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Effects of fentanyl and sucrose on pain in retinopathy examinations with pain scale,near-infrared spectroscopy,and ultrasonography:a randomized trial

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World Journal of Pediatrics 2023年第9期19卷 873-882页

作者： Nursu Kara Didem Arman Zeynep Seymen Adem Gül Serdar Cömert Department of Pediatrics Division of NeonatologyUniversity of Health Sciences Istanbul Research and Training HospitalIstanbulTurkey Department of Opthalmology University of Health Sciences Istanbul Research and Training HospitalIstanbulTurkey

Background This study aimed to compare the efficacy of intravenous,intranasal fentanyl and oral sucrose in reducing the pain response during retinopathy of prematurity examinations using premature infant pain profile(PIPP)scores.Method The study included 42 infants who underwent retinopathy screening examinations.The infants were divided into three groups:oral sucrose,intranasal fentanyl,and intravenous fentanyl.Vital signs(heart rate,arterial oxygen saturation,and mean arterial pressure)were recorded.The PIPP was used to determine pain severity.Cerebral oxygenation and middle cerebral artery blood flow were evaluated using near-infrared spectroscopy and Doppler ultrasonography,respectively.The data obtained were compared between groups.Results There was no significant difference between the three groups regarding postconceptional and postnatal ages or birth weights and weight at the time of examination.All babies had moderate pain during the examination.No correlation was observed between analgesia method and pain scores(P=0.159).In all three groups,heart rate and mean arterial pressure increased,whereas oxygen saturation decreased during the exam compared with pre-examination values.However,heart rate(HR),mean arterial pressure(MAP)and arterial oxygen saturation(sPO2)values did not differ between groups(HR,P=0.150;MAP,P=0.245;sPO2,P=0.140).The cerebral oxygenation(rSO2)values between the three groups were found to be similar[rSO2:P=0.545,P=0.247,P=0.803;fractional tissue oxygen extraction(FTOE):P=0.553,P=0.278].Regarding cerebral blood flow values,we also did not find any difference between the three groups[mean blood flow velocity(Vmean):P=0.569,P=0.975;maximum flow velocity(Vmax):P=0.820,P=0.997].Conclusions Intravenous and intranasal fentanyl and oral sucrose were not superior to each other in preventing pain during the examination for retinopathy of prematurity(ROP).Sucrose may be a good alternative for pain control during ROP examination.Our findings suggest that ROP exam may not affect cerebral oxygenatio

关键词： analgesia Cerebral blood flow Cerebral oxygenation Neonate Retinopathy of prematurity

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Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathy via modulation of brain-derived neurotrophic factor expression

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中医杂志:英文版 2023年第4期43卷 686-694页

作者： Dong-Wook Kang Jae-Gyun Choi Hee Ju Song Jaehyuk Kim Miae Lee Taehee Kim Suk-Yun Kang Yeonhee Ryu Hwa Seung Yoo Jin Sun Lee Jin Bong Park Sang Do Lee Hyun-Woo Kim Department of Physiology and Medical Science College of Medicine and Brain Research InstituteChungnam National UniversityDaejeon 35015Republic of Korea KM Fundamental Research Division Korea Institute of Oriental Medicine Daejeon 34054Republic of Korea East-West Cancer Center Dunsan Korean Medicine Hospital of Daejeon UniversityDaejeon 35234Republic of Korea Department of Surgery Chungnam National University HospitalDaejeon 35015Republic of Korea Laboratory of Veterinary Pharmacology College of Veterinary Medicine and Research Institute for Veterinary ScienceSeoul National University1 Gwanak-roGwanak-guSeoul 08826Republic of Korea

OBJECTIVE:Chemotherapeutic agents such as docetaxel(DTX)can trigger chemotherapy-induced peripheral neuropathy(CIPN),which is characterized by unbearable pain.This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation(LFMNS)on DTX-induced tactile hypersensitivity in mice.METHODS:To produce CIPN,DTX was administered intraperitoneally 4 times,once every 2 d,to male ICR mice.LFMNS was performed on the wrist area,and the pain response was measured using von Frey filaments on both hind paws.Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brainderived neurotrophic factor(BDNF).RESULTS:Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area.CONCLUSIONS:LFMNS might be an effective nonpharmaceutical option for treating patients suffering from CIPN via regulating the expression of peripheral and central BDNF.

