BACKGROUND: Agmatine can enhance the analgesic effect of morphine,and antagonize the tolerant and dependent effect of morphine.OBJECTIVE: To observe the effects of injecting agmatine on the neuronal nitric oxide synthase (nNOS) in hippocampus of morphine withdrawal rats.DESIGN: A randomized controlled experimental study.SETTING: Department of Anesthesiology, the General Hospital of Chinese PLA.MATERIALS: All the experiments were carried out in the Department of anesthesiology, the General Hospital of Chinese PLA between April and July 2004. Eighteen healthy SD rats were randomly divided into saline control group (n=6), morphine group (n=6) and agmatine-treated group (n=6).METHODS: The rats in the saline control group were treated with subcutaneous injection of physiological saline (10 mg/kg), those in the morphine group were treated with 5-day preconditioning, subcutaneous injection of morphine of 10, 20, 30, 40 and 50 mg/kg respectively, twice a day, and those in the agmatine-treated group were treated with subcutaneous injection of agmatine (10 mg/kg) at 30 minutes before morphine was given, but at 6 hours later, before morphine was given for the last time, the rats in the morphine group and agmatine treated group were also given intraperitoneal injection of naloxone (5 mg/kg) to induce morphine withdrawal symptoms.The number of times of the morphine withdrawal symptoms (including physical signs of trembling like a wet dog, chewing, irrigating, drooling, diarrhoea, etc.) were recorded within 1 hour, and the reduction of body mass was calculated according to the different value of body mass before and after the withdrawal symptoms induced by naloxone. The rats were killed under anesthesia after praxiological detection, and then hippocampus was taken out and made into frozen sections, and the nNOS was detected with immunohistochemical staining. The CMIAS systemwas applied for imaging analysis, and the average value of the integral absorbance (A) values in 5visual sights for each section was taken as the integral A value of positive neuron.MAIN OUTCOME MEASURES: ① The detected results of morphine withdrawal symptoms in each group; ② The changes of the nNOS expressions in hippocampus of rats in each group.RESULTS: All the 18 rats were involved in the analysis of results. ① The detected results of morphine withdrawal symptoms in each group: The withdrawal symptoms of trembling like a wet dog, chewing, irrigating, drooling,diarrhoea and reduction of body mass in the agmatine treated group were all obviously lower than those in the morphine group [(2.0±1.3), (5.0±1.1);(0.3±0.4), (1.8±0.7); (3.2±1.2), (6.8±3.1); (0.2±0.4), (1.2±0.9); (2.7±2.1),(6.7±2.1); (6.0±3.0), (12.8±2.7) times, P ＜ 0.01], and close to those in the saline control group (P ＞ 0.05). ② The changes of the nNOS expressions in hippocampus of rats in each group: The positive neurons of nNOS in hippocampus mainly distributed in CA1 region, the cytoplasm was stained buffy, and the round nuclei were stained pale purple by haematine. The immunofluorescent A value of positive neuron in the agmatine-treated group was significantly decreased as compared with that in the morphine group (24.32±8.31, 50.82±15.13, P＜ 0.01), and almost the same as that in the saline control group (24.32±8.31, 15.24±1.88, P ＞ 0.05).CONCLUSION: Agmatine can inhibit the morphine withdrawal syndrome and decrease the expression of nNOS in hippocampus CA1 region of morphine-withdrawal rats. Hippocampal nitric oxide pathway takes part in the inhibitory effect of agmatine on morphine withdrawal syndrome.

Objective To establish a model of bone cancer pain in rats and to evaluate the role of voltage gated sodium channel Nav1.8 in the course of bone cancer pain by observing the expression of Nav1.8 in dorsal root ganglion in the model with bone cancer pain.Method Female SD rats received intra-tibial injection of syngenetic Walker256 mammary gland carcinoma cells in different concertration(103/?l,104/?l or 105/?l).Pain threshold of mechanical hyperalgesia and thermal hyperalgesia were tested at 1d,3d,5d,7d,10d,and 14d after cell injection.The development of the bone tumor was verified by pathological examination 14d after cell injection.The L5-6 DRG was obtained from normal rats and rats with bone cancer pain.Expression of voltage gated sodium channel Nav1.8 was investigated by RT-PCR.Result Intra-tibial injection of Walker256 cells produced a rapidly expanding tumor within the boundaries of the tibia,causing marked remodeling of the bone.Rats receiving intra-tibial injection of Walker256 cells displayed gradual development of both mechanical and thermal hyperalgesia 7-14 days after the injection.The expression of Nav1.8 in DRG was up-regulated in the model of bone cancer pain in rats(P

AIM:To investigate the effects of propofol on potassium currents in pulmonary artery smooth muscle cells of normotensive and hypertensive rats. METHODS: The effects of propofol on potassium currents in smooth muscle cells derived from normotensive and hypertensive rats pulmonary arteries were observed by patch clamp technique (whole cell recording) after application of the drug in the bath. RESULTS: The potassium current-voltage curves (I-V curves) of smooth muscle cells derived from normotensive and pulmonary hypertensive rats pulmonary arteries were up-ward shifted by propofol (50, 100 ?mol/L). Compared with control group, within 5 minutes after application of the drug, the current amplitude could increase to (121?11)%, (113?5)% (P

0.05).Intracellular Ca2+ FI in rat ventricular myocytes induced by KCl was inhibited significantly in group B2 and B3 compared with that in group C(P

0.05). Propofol increased laser durations of mice in a dose-dependent manner in group P2 and group P3 (P0.05). Compared to group STP2 and group STP3,the laser duration of mice in group P1 and gourp P3 were prolonged (P0.05). Conelusion:PropofoI at subhypnotic doses may have effective analgesic effect to CO, laser induced-pain in a dose-dependent manner.

