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Objective:To evaluate the role of spinal ninjurin 2 (NINJ2) in the neuropathic pain (NP) and the relationship with nuclear factor kappa B (NF-κB) signaling pathway in rats.Methods:Thirty-two clean-grade healthy male Sprague-Dawley rats, weighing 230-260 g, aged 7-8 weeks, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), NP group, NP plus NINJ2 interfering virus group (NP+ siRNA group) and NP plus control virus group (NP+ scrRNA group). After intrathecal catheterization, rats in sham group and NP group received normal saline 10 μl, while NP+ NINJ2 siRNA group and NP+ scrRNA group received NINJ2 siRNA 10 μl and scrRNA 10 μl, respectively.NP model was developed via ligation of tibial nerve and common peroneal nerve one week later.Sham group only exposed the sciatic nerve and its branches.The mechanical paw withdrawal threshold (MWT) on the operated side was measured on preoperative days 3 and 1 and postoperative days 1, 3, 5, 7, 10 and 14.The rats were sacrificed at postoperative day 14, and the lumbar enlargement segments of the spinal cord were harvested for determination of the expression of NINJ2 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with Sham group, the MWT on the operated side was significantly decreased, the expression of NINJ2 and p-NF-κB p65 in spinal cord was up-regulated, and contents of TNF-α, IL-1β and IL-6 were increased on the postoperative days 3, 5, 7, 10 and 14 in the other three groups ( P<0.05). Compared with NP group, the MWT on the operated side was significantly increased, the expression of NINJ2 and p-NF-κB p65 in spinal cord was down-regulated, and contents of TNF-α, IL-1β and IL-6 were decreased on the postoperative days 3, 5, 7, 10 and 14 in NP+ siRNA group ( P<0.05), and no significant change was found in each parameter mentioned above at different time points in NP+ scrRNA group ( P>0.05). Conclusion:NINJ2 is involved in NP, which is related to activation of NF-κB signaling pathway in rats.
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Objective To evaluate the effect of CYP3A4*1G genetic polymorphism on the pharmacokinetics of levobupivacaine after epidural administration.Methods One hundred and eleven American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 30-60 yr,weighing 56-79 kg,scheduled for elective lower extremity surgery under epidural anesthesia,were enrolled in the study.Blood sampies were collected from the central vein before anesthesia for detection of CYP3A4*1G genotypes by polymerase chain reaction-restriction fragment length polymorphism.The patients were divided into 3 groups according to the CYP3A4*1G genotypes:wild hemozygote (CYP3A4*1/*1) group (w/w group),mutation heterozygote (CYP3A4*1/*1G) group (m/w group) and mutation hemozygote (CYP3A4*1G/*1G) group (m/m group).An epidural catheter was placed at the L1,2 interspace,and 0.75％ levobupivacaine 1.8 mg/kg was injected.Thirty-four patients were randomly selected,and blood samples from the central vein were collected at0,10,20,30,45,60,90,120,180,240,360,480,840 and 1 440 min after administration for determination of plasma concentrations of levobupivacaine by high-performance liquid chromatography.The pharmacokinetic parameters were calculated.Results There were 42 cases in group w/w,59 cases in group m/w,and 10 cases in group m/m.The frequency of CYP3A4*1G variant allele was 35.6％ in the 111 patients underwent lower extremity surgery.There were no significant differences between the three groups in the plasma concentrations of levobupivacaine at different time points,elimination halflife,clearance,distribution volume,elimination rate constant,peak plasma concentration,time to peak plasma concentration or area under the concentration-time curve (P＞0.05).Conclusion CYP3A4*1G genetic polymorphism is not one of the genetic factors contributing to the individual variation in the pharmacokinetics of levobupivacaine after epidural administration.
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Objective To evaluate the effect of resolvin D1 on focal cerebral ischemia?reperfusion ( I∕R) injury in rats. Methods One hundred and twenty adult male Sprague?Dawley rats, aged 7 weeks, weighing 260-280 g, were randomly divided into 5 groups ( n=24 each) using a random number table:sham operation group (group S), group I∕R, low?dose resolvin D1 group (group LRD), medium?dose resolvin D1 group ( group MRD) , and high?dose resolvin D1 group ( group HRD) . Focal cerebral I∕R was induced by right middle cerebral artery occlusion using a nylon thread inserted into internal carotid artery and advanced cranially until resistance was met. The occlusion was maintained for 2 h followed by 24 h reperfusion. In LRD, MRD and HRD groups, 0.03, 0.10, 0.30 nmol resolvin D1 5 μl was injected into the lateral cerebral ventricle at the beginning of reperfusion, respectively. Neurological deficits were evaluated at 24 h of reperfusion and scored. The rats were then sacrificed, and their brains were removed for determination of infarct volume (by TTC staining), cerebral water content, Evans blue content and expression of matrix metalloproteinase?9 ( MMP?9) in the ischemic cortex. Results Compared with group S, the neurological deficit scores, cerebral infarct volume, and cerebral water and Evans blue content were significantly increased, and the expression of MMP?9 was up?regulated in the other 4 groups. Compared with group I∕R, the neurological deficit scores, cerebral infarct volume, and cerebral water and Evans blue content were significantly decreased, and the expression of MMP?9 was down?regulated in group MRD and group HRD, and no significant change was found in the parameters mentioned above in group LRD. Conclusion Resolvin D1 can attenuate focal cerebral I∕R injury in rats, and down?regulation of MMP?9 expression and decrease in permeability of blood?brain barrier may be involved in the mechanism.
