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
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><span style="font-family:Verdana;">his work, contain</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> some ...T</span><span style="font-family:Verdana;">his work, contain</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> some new compounds from benzimidazole derivatives, which </span><span style="font-family:Verdana;">are </span><span style="font-family:Verdana;">synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting </span><span style="font-family:Verdana;">in </span><span style="font-family:Verdana;">2-Mercapto-benzimidazole which </span><span style="font-family:Verdana;">is </span><span style="font-family:Verdana;">treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chlo</span><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><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
Pain in chronic pancreatitis(CP)is difficult to manage.Many patients suffer from inadequate pain relief,completely incapacitating them in their daily activities.Historically,despite their well-known adverse effects,op...Pain in chronic pancreatitis(CP)is difficult to manage.Many patients suffer from inadequate pain relief,completely incapacitating them in their daily activities.Historically,despite their well-known adverse effects,opioids have been the pillar of treatment regimens in painful CP.The management is now gradually evolving with a better understanding of the underlying pathophysiology of CP-related pain.Clinicians should follow a holistic approach to the management of CPassociated pain,which must involve lifestyle changes that are coupled with analgesic medications and other pain-relieving interventions.Furthermore,there is no easy cure for vanquishing CP-associated pain.Each patient must be evaluated on a case-by-case basis by a multidisciplinary team to decide which treatment option is best suited for that individual.展开更多
Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to...Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.展开更多
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
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
Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and mol...Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.展开更多
Objective:To observe the analgesic effect of combined spinal and epidural anesthesia on older patients undergoing hip fracture surgery.Method:One hundred and twenty elderly hip fracture surgery patients treated in our...Objective:To observe the analgesic effect of combined spinal and epidural anesthesia on older patients undergoing hip fracture surgery.Method:One hundred and twenty elderly hip fracture surgery patients treated in our hospital from January 2021 to December 2022 were selected and randomly divided into two groups,with 60 cases in the experimental group and 60 in the control group.The experimental group was given combined spinal-epidural anesthesia intervention measures,while the control group was given epidural anesthesia intervention measures.The analgesic effect,tumor necrosis factor-alpha(TNF-α),C-reactive protein(CRP)levels,and other observation indicators were analyzed after anesthesia intervention.Result:After the intervention,the analgesic effect and the evaluation results of the subjects in the experimental group were better than those in the control group(P<0.05);the obtained values of TNF-αand CRP levels in the experimental group were higher than those of the control group(P<0.05).Conclusion:The combined spinal-epidural anesthesia intervention demonstrated positive outcomes.The analgesic effect of patients during surgery and their inflammatory factor levels improved,which makes this intervention worthy of clinical application and promotion.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
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
Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal...Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal,due to the short-term action of employed analgesics and their poor adverse effect profile.Due to their regenerative and anti-inflammatory properties,mesenchymal stem cells(MSCs)have been extensively investigated as a potential therapy for OA,and numerous preclinical and clinical studies found a significant improvement in joint pathology and function,pain scores and/or quality of life after administration of MSCs.Only a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by MSCs.In this paper,we review the evidence reported in literature that support the analgesic action of MSCs in OA,and we summarize the potential mechanisms of these antinociceptive effects.展开更多
Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as ...Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as fever,inflammation,and pharyngalgia both in adults and children.However,the instruction manual does not specify the exact usage and dosage of AOL for children.In this article,we set 6 dosage ranges:0.2,0.5,0.7,0.9,1.1,1.4 mL/kg/d,according to its dosage for adults and the conversion method between adult and children dosage.And six animal models were used to evaluate the effectiveness of AOL in different doses.The results indicated that AOL could reduce the lung index,virus load,and expression of proinflammatory cytokines in the lung.AOL could improve pathological changes and prolong the survival time of mice infected by the Influenza A virus(H1N1)A/PR/8/34 strains at 0.5–0.9 mL/kg/d concentrations in different degrees.The four dose groups of 0.7–1.4 mL/kg/d could significantly inhibit the ear shell swelling caused by xylene and reduce the rabbit body temperature induced by lipopolysaccharide(P<0.01,P<0.05).All the five dosage groups of 0.2–1.1 mL/kg/d could inhibit the increase of peritoneal capillary permeability induced by glacial acetic acid(P<0.01).AOL at 0.7 and 0.9 mL/kg/d reduced the painful writhing times in young mice induced by glacial acetic(P<0.01).These results indicated that the optimal dose of AOL in antiviral,antipyretic,anti-inflammatory,and analgesic effects is 0.7 mL/kg/d.展开更多
BACKGROUND During anesthesia administration for cataract surgery,low pH of proparacaine may induce pain or complications such as corneal damage and poor wound healing,with the use of additional drops intraoperatively ...BACKGROUND During anesthesia administration for cataract surgery,low pH of proparacaine may induce pain or complications such as corneal damage and poor wound healing,with the use of additional drops intraoperatively increasing the risk of complications.Accordingly,there is a clinical need for adjuncts to local anesthesia needs to improve the efficiency of anesthesia and reduce the required amount of intraoperative proparacaine.AIM To identify a method of anesthesia for geriatric cataract phacoemulsification that provides more efficient analgesia and improves clinical efficacy.METHODS A total of 130 geriatric patients with cataracts who attended Hebei Eye Hospital from December 2020 to December 2022 were included in the present study.Patients were divided into the proparacaine surface anesthesia(SA)group(65 cases)and the compound acupuncture-medicine anesthesia group(CAMA group,65 cases).Patients in the CAMA group were provided acupuncture analgesia in addition to SA.Preoperative anxiety[Self-Rating Anxiety Scale(SAS)score and state anxiety inventory(SAI)score],intraoperative stress,vital signs,analgesia,and cooperation,as well as postoperative adverse events,were compared between groups.RESULTS More marked reductions in anxiety were observed among patients in the CAMA group,with corresponding reductions in SAS and SAI scores.During the operation,no change in the secretion of E,NE,or Cor group compared to the preoperative period was observed in the CAMA,which was markedly lower than that in the SA group.Heart rate,blood pressure,and respiratory rate were more stable intraoperatively in the CAMA group.In addition,the incidence of intraoperative pain and the number of additional doses of anesthesia required in the CAMA group were markedly lower than in the SA group.Accordingly,patients in the CAMA group were able to avoid eye movements and eyelid closing leading to greater cooperation with surgeons during surgery.Furthermore,marked reductions in intraoperative adverse effects were observed in the CAMA group,indicating greater overall safety.CONCLUSION Proparacaine SA combined with acupuncture as an analgesic provides improved analgesia with greater safety compared to surface anesthesia with proparacaine during geriatric cataract phacoemulsification.展开更多
[Objectives]Peptides was extracted from Haemadipsa hainana and its activity was studied.[Methods]Electric stimulation,water extraction and ultrasonic extraction were used to extract the peptides from H.hainana.Then th...[Objectives]Peptides was extracted from Haemadipsa hainana and its activity was studied.[Methods]Electric stimulation,water extraction and ultrasonic extraction were used to extract the peptides from H.hainana.Then the protein content and molecular weight distribution of H.hainana peptides were detected by the BCA method and SDS-PAGE method,respectively.The antithrombin activity and analgesic activity of the three peptide extracts of H.hainana were detected by Markwardt thrombin titration method and mouse hot plate experiment,respectively.[Results]There extraction methods of electric stimulation,water extraction and ultrasonic extraction were used to extract the peptide extract of H.hainana,and the yields were as follows:water extraction>electrical stimulation>ultrasonic extraction.The three peptide extracts from H.hainana had antithrombin activity,and the antithrombin activity was as follows:water extraction>ultrasonic extraction>electrical stimulation.Through the hot plate experiment in mice,it was verified that the three peptide extracts of H.hainana had analgesic activity,and the analgesic activity was water extraction>electric stimulation>ultrasonic extraction.The analgesic activity of high-dose(100 mg/kg)group of H.hainana obtained by water extraction was slightly weaker than that of tramadol.[Conclusions]This study confirmed that the peptide extract of H.hainana had certain antithrombin and analgesic activity,laying a foundation for the subsequent development and application of H.hainana.展开更多
