidence interval(CI):1.72-3.10,P<0.001],tumor differentiation(moderate:HR=1.46,95%CI:1.02-2.09,P=0.038;poor:HR=2.15,95%CI:1.47-3.14,P<0.001),and extended postoperative analgesic use(>5 days)(HR=1.43,95%CI:1.08-1.89,P=0.012).Kaplan-Meier analysis demonstrated significantly lower overall survival rates in patients requiring analgesics for>5 days compared to≤5 days(P=0.003),with consistent patterns observed for both opioid(P=0.019)and nonsteroidal anti-inflammatory drug use(P=0.028).The extended analgesic group exhibited a higher proportion of elderly patients(48.47%vs 35.57%,P=0.015),while other baseline characteristics and tumor features remained comparable between groups.CONCLUSION Tumor-node-metastasis staging,tumor differentiation,and duration of postoperative analgesic use independently predict survival following radical esophagectomy,underscoring the significance of optimal pain management protocols.展开更多
Objective To systematically evaluate the overall efficacy of external application of traditional Chinese medicine(EA-TCM)in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-...Objective To systematically evaluate the overall efficacy of external application of traditional Chinese medicine(EA-TCM)in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain(CIBP).Methods We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems.It included four Chinese databases[Chinese Biomedical Literature Database(SinoMed),China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(VIP)],six English databases(Scopus,Embase,Web of Science,PubMed,Cochrane Library,and OpenGrey),and two registration systems(Chinese Clinical Trial Registry and ClinicalTrials.gov).The timeframe for the literature search extended from the inception of each database to December 31,2023.Meta-analysis was performed using RevMan(v5.4.1),and the outcome indicators(pain relief rate,analgesic duration,quality of life,pain intensity,breakthrough pain frequency,and adverse reactions)were graded using GRADE profiler(v3.6).Results According to the established inclusion and exclusion criteria,a total of 43 studies was deemed eligible,involving 3142 participants with CIBP.The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone,the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate[risk ratio(RR)=1.32,95%confidence interval(CI):1.24 to 1.41,P<0.00001],analgesic duration[mean difference(MD)=1.33,95%CI:0.97 to 1.69,P<0.00001],and quality of life(MD=5.66,95%CI:4.88 to 6.44,P<0.00001).Furthermore,the combined therapy significantly reduced pain intensity(MD=-1.00,95%CI:-1.19 to-0.80,P<0.00001),breakthrough pain frequency(MD=-0.43,95%CI:-0.51 to-0.36,P<0.00001),and adverse reactions(RR=0.60,95%CI:0.53 to 0.68,P<0.00001)in CIBP patients.Based on the GRADE assessment,the level of evidence varied from low to moderate.Conclusion EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life.Additionally,the EA-TCM can effectively reduce the incidence of adverse reactions associated with threestep analgesic therapy.展开更多
To seek for peripheral mechanism of electroacupuncture (EA) analgesia, observed effects of EA on activity of IL 1 and IL 2 in spleem cell in adjuvant arthritic (AA) rats of inflammatory pain model. METHODS Injected Fr...To seek for peripheral mechanism of electroacupuncture (EA) analgesia, observed effects of EA on activity of IL 1 and IL 2 in spleem cell in adjuvant arthritic (AA) rats of inflammatory pain model. METHODS Injected Freund’s complete adjuvant into the right hind paw of rats to produce AA model, stimulated Xuanzhong and Kunlun points with EA, adpoted H3 TdR and MTT methods to detect activity of IL 1 and SIL 2. RESULTS EA may raise activity of IL 1 and IL 2 in spleen cell in AA rats while Eaamalgesia. CONCLUSION The peripheral action of EA amalgesia on inflammatory pain is related to rising of IL 1 amd IL 2 activity.展开更多