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Objective To evaluate the effects of gender on the pharmacokinetics of propofol in patients.Methods Twenty ASA physical status Ⅰ or Ⅱ patients of both sexes (10 male,10 female),aged 42-59 yr,weighing 46-76 kg,scheduled for elective surgery for gastrointestinal cancer,were randomly divided into 2 gender groups (n =10 each):male group and female group.Combined intravenous-inhalational anesthesia was performed during surgery.Anesthesia was induced with iv injection of 2％ propofol 2 mg/kg,remifentanil 1.5 μg/kg,and suxamethonium chloride 1.5 mg/kg.The patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with inhalation of the mixture of 1％-2 ％ isoflurane and nitrous oxide (N2 O ∶ O2 =1 ∶ 1.),iv infusion of remifentanil 0.2-0.3 μg/kg and intermittent iv boluses of atracurium.Blood samples were taken from the central vein before propofol administration,and at 1,2,3,4,6,10,15,30,45,60,90,120,180,240,360 and 720 min after propofol administration for determination of the plasma concentration of propofol by high-performance liquid chromatography.The blood concentration-time curve of propofol was drawn and the pharmacokinetic parameters were calculated.Results The blood concentrations of propofol were significantly lower at each time points within 10 rmin after administration of the single bolus of propofol in female group than in male group (P ＜0.05).The blood concentration-time curves of propofol were fitted to a three-compartment open model in the 2 groups.The central volume of distribution and clearance rate were significantly larger in female patients than in male patients (P ＜ 0.05).Conclusion After iv injection of propofol,the blood concentration of propofol is lower,and the central volume of distribution and clearance rate are larger in female than in male,suggesting that gender has significant effect on pharmacokinetics of propofol.
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ObjectiveTo evaluate the feasibility of using dexmedetomidine (Dex) as supplement to stellate ganglion block (SGB) in the treatment of trigcminal post-herpetic neuralgia in elderly patients.MethodsForty-five ASA Ⅱ patients with trigeminal post-herpetic neuralgia aged 65-85 yr weighing 45-85 kg undergoing stellate ganglion block were randomly divided into 3 groups ( n =15 each): group SGB; group Dex 0.4 and 0.6 μg/kg +SGB (groups DS1 and DS2).SGB was performed on the affected side with 0.5％ ropivacaine 8-10 ml.Dex 0.4 and 0.6 μg/kg in normal saline were infused iv over 15 min before SGB in groups DS1 and DS2 respectively.The onset time and duration of block were recorded.Bradycardia,hypotension and respiratory depression were also recorded.The intensity of pain was assessed with VAS scores (0=no pain,10 =worst pain) before and at 1,2,4,8 weeks after SGB.VAS score ≤3 was defined as satisfactory analgesia.The rate of satisfactory analgesia was calculated.ResultsThere was no significant difference in the incidence of bradycardia,hypotension and respiratory depression among the 3 groups.The duration of block was significantly longer and the rate of satisfactory analgesia at 2,4,8 weeks after SGB was significantly higher in groups DS1 and DS2 than in group SGB.There was no significant difference in the onset time,duration of block and the rate of satisfactory analgesia between groups DS1 and DS2.ConclusionSGB with Dex has better therapeutic effect than SGB in elderly patients with trigeminal post-herpetic neuralgia.