[Objectives]To study the effect of Zhuang medicine Clerodendrum japonicum(Thunb.)Sweet on acute tonsillitis.[Methods]The antibacterial,antipyretic,anti-inflammatory and analgesic effects of the extract of Zhuang medic...[Objectives]To study the effect of Zhuang medicine Clerodendrum japonicum(Thunb.)Sweet on acute tonsillitis.[Methods]The antibacterial,antipyretic,anti-inflammatory and analgesic effects of the extract of Zhuang medicine C.japonicum(Thunb.)Sweet were observed.[Results]Zhuang medicine C.japonicum(Thunb.)Sweet showed a good inhibitory effect onα-hemolytic streptococcus,β-hemolytic streptococcs,Staphylococcus citreus,Staphylococcus epidermidis,Staphylococcus aureus,Pseudomonas aeruginosa,Proteus and Escherichia coli;it showed a good inhibitory effect on the infection of Staphylococcus aureus andβ-hemolytic streptococcs in vivo;it could significantly reduce the elevated body temperature of rabbits injected with the triple vaccine and significantly increase the pain threshold of thermally stimulated mice.[Conclusions]Zhuang Medicine C.japonicum(Thunb.)Sweet has positive significance in the treatment of acute tonsillitis instead of antibiotics.展开更多
Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepato...Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.展开更多
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.
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><span style="font-family:Verdana;">his work, contain</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> some new compounds from benzimidazole derivatives, which </span><span style="font-family:Verdana;">are </span><span style="font-family:Verdana;">synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting </span><span style="font-family:Verdana;">in </span><span style="font-family:Verdana;">2-Mercapto-benzimidazole which </span><span style="font-family:Verdana;">is </span><span style="font-family:Verdana;">treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chlo</span><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><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.
文摘Pain in chronic pancreatitis(CP)is difficult to manage.Many patients suffer from inadequate pain relief,completely incapacitating them in their daily activities.Historically,despite their well-known adverse effects,opioids have been the pillar of treatment regimens in painful CP.The management is now gradually evolving with a better understanding of the underlying pathophysiology of CP-related pain.Clinicians should follow a holistic approach to the management of CPassociated pain,which must involve lifestyle changes that are coupled with analgesic medications and other pain-relieving interventions.Furthermore,there is no easy cure for vanquishing CP-associated pain.Each patient must be evaluated on a case-by-case basis by a multidisciplinary team to decide which treatment option is best suited for that individual.
文摘Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.
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.
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.
基金Supported by Central Talent Training Project for the Reform and Development of Local Colleges and Universities(2020GSP16)Guidance Project of Key R&D Plan in Heilongjiang Province(GZ20220039).
文摘Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.
基金Weifang Municipal Science and Technology Bureau(Medical)Project“Effects and Mechanisms of Oxycodone and Alfentanil on IgFs in Mouse Ovarian Granulosa Cells”(2021YX035)。
文摘Objective:To observe the analgesic effect of combined spinal and epidural anesthesia on older patients undergoing hip fracture surgery.Method:One hundred and twenty elderly hip fracture surgery patients treated in our hospital from January 2021 to December 2022 were selected and randomly divided into two groups,with 60 cases in the experimental group and 60 in the control group.The experimental group was given combined spinal-epidural anesthesia intervention measures,while the control group was given epidural anesthesia intervention measures.The analgesic effect,tumor necrosis factor-alpha(TNF-α),C-reactive protein(CRP)levels,and other observation indicators were analyzed after anesthesia intervention.Result:After the intervention,the analgesic effect and the evaluation results of the subjects in the experimental group were better than those in the control group(P<0.05);the obtained values of TNF-αand CRP levels in the experimental group were higher than those of the control group(P<0.05).Conclusion:The combined spinal-epidural anesthesia intervention demonstrated positive outcomes.The analgesic effect of patients during surgery and their inflammatory factor levels improved,which makes this intervention worthy of clinical application and promotion.