OBJECTIVE:To observe the curative effect of an acupoint application with a Dingqi analgesic patch on moderate to severe pain caused by liver cancer.METHODS:Forty patients with moderate to severe pain caused by liver c...OBJECTIVE:To observe the curative effect of an acupoint application with a Dingqi analgesic patch on moderate to severe pain caused by liver cancer.METHODS:Forty patients with moderate to severe pain caused by liver cancer were randomly divided intoatreatmentgroup(TG)andacontrolgroup(CG).Patients with moderate pain were given 100 mg qd of a sustainably released tablet of tramadol hydrochloride;patientswithseverepainweregiven4.2mg q3d of the fentanyl transdermal system.The ashi points Ganshu(BL 18),Danshu(BL 19) and Qimen(LR 14) were chosen for the acupoint application intervention.CG patients were given a sham patch and TG patients were given a Dingqi analgesic patch.A visual analogue scale(VAS) was used before treatment and after 1,3,6,9 and 12 days of treatment.The Karnofsky score was measured before treatment and after 12 days of treatment.Any main adverse reactions(e.g.nausea,constipation,dizziness and headache) were recorded after 6 and 12 days of treatment.Any skin side effects(i.e.skin irritation and allergic reactions) were recorded.RESULTS:The VAS in TG was significantly lower than that in CG after 3,6,9 and 12 days of treatment(P<0.05).There was no significant difference in the Karnofsky score before treatment and after 12 days of treatment between CG and TG.There were also no significant differences in the main adverse reactions or skin side effects after 6 and 12 days of treatment between CG andTG(P>0.05).CONCLUSION:The Dingqi analgesic patch can enhance the analgesic effect of tramadol and fentanyl.展开更多
基金supported by NIH grant DE022912supported by NIH grant NS074430
文摘Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select novel targets for which there is proof of clinical relevance, either genetically through heritable traits, or pharmacolog- ically. Such an approach by definition yields targets with high clinical validity. The biology of these targets can be elucidated in animal models before returning to the patients with a refined therapeutic. For optimal treatment, having biomarkers of drug action available is also a plus. Here we describe a case study in rational drug design： the use of controlled inhibition of peripheral tetrahydrobiopterin （BH4） synthesis to reduce abnormal chronic pain states without altering nociceptive-protective pain. Initially iden- tified in a population of patients with low back pain, the association between BH4 production and chronic pain has been confirmed in more than 12 independent cohorts, through a common haplotype （present in 25% of Cau- casians） of the rate-limiting enzyme for BH4 synthesis, GTP cyclohydrolase 1 （GCH1）. Genetic tools in mice have demonstrated that both injured sensory neurons and activated macrophages engage increased BH4 synthesis to cause chronic pain. GCH1 is an obligate enzyme for de novo BH4 production. Therefore, inhibiting GCH1 activity eliminates all BH4 production, affecting the synthesis of multiple neurotransmitters and signaling molecules and interfering with physiological function. In contrast, target- ing the last enzyme of the BH4 synthesis pathway, sepiapterin reductase （SPR）, allows reduction of patholog- ical BH4 production without completely blocking physio- logical BH4 synthesis. Systemic SPR inhibition in mice has not revealed any safety concerns to date, and available genetic and pharmacologic data suggest similar responses in humans. Finally, because it is present in vivo only when SPR is inhibited, sepiapterin serves as a reliable biomarker of target engagement, allowing potential quantification of drug efficacy. The emerging development of therapeutics that target BH4 synthesis to treat chronic pain illustrates the power of combining human and mouse genetics： human genetic studies for clinical selection of relevant targets, coupled with causality studies in mice, allowing the rational engineering of new analgesics.
文摘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.
文摘T<span style="font-family:Verdana;">his work, contain<span style="font-family:Verdana;">s<span style="font-family:Verdana;"> some new compounds from benzimidazole derivatives, which <span style="font-family:Verdana;">are <span style="font-family:Verdana;">synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting <span style="font-family:Verdana;">in <span style="font-family:Verdana;">2-Mercapto-benzimidazole which <span style="font-family:Verdana;">is <span style="font-family:Verdana;">treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chlo<span style="font-family:Verdana;">roacetates, 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<span style="font-family:Verdana;">.