关键词： analgesia brain-derived neurotrophic factor chemotherapy-induced peripheral neuropathy docetaxel nerve stimulation

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Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain

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Neuroscience Bulletin 2022年第4期38卷 403-416页

作者： Fu-Jun Zhai Song-Ping Han Tian-Jia Song Ran Huo Xing-Yu Lan Rong Zhang Ji-Sheng Han Neuroscience Research Institute Peking UniversityBeijing 100191China Department of Neurobiology School of Basic Medical SciencesPeking UniversityBeijing 100191China Key Laboratory for Neuroscience Ministry of EducationNational Health CommissionPeking UniversityBeijing 100191China Wuxi HANS Health Medical Technology Co. Ltd.Wuxi 214122China Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China

Spinal cord stimulation(SCS)-induced analgesia was characterized,and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats.The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20%and 80%motor thresholds.Various frequencies(2,15,50,100,10000 Hz,and 2/100 Hz dense-dispersed)of SCS were similarly effective.SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation.SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid.The analgesic effect of 2 Hz was abolished byμorκopioid receptor antagonist.The effect of 100 Hz was prevented by aκantagonist,and that of 10 kHz was blocked by any of theμ,δ,orκreceptor antagonists,suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

关键词： SCS analgesia Opioid receptors Methionine-Enkephalin Dynorphin Endorphins

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Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1377-1389页

作者： Fangyu Du Ruolin Cao Lu Chen Jianwen Sun Yajie Shi Yang Fu Bruce D.Hammock Zhonghui Zheng Zhongbo Liu Guoliang Chen Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education School of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center University of California DavisDavisCA 95616USA Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 2550S6China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Soluble epoxide hydrolase(sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding(88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor(±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

关键词： Soluble epoxide hydrolase analgesia Synthesis Neuropathic pain Inhibitor

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Analgesic Effects of Two Types of Spinal Manipulation in Acute Lumbar Radiculopathy Model Rats

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Chinese Journal of Integrative Medicine 2022年第6期28卷 518-523页

作者： HAN Lei ZHAO Ping HAN Xue WEI Jie WANG Fei LI Yi GUO Guang-jin Spine Center of Manipulative Orthopedics Air Force Medical CenterBeijing100142China Department of Bone and Joint Imaging Diagnosis Wangjing Hospital of China Academy of Chinese Medical SciencesBeijing100102China

Objective:To compare the analgesic effects of two types of spinal manipulation(SM)in acute lumbar radiculopathy(ALR)model rats induced by self-transplantation of autologous nucleus pulposus(ANP),and clarify the therapeutic mechanism.Methods:Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table(18 rats in each group),including a blank group with no interference,a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment,a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference,a sham manipulation(SMA)group with simulating physical rotation,as well as a mobilization(MOB)group with simulating low-velocity and variable-amplitudle rotation and a manipulation(MAN)group with simulating high-velocity and low-amplitude rotation.The interventions in SMA,MOB,and MAN groups started 1 day after modeling followed by another 5 treatments at days 3,5,8,10 and 12.Rats in the other3 groups did not receive any special intervention.Behavioral pain tests of 50%mechanical pain withdrawal threshold(50%PWT)and paw withdrawal latency(PWL)were conducted 1 day before operation followed by another 10 tests on days 1-7,10,12 and 14.Immunohistochemical expression of nitric oxide synthase(NOS)was investigated on days 5 and 12 after operation.Results:After 3 experimental SM interventions,50%PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7,and higher on days 10,12 and14 postoperatively(P<0.05 or P<0.01),while the same indices were significantly higher in the MOB group than MAN group on days 1-4(P<0.05 or P<0.01).The expression of NOS was lower in the MAN and MOB groups than SMA group on day 12 postoperatively(P<0.01).Conclusions:Both manipulation and mobilization produced better results than sham interference in relieving pain by reducing neuroinflammation possibly.At the early period,compared with manipulation,mobilization presented less sensitive response to pain until