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
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Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal,due to the short-term action of employed analgesics and their poor adverse effect profile.Due to their regenerative and anti-inflammatory properties,mesenchymal stem cells(MSCs)have been extensively investigated as a potential therapy for OA,and numerous preclinical and clinical studies found a significant improvement in joint pathology and function,pain scores and/or quality of life after administration of MSCs.Only a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by MSCs.In this paper,we review the evidence reported in literature that support the analgesic action of MSCs in OA,and we summarize the potential mechanisms of these antinociceptive effects.
基金support of ABSL-2 biosafety laboratory of the Institute of Chinese Materia Medica.National Natural Science Foundation of China(No.82104500)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021B015).
文摘Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as fever,inflammation,and pharyngalgia both in adults and children.However,the instruction manual does not specify the exact usage and dosage of AOL for children.In this article,we set 6 dosage ranges:0.2,0.5,0.7,0.9,1.1,1.4 mL/kg/d,according to its dosage for adults and the conversion method between adult and children dosage.And six animal models were used to evaluate the effectiveness of AOL in different doses.The results indicated that AOL could reduce the lung index,virus load,and expression of proinflammatory cytokines in the lung.AOL could improve pathological changes and prolong the survival time of mice infected by the Influenza A virus(H1N1)A/PR/8/34 strains at 0.5–0.9 mL/kg/d concentrations in different degrees.The four dose groups of 0.7–1.4 mL/kg/d could significantly inhibit the ear shell swelling caused by xylene and reduce the rabbit body temperature induced by lipopolysaccharide(P<0.01,P<0.05).All the five dosage groups of 0.2–1.1 mL/kg/d could inhibit the increase of peritoneal capillary permeability induced by glacial acetic acid(P<0.01).AOL at 0.7 and 0.9 mL/kg/d reduced the painful writhing times in young mice induced by glacial acetic(P<0.01).These results indicated that the optimal dose of AOL in antiviral,antipyretic,anti-inflammatory,and analgesic effects is 0.7 mL/kg/d.
基金2019 Hebei Provincial Medical Science Research Project Plan,No.20191053.
文摘BACKGROUND During anesthesia administration for cataract surgery,low pH of proparacaine may induce pain or complications such as corneal damage and poor wound healing,with the use of additional drops intraoperatively increasing the risk of complications.Accordingly,there is a clinical need for adjuncts to local anesthesia needs to improve the efficiency of anesthesia and reduce the required amount of intraoperative proparacaine.AIM To identify a method of anesthesia for geriatric cataract phacoemulsification that provides more efficient analgesia and improves clinical efficacy.METHODS A total of 130 geriatric patients with cataracts who attended Hebei Eye Hospital from December 2020 to December 2022 were included in the present study.Patients were divided into the proparacaine surface anesthesia(SA)group(65 cases)and the compound acupuncture-medicine anesthesia group(CAMA group,65 cases).Patients in the CAMA group were provided acupuncture analgesia in addition to SA.Preoperative anxiety[Self-Rating Anxiety Scale(SAS)score and state anxiety inventory(SAI)score],intraoperative stress,vital signs,analgesia,and cooperation,as well as postoperative adverse events,were compared between groups.RESULTS More marked reductions in anxiety were observed among patients in the CAMA group,with corresponding reductions in SAS and SAI scores.During the operation,no change in the secretion of E,NE,or Cor group compared to the preoperative period was observed in the CAMA,which was markedly lower than that in the SA group.Heart rate,blood pressure,and respiratory rate were more stable intraoperatively in the CAMA group.In addition,the incidence of intraoperative pain and the number of additional doses of anesthesia required in the CAMA group were markedly lower than in the SA group.Accordingly,patients in the CAMA group were able to avoid eye movements and eyelid closing leading to greater cooperation with surgeons during surgery.Furthermore,marked reductions in intraoperative adverse effects were observed in the CAMA group,indicating greater overall safety.CONCLUSION Proparacaine SA combined with acupuncture as an analgesic provides improved analgesia with greater safety compared to surface anesthesia with proparacaine during geriatric cataract phacoemulsification.