文摘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.
基金supported by National Institutes of Health HD057632the Buoniconti Fundthe Walter G.Ross Distinguished Chair in Developmental Neuroscience(to VPL)
文摘Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.
文摘Introduction: Usage of over-the-counter (OTC) analgesic has increased among Norwegian adolescents since 2001. It has been noted that females tend to have a higher usage compared to males. In this paper we explore this gender difference. Data: Our dataset consists of 284,674 from Norwegian adolescents attending junior high school and high school between 2014 and 2017. Methods: The econometric approach consists of applying ordered logistic regressions with usage of OTC analgesics as the dependent variable and a dichotomous gender variable as the independent variable. Control variables include variables such as frequency of physical and mental health problems and other sociodemographic variables. Results: Gender, physical and mental health problems and various sociodemographic variables are found to have a significant effect on usage of OTC analgesics. Females are predicted to use significantly more analgesics. A large proportion of the gender difference evaporates when controlling for various other determinants. Conclusion: A considerable part of the observed gender difference in OTC analgesic usage can be traced back to differences in frequency and severity of physical and mental health problems. Part of the gender difference in usage, however remains unexplained.
基金grants from the National Natural Science Foundation of China(31720103908 and31530028)the National Key Technology Support Program of the Ministry of Science and Technology of China(2017YFA0701300)
文摘Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors.Recent studies have indicated the superiority of gait analysis over traditional evaluations(e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here,pain-related gait parameters, whose criteria include(1)alteration in pain models,(2) correlation with nociceptive threshold, and(3) normalization by analgesics, were identified in representative models of neuropathic pain(spared nerve injury: coordination data) and inflammatory pain(intraplantar complete Freund’s adjuvant: both coordination and intensity data) in the DigiGait^TM and CatWalk^TM systems. DigiGait^TM had advantages in fixed speed(controlled by treadmill) and dynamic SFI, while CatWalk^TM excelled in intrinsic velocity, intensity data,and high-quality 3 D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.
文摘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.
基金supported by the National Key R&D Program of China(2020YFE0205600)the Biological Resources Program,Chinese Academy of Sciences(KFJ-BRP-007-011,China)+2 种基金National Natural Science Foundation of China(22477034 and 22277034)Interdisciplinary Research Program of HUST(2023JCYJ037,China)International Cooperation Project of Hubei provincial key R&D plan(2023EHA040,China).
文摘Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis.Using a molecular networking approach,five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of Anacyclus pyrethrum(A.pyrethrum).Their structures were elucidated by comprehensive spectroscopic data analysis,including LR-HSQMBC and 1H–15N HMBC,quantum 13C NMR DP4+and ECD calculations,and single-crystal X-ray diffraction analysis.Anacyphrethines A(1)and B(2)are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.11,23.04,28.05,17.09,16.011,15.021,27]nonacosane motif.Their biosynthetic pathways are proposed involving key aldol,hydroamination,and Schiff base reactions.All isolates showed potent analgesic effects in vivo.Even at a lower dose of 0.2 mg/kg,(±)-1 and(+)-1 still exhibited more potent analgesic activities than morphine.Interestingly,the racemic mixture(±)-1 showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg;while,(±)-1 showed significant analgesic activities comparable to(+)-1 at lower doses of 0.2 and 0.04 mg/kg.(+)-1 had stronger analgesic effect than(−)-1 at five tested does.Further tests on 44 analgesic-related targets demonstrated that(+)-1 showed significant inhibitory effects against many ion channels such as TRPM8,Kv1.2,Kv1.3,and Cav2.1 with IC50 values of 1.10±0.26,4.20±0.07,2.20±0.24,and 10.40±0.69μmol/L,respectively,while(−)-1 primarily inhibited TRPC6,Kv1.2,and Kv1.3 ion channels with IC50 values of 0.81±0.05,0.91±0.04,and 1.50±0.13μmol/L,respectively,without affecting the opioid receptors,suggesting their non-opioid analgesic potentials.The molecular dockings provided structural guidance to develop potent non-opioid analgesics.