关键词： spinal manipulation radiculopathy anti-inflammation analgesia

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A long-form α-neurotoxin from cobra venom produces potent opioid-independent analgesia

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Acta Pharmacologica Sinica 2006年第4期27卷 402-408页

作者： Bo-wenCHEN RongHAN PaulFREID LaurenceNRAYMOND Department of Pharmacology Soochow University School of MedicineSuzhou 215007China ReceptoPharm PlantationFlorida 33324USA

Aim:In light of the antinociceptive activity of the short-chain neurotoxin,cobrotoxin,and other acetylcholine antagonists,the antinociceptive activity andmechanisms of cobratoxin(CTX),a long-chain postsynaptic α-neurotoxin,wasinvestigated in rodent pain models.Methods:CTX was administered intraperito-neally(30,45,68 μg/kg),intra-cerebral ventricularly(4.5 μg/kg)or microinjectedinto periaqueductal gray(PAG;4.5 μg/kg).The antinociceptive action was testedusing the hot-plate and acetic acid writhing tests m mice and rats.The involve-ment of the cholinergic system and opioid system in CTX-induced analgesia wasexamined by pretreatment of animals with atropine(0.5 mg/kg,im;or 10 mg/kg,ip)or naloxone(1 and 5 mg/kg,ip).The effect of CTX on motor activity was testedusing the Animex test.Results:CTX exhibited a dose-dependent analgesic ac-tion in mice as determined by both the hot-plate and acetic acid writhing tests.The peak effect of analgesia was seen 3 h after administration.In the mouse aceticacid writhing test,the intra-cerebral ventricular administration of CTX at 4.5 μg/kg(1/12th of a systemic dose)produced marked analgesic effects.Microinjection ofCTX(4.5 μgkg)into the PAG region did not elicit an analgesic action in rats in thehot-plate test.Atropine at 0.5 mg/kg(im)and naloxone at 1 and 5 mg/kg(ip)bothfailed to block the analgesic effects of CTX,but atropine at 10 mg/kg(ip)didantagonize the analgesia mediated by CTX in the mouse acetic acid writhing test.Acetylsalicylic acid(300 mg/kg)did not enhance the analgesic effects of CTX.Atthe highest effective dose of 68 μg/kg the neurotoxin did not change the sponta-neous mobility of mice.Conclusion:CTX has analgesic effects,which are medi-ated in the central nervous system though not through the PAG.The centralcholinergic system but not opioid system appears to be involved in theantinociceptive action of CTX.

关键词： cobratoxin analgesia periaqueductal gray matter atropine naloxone

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Effect of wrist-ankle acupuncture on propofol dosage during painless colonoscopy:A randomized controlled prospective study

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World Journal of Clinical Cases 2022年第12期10卷 3764-3772页

作者： Tao He Chan Liu Zhi-Xia Lu Li-Li Kong Yan Li Zhe Xu Ya-Jing Dong Wei Hao Department of Anesthesiology Hebei Provincial Hospital of Traditional Chinese MedicineShijiazhuang 050000Hebei ProvinceChina Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research(Hebei) Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research(Hebei)Shijiazhuang 050000Hebei ProvinceChina