基金Supported by"2020 Hainan Provincial Higher Education Teaching Reform Research and Scientific Research"Project of The Education Department of Hainan Province(Hnky2020-76)Research Fund of Hainan Health Management College(2020ZR01)。
文摘[Objectives]Peptides was extracted from Haemadipsa hainana and its activity was studied.[Methods]Electric stimulation,water extraction and ultrasonic extraction were used to extract the peptides from H.hainana.Then the protein content and molecular weight distribution of H.hainana peptides were detected by the BCA method and SDS-PAGE method,respectively.The antithrombin activity and analgesic activity of the three peptide extracts of H.hainana were detected by Markwardt thrombin titration method and mouse hot plate experiment,respectively.[Results]There extraction methods of electric stimulation,water extraction and ultrasonic extraction were used to extract the peptide extract of H.hainana,and the yields were as follows:water extraction>electrical stimulation>ultrasonic extraction.The three peptide extracts from H.hainana had antithrombin activity,and the antithrombin activity was as follows:water extraction>ultrasonic extraction>electrical stimulation.Through the hot plate experiment in mice,it was verified that the three peptide extracts of H.hainana had analgesic activity,and the analgesic activity was water extraction>electric stimulation>ultrasonic extraction.The analgesic activity of high-dose(100 mg/kg)group of H.hainana obtained by water extraction was slightly weaker than that of tramadol.[Conclusions]This study confirmed that the peptide extract of H.hainana had certain antithrombin and analgesic activity,laying a foundation for the subsequent development and application of H.hainana.
基金Supported by Key R&D Projects of Guangxi Science and Technology Department(Guike AB21196057)Guangxi Traditional Chinese Medicine Multidisciplinary Innovation Team Project(GZKJ2309)+4 种基金Qingmiao Talent Cultivation Project of Guangxi International Zhuang Medicine Hospital(2022001)Zhuang Pharmacy,a Key Discipline of Traditional Chinese Medicine(Ethnic Pharmacy)in the"12^(th)Five-year"Plan of the State Administration of Traditional Chinese MedicineFunding Project of High-level Talent Cultivation and Innovation Team of Guangxi University of Traditional Chinese Medicine(2022A008)Guangxi Natural Science Foundation(2019GXNSFAA245090)Liangqing District Science and Technology Plan Project in 2022(202202)。
文摘[Objectives]To study the effect of Zhuang medicine Clerodendrum japonicum(Thunb.)Sweet on acute tonsillitis.[Methods]The antibacterial,antipyretic,anti-inflammatory and analgesic effects of the extract of Zhuang medicine C.japonicum(Thunb.)Sweet were observed.[Results]Zhuang medicine C.japonicum(Thunb.)Sweet showed a good inhibitory effect onα-hemolytic streptococcus,β-hemolytic streptococcs,Staphylococcus citreus,Staphylococcus epidermidis,Staphylococcus aureus,Pseudomonas aeruginosa,Proteus and Escherichia coli;it showed a good inhibitory effect on the infection of Staphylococcus aureus andβ-hemolytic streptococcs in vivo;it could significantly reduce the elevated body temperature of rabbits injected with the triple vaccine and significantly increase the pain threshold of thermally stimulated mice.[Conclusions]Zhuang Medicine C.japonicum(Thunb.)Sweet has positive significance in the treatment of acute tonsillitis instead of antibiotics.
文摘Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.