基金This work was financially supported by the National Natural Science Foundation of China(No.U1703109).
文摘Main observation and conclusion Fifteen 5,9-epoxygrayanane diterpenoids(1-15)including fourteen new ones,epoxymicranthols A-N(1-14),were isolated from the leaves extract of Rhododendron micranthum.Their structures were elucidated via extensive spectroscopic methods and ^(13)C NMR-DP4+analysis,and the absolute configurations of 1,3-10,14,and 15 were confirmed by single-crystal X-ray diffraction analysis.
文摘Objective： To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe （NUR） combined with opioid analgesics in managing cancer pain. Methods： All the patients enrolled were differentiated as of yin deficiency and meridian blocked syndrome type of TCM. Forty-one of them in the treated group were treated with NUR combined with opioid analgesics, while 43 of them in the control group were given opioid analgesics alone with successive 14 days as one treatment course for both groups. Results： The indexes of the treated group were superior to those in the control group as to the degree of pain-relieving, the therapeutic effect of analgesia, the occurrence frequency of cancer pain every day and its duration each time, the analgesic initial time, and the quality of life. Conclusion： NUR combined with opioid analgesics in cancer pain management was more effective than opioid analgesics alone. KEY WORDS
文摘OBJECTIVE:To examine the effect of electroacupuncture(EA)application on postoperative pain levels and the amount of analgesic use in patients who underwent periodontal flap surgery.METHODS:In this prospective,randomized and controlled study,patients planned for periodontal surgery were divided into two groups[EA group(n=22):patients who received electroacupuncture and control group(n=22):patients who did not receive electroacupuncture].Electroacupuncture was applied bilaterally to the Hegu(LI4),Daying(ST5),and Jiache(ST5)points of the patients in the EA group immediately before and after the flap surgery for 30 min at a frequency of 50 Hz to each point at a current that the patient could tolerate.The patients in the control group underwent flap surgery without applying electroacupuncture.Patients were asked to record their pain levels on the visual analog scale and the number of analgesic tablets they took during the 7 postoperative days on the given form.RESULTS:The total mean score of pain felt in the EA group(16.60±2.78)was found to be significantly lower than that in the control group(31.37±2.78)(P=0.001).No significant difference was found between the groups regarding the amount of analgesics taken(4.77±4.72,5.82±3.11)(P=0.111).CONCLUSIONS:Our study shows that electroacupuncture application is beneficial in reducing pain after periodontal flap surgery.Overall,more research is needed to fully understand the effects of electroacupuncture on postoperative pain.
文摘OBJECTIVE:to investigate the anti-arthritic effects of lappaconitine(LA)on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 receptor(P2X7r).METHODS:Rats were immunized with complete Freund's adjuvant and then intraperitoneally administered LA(2,4,or 8 mg·kg^(-1)·d^(-1))or methotrexate(0.5 mg/kg per 3 d)for 14 d.The anti-arthritic effects of LA were evaluated through arthritis index(AI)assessment,ankle diameter measurement,and histopathological staining analysis.The analgesic effect of LA on arthritis was measured using mechanical withdrawal threshold testing and gait scoring.The impacts of LA on macrophage polarization,the expression of pro-/anti-inflammatory cytokines and P2X7r were analyzed using quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay,and Western blotting.RESULTS:LA treatment significantly reduced AI scores,paw swelling,joint destruction,and inflammatory cell infiltration,and alleviated arthritis pain.Additionally,LA promoted a balanced M1/M2 ratio by increasing the m RNA expression level of M2 marker arginase 1 and decreasing those of M1 markers inducible nitric oxide synthase and interleukin(IL)-1βin synovial tissues.Furthermore,LA lowered the levels of three M1-related cytokines,namely tumor necrosis factor-α,IL-1βand IL-18,and raised the level of the M2-related cytokine IL-10.Further research showed that treatment with LA inhibited the expression of P2X7r.CONCLUSION:Our findings indicate that the notable therapeutic and analgesic effects of LA on AIA rats are exerted through balancing the M1/M2 ratio,probably via P2X7r.