BACKGROUND The clinical advantages of painless colonoscopy can reduce the fear and discomfort of patients and increase the detection rate of diseases.Propofol has the characteristics of fast effect and short action time.It is a common choice for painless endoscopic sedation and anesthetics.However,propofol can cause severe respiratory and circulatory depression.Therefore,it is important to find a way to reduce the dose of propofol.AIM To explore the effect of wrist-ankle acupuncture on propofol dose during colonoscopy.METHODS Two hundred patients who were going to receive selective painless colonoscopy in Hebei Hospital of Traditional Chinese Medicine were selected and divided into wrist-ankle acupuncture group(WAA group,n=100)and control group(CON group,n=100).After entering the operation room,patients were given 0.025 mg/kg nabufine intravenously and propofol at the initial dose of 0.5 mg/kg.In patients who did not fall asleep,propofol(10 mg/time)was given until loss of consciousness.Prior to anesthesia,patients in WAA group were punctured by specialist in the inferior 1,2 and 3 regions according to the zoning principle of wrist-ankle acupuncture.The primary endpoint was required dose of propofol,and the secondary endpoints were the incidence of hypoxemia and hypotension.Furthermore,the following data were recorded:The operation time,wake-up time,incidence of nausea and vomiting,incidence of abdominal distention,post colonoscopy pain,examiners'satisfaction,patients'satisfaction and Borg fatigue index.This study has been registered in the Chinese Clinical Trial Registry(Registration Code:ChiCTR1900022177).RESULTS The induced dose of propofol and the total dose of propofol in WAA group were 80 mg and 110 mg,respectively,which were significantly lower than those in CON group(P<0.05).The incidences of hypoxemia and hypotension in the WAA group were 2.2%and 3.3%,respectively,significantly lower than those in the CON group(P<0.05).The incidence of abdominal distension in the WAA group was 8.8%,which was significantly

关键词： Wrist-ankle acupuncture Ankle Painless colonoscopy analgesia

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Impact of CYP3A4*1G Polymorphism on Fentanyl analgesia Assessed by analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy

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Chinese Medical Journal 2018年第22期131卷 2693-2698页

作者： Qi Yan Yi Su Lan Gao Nan Ding Hong-Ying Zhang Wen E Yue Wang Yi Feng Hai-Yan An Department of Anesthesiology Peking University People's HospitalBeijing 100044China Department of Anesthesiology Jincheng Maternal and Child Health Care HospitalJinchengShanxi 048000China Department of Pathology Peking University Health Science CenterBeijing 100191China Department of Gynecology Peking University People's HospitalBeijing 100044China

Background:The clinical efficacy of fentanyl for pain control differs greatly across individuals.The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1,GG),mutant heterozygote (CYP3A4*1/*1G,GA),and mutant homozygote (CYP3A4*1G/*1G,AA)on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI). Methods:A total of 200 gynecologic patients scheduled for elective hysteroscopy under general anesthesia at Peking University People's Hospital from May to December in 2017 were enrolled in this study.Venous blood was withdrawn for genotyping of CYP3A4*1G before operation.Fentanyl 1μg/kg was administered preoperatively followed by target-controlled infusion of propofol for induction and maintenance.Intraoperative analgesic efficacy of fentanyl was assessed by ANI monitoring at T0(entering room),T1(cervical dilation), T2(start of cervical aspiration),and T3(end of cervical aspiration)time points.The duration of propofol infusion and total dosage of propofol were recorded as well. Results:The patients were divided into three groups according to CYP3A4*1G polymorphism,including 143 in GG group,47in GA group, and 10 in AA group.There was no significant difference in clinical demographics among three groups.The frequency of CYP3A4*1G variant alleles accounted for 16.8%and the distribution of variant alleles was consistent with Hardy-Weinberg equilibrium.Using a multilevel model,ANI values at T1(63.81±19.61),T2(63.63±17.82),and T3(65.68±17.79)were significantly lower than that at T0 (77.16±12.93)in the study population (F =23.50,P <0.001),suggesting that higher levels of pain at T 1,T2,and T3 than T0.Patients with GG genotype showed significantly lower ANI than those with GA or AA genotypes during hysteroscopy under the same dose of fentanyl. Conclusion:CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesth

关键词： analgesia CYP3A4 Fentanyl Genetic Polymorphism

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A comparative study of three concentrations of intravenous nalbuphine combined with hydromorphone for post-cesarean delivery analgesia

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Chinese Medical Journal 2020年第5期133卷 523-529页

作者： Chun-Yun Huang Shu-Xi Li Mei-Juan Yang Li-Li Xu Xin-Zhong Chen Department of Anesthesia Women’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China