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Objective To investigate the pharmacokinetics of different concentrations of levobupivacaine for lumbar epidural anesthesia.Methods Twenty ASA Ⅰ or Ⅱ patients of both sexes, aged 35-59 years and scheduled for elective radical resection of rectal or colon carcinoma under general anesthesia combined with epidural block, were randomly divided into 2 groups (n=10 each):group Ⅰ (receiving 0.75% levobupivacaine) and group Ⅱ (receiving 0.5% levobupivacaine). Epidural block was performed at L1-2 interspace. Group Ⅰ and Ⅱ received epidural 0.75% and 0.5% levobupivacaine 2 mg/kg (containing adrenaline 5 μg/kg)injected slowly over 2 min, respectively. And 30 min later, general anesthesia was induced with y-hydroxybutyrate 60-80 mg/kg and remifentanil 1-2μg/kg. Tracheal intubation was facilitated with succinylcholine 1-1.5 mg/kg and the patients were mechanically ventilated. Anesthesia was maintained with inhalation of nitrous oxide (N2 O) and O2 (1:1) and continuous infusion of remifentanil 0.01-0.1μg·kg-1·min-1 and intermittent intravenous boluses of atracurium. Sensory and motor blocks were assessed after epidural levobupivacaine. Blood samples were taken from the central vein at 0, 10, 20, 30, 45, 60, 90, 120, 210, 300, 420,540, 660 and 840 min, respectively, after epidural administration for determination of plasma concentrations of levobupivacaine by high performance liquid chromatography.Results The plasma concentration-time curves of levobupivacaine were fitted to a two-compartment open model in the two groups and there were no significant differences in the pharmacokinetic profiles between the two groups. The onset time of sensory and motor blocks was shorter and the duration of the two blocks was longer with 0.75% levobupivacaine as compared with 0.5%levobupivacaine. The incidences of nausea and vomiting and hypotension were low and no severe cardiovascular and neurological side-effects developed.Conclusion The pharmacokinetic parameters do not differ significantly between epidural 0.75% and 0.5% levobupivacaine when the total doses are the same. And epidural anesthesia with either 0.75% or 0.5% levobupivacaine is safe.
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Objective To investigate the effects of age on the pharmacokineties and pharmacodynamics of levobupivacaine after epidural administrstion.Methods Forty-five ASA Ⅰ or Ⅱ patients of both sexes (26 male, 19 female) aged 30-72 yr, weighing 52-83 kg scheduled for elective lower extremity surgery under epidural anesthesia, were divided into 3 age groups ( n = 15 each) : group Ⅰ≤45 yr; group Ⅱ 46-64 yr and group Ⅲ > 64 yr. Epidural anesthesia was performed at the L1,2 interspace. All of the patients received levobupivacaine 1.8 mg/kg with epinephrine 5 μg/ml given epidurally over 1.5 min. Assessment of sensory block (onset time, peak effect time, upper spread of sensory block, duration of anesthesia) and degree of motor block (using modified Bromage scale) were made. Blood samples were taken from central vein at 0, 10, 20, 30, 45, 60 90, 120, 240, 360, 480, 840 and 1 440 min after epidural administration for determination of plasma concentration of levobupivacaine by high-performance liquid chromatography (HPLG) in nine patients in each group. The pharmacokinetic parameters were calculated from plasma concentration-time data with 3P97 software package. Results The cephalad spread of sensory block was significantly higher in group Ⅲ than in group Ⅰ . The duration of sensory and motor block was significantly longer in group Ⅲ than in group Ⅰ . The plasma concentration-time curves of levobupivacaine were fitted to a two-compartment open model in the 3 groups. The plasma concentrations of levobupivacaine were significantly higher at 1 440 min after epidural administration in group Ⅲ and Ⅱ than in group Ⅰ. The t1/2β was significantly different among the 3 groups. Conclusion 0.75% levobupivacaine is safe and effective for epidural anesthesia. Age affects the pharmacokinetics (t1/2β in particular) and pharmacodynamics of levobupivacaine administered epidurally.
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Objective To investigate the pharmacokinetics of epidural ropivacaine in patients with liver dysfunction.Methods Twenty patients aged 20-58 yrs weighing 45-73 kg scheduled for upper abdominal surgery under general combined with epidural anesthesia were divided into 2 groups (n = 10 each) : group Ⅰ patients with obstructive jaundice and group Ⅱ patients with normal liver function. Epidural block was performed at T8.9 interspace. 0.75% ropivacaine 2 mg?kg-1 (containing adrenaline 5 ?g?ml-1) was injected into epidural space over 2 min. General anesthesia was induced at 30 min after epidural ropivacaine with ?-hydroxybutyrate 60-80 mg?kg-1, remifentanil 2 ?g?kg-1 and atracurium 0.5 mg?kg-1. The patients were intubated and mechanically ventilated. Anesthesia was maintained with inhalation of N2O:O2 (1:1) and intermittent i. v. boluses of atracurium and remifentanil infusion when needed. Pinprick sensory level, onset of analgesia and degree of motor block (Bromage scale) were assessed. Blood samples were taken from central vein at 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720 min after epidural ropivacaine for determination of plasma concentration of ropivacaine (HPLC). Results The two groups were comparable with respect to F/M ratio, age, body weight, duration of operation, intraoperative blood loss and amount of fluid infused. There was no significant difference in onset time and height of sensory block and degree of motor block. The plasma ropivacaine concentration was significantly higher in group Ⅰ (patients with liver dysfunction) than in group Ⅱ during 180-720 min after epidural ropivacaine. The concentration-time curves in the two groups were fitted to two compartment open pharmacokinetic model. The t1/2? was significantly prolonged, AUC0-t was significantly increased, CL and K10 were significantly decreased in group Ⅰ as compared with group Ⅱ. Conclusions Liver dysfunction does not affect the sensory and motor block produced by ropivacaine within 30 min after epidural injection. The metabolism of ropivacaine is significantly slower in patients with liver dysfunction.