基金funded by National Natural Science Foundation of China(No.12172092,82174488,and 82305416)Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function(No.21DZ2271800)+1 种基金Shanghai Municipal Science and Technology Commission(No.23YF1418300)Scientific Research Project on Traditional Chinese Medicine of Shanghai Municipal Health Commission—Youth Guidance Category(No.2022QN018).
文摘Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program of Guangxi Zhuang Autonomous Region(S202310599060).
文摘[Objectives]To investigate the impact of the compatibility of Bombax malabaricum flowers and Osmanthus fragrans on the analgesic therapeutic effects in mice.[Methods]The analgesic effects of B.malabaricum flowers and O.fragrans,as well as their compatibility at a 1:1 ratio,were investigated using the hot plate test and the acetic acid writhing test.Observations were made regarding the reactions of mice,specifically the licking of their forepaws and hindpaws,both prior to and following drug administration.The duration of these reactions was recorded,and the pain threshold of the mice was assessed following drug administration.Additionally,the frequency of writhing responses was documented following the injection of acetic acid into the abdominal cavity of the mice for 20 min.[Results]The pain thresholds observed in the positive control group,the B.malabaricum flowers group,the O.fragrans group,and the compatibility group were significantly elevated compared to those of the blank control group following 14 d of drug administration(P<0.05).This finding indicates that the positive control group,the B.malabaricum flowers group,the O.fragrans group,and the compatibility group of B.malabaricum flowers and O.fragrans at a 1:1 ratio exhibited analgesic efficacy in mice.Furthermore,the pain thresholds of the B.malabaricum flowers and O.fragrans groups were significantly lower than that of the compatibility group(P<0.05),suggesting that the compatibility group demonstrated a significantly superior analgesic effect compared to the B.malabaricum flowers group in mice.A statistically significant difference was observed in the frequency of writhing responses among the five experimental groups:the normal saline group,the positive control group,the B.malabaricum flowers group,the O.fragrans group,and the compatibility group(P=0.01<0.05).Post hoc analyses revealed that the frequency of writhing responses in the O.fragrans group was significantly lower than that observed in both the normal saline group and the compatibility group.Additionally,the frequency of writhing responses in the positive control group was significantly lower than that in the normal saline group.[Conclusions]B.malabaricum flowers and O.fragrans,as well as their compatibility at a 1:1 ratio,exhibits analgesic effects,with the analgesic effect being more pronounced in the compatibility group compared to the B.malabaricum flowers group or the O.fragrans group.