Background:Nalbuphine has been suggested to be used for post-cesarean section(CS)intravenous analgesia.However,ideal concentration of nalbuphine for such analgesia remains unclear.The present study was conducted to explore an ideal concentration of nalbuphine for post-CS intravenous analgesia by evaluating the analgesic effects and side-effects of three different concentrations of nalbuphine combined with hydromorphone for post-CS intravenous analgesia in healthy parturients.Methods:One-hundred-and-fourteen parturients undergoing elective CS were randomly allocated to one of three groups(38 subjects per group)according to an Excel-generated random number sheet to receive hydromorphone 0.05 mg/mL+nalbuphine 0.5 mg/mL(group LN),hydromorphone 0.05 mg/mL+nalbuphine 0.7 mg/mL(group MN),and hydromorphone 0.05 mg/mL+nalbuphine 0.9 mg/mL(group HN)using patient-controlled analgesia(PCA)pump.Visual analog scale(VAS)for pain,PCA bolus demands,cumulative PCA dose,satisfaction score,Ramsay score,and side-effects such as urinary retention were recorded.Results:The number of PCA bolus demands and cumulative PCA dose during the first 48 h after CS were significantly higher in group LN(21±16 bolus,129±25 mL)than those in group MN(15±10 bolus,120±16 mL)(both P0.05).VAS scores were significantly lower in group HN than those in group MN and group LN for uterine cramping pain at rest and after breast-feeding within 12 h after CS(all P0.05).Ramsay sedation scale score in groupHNwas significantly higher than that in group MN at 8 and 12 h after CS(all P<0.01)and group LN at 4,8,12,24 h after CS(all P<0.05).Conclusions:Hydromorphone 0.05 mg/mL+nalbuphine 0.7 mg/mL f

关键词： Hydromorphone Nalbuphine Cesarean section Post-operative analgesia Patient-controlled intravenous analgesia

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Optimum interval time of programmed intermittent epidural bolus of ropivacaine 0.08%with sufentanyl 0.3 mg/mL for labor analgesia:a biased-coin up-and-down sequential allocation trial

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Chinese Medical Journal 2020年第5期133卷 517-522页

作者： Shuang-Qiong Zhou Jing Wang Wei-Jia Du Yu-Jie Song Zhen-Dong Xu Zhi-Qiang Liu Department of Anesthesia Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China Department of Anesthesia Fujian Provincial Maternity and Children’s HospitalAffiliated Hospital of Fujian Medical UniversityFuzhouFujian 350001China

Background:The programmed intermittent epidural bolus(PIEB)technique is widely used in labor analgesia,but the parameter settings of PIEB have not yet been standardized.We designed a study to identify the optimal interval duration for PIEB using 10 mL of ropivacaine 0.08%and sufentanyl 0.3 mg/mL,a regimen commonly used to control labor pain in China,to provide effective analgesia in 90%of women during the first stage of labor without breakthrough pain.Methods:We conducted a double-blind sequential allocation trial to obtain the effective interval 90%(EI90%)during the first stage of labor between April 2019 and May 2019.This study included the American Society of Anesthesiologists physical status II–III nulliparous parturients at term,who requested epidural analgesia.The bolus volume was fixed at 10 mL of ropivacaine 0.08%with sufentanyl 0.3 mg/mL.Participants were divided into four groups(groups 60,50,40,and 30)according to the PIEB intervals(60,50,40,and 30 min,respectively).The interval duration of the first parturient was set at 60 min and that of subsequent parturients varied according to a biased-coin design.The truncated Dixon and Mood method and the isotonic regression analysis method were used to estimate the EI90%and its 95%confidence intervals(CIs).Results:Forty-four women were enrolled in this study.The estimated optimal interval was 44.1 min(95%CI 41.7–46.5 min)and 39.5 min(95%CI 32.5–50.0 min),using the truncated Dixon and Mood method and isotonic regression analysis,respectively.The maximum sensory block level above T6 was in nearly 20%of parturients in group 30;however,5.3%,0%,and 0%of the parturients presented with sensory block level above T6 in groups 40,50,and 60,respectively.There were no cases of hypotension and only one parturient complained of motor block.Conclusion:With a fixed 10 mL dose of ropivacaine 0.08%with sufentanyl 0.3 mg/mL,the optimal PIEB interval is about 42 min.Further studies are warranted to define the efficacy of this regimen throughout all stages of labor.

关键词： Anaesthetic techniques First stage labor Labor analgesia Ropivacaine

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