文摘BACKGROUND Although opioids and non-steroidal anti-inflammatory drugs are commonly used as preemptive analgesics in total knee arthroplasty(TKA),their side effects are a major concern.Tapentadol,a synthetic opioid analgesic,is noted for its higher potency,lower abuse potential,and better gastrointestinal tolerability compared to traditional opioids.However,its efficacy and safety as preemptive analgesia in TKA have not been evaluated.AIM To hypothesize that preemptive use of tapentadol significantly reduces postoperative pain and rescue analgesic consumption in TKA patients.Clinically,this may reduce opioid burden and improve recovery protocols.METHODS Ninety patients undergoing unilateral TKA were randomized to receive either tapentadol(single dose of 100 mg sustained-release,n=45)or a matched placebo 1 hour before surgery.Postoperative pain was assessed using the visual analog scale(VAS),and total pain reduction scores were recorded.Total rescue analgesic consumption and side effects were monitored for 24 hours.Blood samples were collected 6 hours postoperatively to measure plasma levels of cholecystokinin(CCK)(a potential biomarker of pain)and tapentadol using enzyme-linked immunosorbent assay and high-performance liquid chromatography,respectively.RESULTS The baseline characteristics of both groups were comparable.The 24-hour VAS scores,the primary outcome,were significantly lower in the tapentadol group median[interquartile range(IQR)][1.0(1.0-3.0)]compared to the placebo group[3.5(2.0-5.0)].Significant differences in VAS scores were observed at 4 hours,6 hours,and 12 hours postoperatively(P<0.05).Requests for rescue analgesia were significantly delayed in the tapentadol group(P=0.01),and the total dose of analgesics used was significantly lower[median(IQR):3(2-4)]compared to the placebo group[4.5(3-5),P=0.001].No major adverse events were observed in either group.Plasma tapentadol concentrations correlated well with pain intensity,whereas no correlation was found between CCK levels and pain intensity.CONCLUSION A preemptive single dose of 100 mg oral tapentadol is safe,effective,and significantly reduces postoperative pain and rescue analgesic requirements in TKA patients.This approach may reduce opioid dependence and support enhanced recovery protocols.
文摘BACKGROUND Esophageal cancer constitutes one of the most aggressive malignant neoplasms associated with poor clinical outcomes.While surgical resection remains the cornerstone of curative intervention,optimization of perioperative care protocols has emerged as an essential strategy to reduce postoperative complications and potentially improve long-term survival rates in patients undergoing esophagectomy.However,substantial debate persists regarding the relative importance of various perioperative risk factors and their impact on post-resection outcomes.AIM To identify perioperative factors affecting prognosis after radical esophagectomy,aiming to improve patient outcomes through targeted interventions.METHODS A retrospective study analyzed 378 patients with esophageal cancer who underwent radical esophagectomy(McKeown,Sweet,or Ivor-Lewis procedures)from January 2022 through December 2023.All operations were performed by experienced surgeons following standardized perioperative protocols.The investigation gathered data on patient demographics,surgical parameters,tumor pathology(using the 8th edition American Joint Committee on Cancer staging system),and survival outcomes.Statistical analyses utilized Kaplan-Meier estimates and Cox proportional hazards modeling,with adjustment for confounding variables.RESULTS Multivariate Cox proportional hazards analysis identified three independent predictors of survival:Tumor-nodemetastasis staging[Hazard ratio(HR)=2.31,95%confidence interval(CI):1.72-3.10,P<0.001],tumor differentiation(moderate:HR=1.46,95%CI:1.02-2.09,P=0.038;poor:HR=2.15,95%CI:1.47-3.14,P<0.001),and extended postoperative analgesic use(>5 days)(HR=1.43,95%CI:1.08-1.89,P=0.012).Kaplan-Meier analysis demonstrated significantly lower overall survival rates in patients requiring analgesics for>5 days compared to≤5 days(P=0.003),with consistent patterns observed for both opioid(P=0.019)and nonsteroidal anti-inflammatory drug use(P=0.028).The extended analgesic group exhibited a higher proportion of elderly patients(48.47%vs 35.57%,P=0.015),while other baseline characteristics and tumor features remained comparable between groups.CONCLUSION Tumor-node-metastasis staging,tumor differentiation,and duration of postoperative analgesic use independently predict survival following radical esophagectomy,underscoring the significance of optimal pain management protocols.
基金Provincial Key Research and Development Project of Hunan(2018SK2127)Hunan Province Traditional Chinese Medicine Research and Development Project(201946).
文摘Objective To systematically evaluate the overall efficacy of external application of traditional Chinese medicine(EA-TCM)in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain(CIBP).Methods We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems.It included four Chinese databases[Chinese Biomedical Literature Database(SinoMed),China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(VIP)],six English databases(Scopus,Embase,Web of Science,PubMed,Cochrane Library,and OpenGrey),and two registration systems(Chinese Clinical Trial Registry and ClinicalTrials.gov).The timeframe for the literature search extended from the inception of each database to December 31,2023.Meta-analysis was performed using RevMan(v5.4.1),and the outcome indicators(pain relief rate,analgesic duration,quality of life,pain intensity,breakthrough pain frequency,and adverse reactions)were graded using GRADE profiler(v3.6).Results According to the established inclusion and exclusion criteria,a total of 43 studies was deemed eligible,involving 3142 participants with CIBP.The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone,the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate[risk ratio(RR)=1.32,95%confidence interval(CI):1.24 to 1.41,P<0.00001],analgesic duration[mean difference(MD)=1.33,95%CI:0.97 to 1.69,P<0.00001],and quality of life(MD=5.66,95%CI:4.88 to 6.44,P<0.00001).Furthermore,the combined therapy significantly reduced pain intensity(MD=-1.00,95%CI:-1.19 to-0.80,P<0.00001),breakthrough pain frequency(MD=-0.43,95%CI:-0.51 to-0.36,P<0.00001),and adverse reactions(RR=0.60,95%CI:0.53 to 0.68,P<0.00001)in CIBP patients.Based on the GRADE assessment,the level of evidence varied from low to moderate.Conclusion EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life.Additionally,the EA-TCM can effectively reduce the incidence of adverse reactions associated with threestep analgesic therapy.
文摘To seek for peripheral mechanism of electroacupuncture (EA) analgesia, observed effects of EA on activity of IL 1 and IL 2 in spleem cell in adjuvant arthritic (AA) rats of inflammatory pain model. METHODS Injected Freund’s complete adjuvant into the right hind paw of rats to produce AA model, stimulated Xuanzhong and Kunlun points with EA, adpoted H3 TdR and MTT methods to detect activity of IL 1 and SIL 2. RESULTS EA may raise activity of IL 1 and IL 2 in spleen cell in AA rats while Eaamalgesia. CONCLUSION The peripheral action of EA amalgesia on inflammatory pain is related to rising of IL 1 amd IL 2 activity.
基金Supported by the Administration of Traditional Chinese Medicine of Guangdong Province,China (No. 2010431)
文摘OBJECTIVE:To observe the curative effect of an acupoint application with a Dingqi analgesic patch on moderate to severe pain caused by liver cancer.METHODS:Forty patients with moderate to severe pain caused by liver cancer were randomly divided intoatreatmentgroup(TG)andacontrolgroup(CG).Patients with moderate pain were given 100 mg qd of a sustainably released tablet of tramadol hydrochloride;patientswithseverepainweregiven4.2mg q3d of the fentanyl transdermal system.The ashi points Ganshu(BL 18),Danshu(BL 19) and Qimen(LR 14) were chosen for the acupoint application intervention.CG patients were given a sham patch and TG patients were given a Dingqi analgesic patch.A visual analogue scale(VAS) was used before treatment and after 1,3,6,9 and 12 days of treatment.The Karnofsky score was measured before treatment and after 12 days of treatment.Any main adverse reactions(e.g.nausea,constipation,dizziness and headache) were recorded after 6 and 12 days of treatment.Any skin side effects(i.e.skin irritation and allergic reactions) were recorded.RESULTS:The VAS in TG was significantly lower than that in CG after 3,6,9 and 12 days of treatment(P<0.05).There was no significant difference in the Karnofsky score before treatment and after 12 days of treatment between CG and TG.There were also no significant differences in the main adverse reactions or skin side effects after 6 and 12 days of treatment between CG andTG(P>0.05).CONCLUSION:The Dingqi analgesic patch can enhance the analgesic effect of tramadol and fentanyl.