Objective To study the effects of subsrachnoid implantation of APA microcapsules-filled with bovine chromaffin cells (BCCs) on expression of mRNA for ?2 and ?2 subunits of GABAA receptor in spinal cord in rats with chronic constrictive injury (CCI) of sciatic nerve and to determine if GABAA receptor is involved in the mechanisms of analgesia produced by subarachnoid implantation of micro-capsulized BCCs. Methods Twenty SD rats weighing 200-250 g were randomly divided into 4 groups with 5 animals in each group : (Ⅰ) control group (group C); (Ⅱ) CCI group in which right sciatic nerve was loosely ligated; (Ⅲ) APA group in which 500-600 empty APA micro-capsules were implanted in subarachnoid space and (Ⅳ) APA-BCC group in which 5?106 APA micro-capsules filled with BCCs were implanted in subarachnoid space. In group Ⅲ and Ⅳ subarachnoid implantation was performed at L1-3 level 7 days after CCI operation. Pain threshold to mechanical stimulation with Von-Frey filament and thermal stimulation with CO2 laser was measured before and 7 days after implantation. Expression of mRNA for GABAA receptor ?2 and ?2 subunit in spinal cord was measured by RT-PCR.Results The expression of mRNA for GABAA receptor ?2 and ?2 subunit in spinal cord was significantly lower in CCI and APA groups (group Ⅱ and Ⅲ) than that in control group (group Ⅰ). In APA-BCC group (group Ⅳ) pain threshold of surgical side to mechanical and thermal stimuli and the expression of mRNA for GABAA receptor ?2 and ?2 subunit in spinal cord were significantly higher than those in group Ⅱ and Ⅲ . Conclusion The expression of mRNA for GABAA receptor?2 and ?2 subunit in spinal cord is down-regulated by CCI and subarachnoid implantation of micro-capsulized BCCs can reverse the down-regulation. Recovery of GABAA-nergic neuron activity contributes to the analgesic effect of aubarachnoid implantation of micro-capsalized BCCs.

AIM To invesigate the effect of subarachnoid transplantation of APA microcapsulized bovine chromaffin cells (BCCs) on mRNA expression for Nav1.8 in the dorsal root ganglia neurons(DRG) of rats with neuropathic pain by means of in situ hybridization. METHODS SD rats were randomly divided into four groups of five. Normal rats were used as control group (group C). Rats with right sciatic nerve been ligated were used as CCI group. Five to six hundred empty APA microcapsules(group APA) or 5?10 6 APA microcapsulized BCCs (group APA-BCCs) were grated into subarachnoid space of CCI rats 7 days after operation. Allodynia and hyperalgesia were measured by Von-Frey filaments and CO 2 laser 7 days after transplantation. DRG in lumbar four and five was taken out and 15 ?m freezing sections were made 7 days after tansplantation. Sections was used to detect mRNA expression for TTX-resistent Na + Nav1.8 by in situ hybridization with Dig-labeled RNA probe. RESULTS The mRNA hybridization signal for Nav1.8 in DRG of group CCI and group APA was lower than that of group C. The expression of mRNA for Nav1.8 in DRG was higher in group APA-BCCs than that in group CCI and group APA with abatement of allodynia and hyperalgesia. There was no difference in the mRNA hybridization signal for Nav1.8 in DRG between group APA-BCCs and group C. CONCLUSION mRNA expression for Nav1.8 in DRG of CCI ratswas down-regulated. APA microcapsulized BCCs grafting can reverse the down-regulation of mRNA expression for Nav1.8 in DRG of CCI rats. Restoration of mRNA expression for Nav1.8 in DRG contributes to the analgesic effect of subarachnoid transplantation of APA microcapsulized BCCs.

AIM: To observe and compare the effects of Ropivacaine and Bupivacaine on glutamate-evoked currents in cultured rat hippocampus neurons.METHODS: Rat hippocampal neurons were dissociated and cultured.Glutamate-evoked currents were recorded by whole cell patch clamp recording.Effects of Ropivacaine and Bupivacaine on glutamate-evoked currents were observed.Drugs were given by pressure ejection or applicated in the bath.RESULTS: Glutamate(100(mmol?L~(-1))) can activate inward currents in cultured rat hippocampus neurons and this currents could be locked by non-NMDA antagonists DNQX.At concentrations of 10,50,100(mmol?L~(-1)),both Bupivacaine and Ropivacaine could obviously decrease glutamate-evoked currents in cultured rat hippocampus neurons.At higher concentration of 50 and 100(mmol?L~(-1)),the reduced amplitude of glutamate-evoked currents by Ropivacaine was larger than that of by Bupivacaine(P

AIM: To compare the blocking effect of ropivacaine and bupivacaine on sodium channels of rat dosal root ganglia(DRG) using whole cell recording technique. METHODS: Rat DRG neurons were enzymatically isolated , tetrodotoxin-sensitive(TTX-s) and tetrodotoxin-resistant (TTX-r) sodium currents of DRG were recorded by whole cell recording.Drugs were given in bath solution.The concentrations of ropivacaine were 10,30,100, 1 000 ?mol?L~ -1 and bupivacaine were 10,30,100,300 ?mol?L~ -1 . The recording number in each dose group was six. RESULTS: CsCl in extracellular fluid and TEA in intracellular fluid were used to block the potassium channels. Sodium currents were recorded when the holding potential was - 70 mV and a serials of pulse with step 10 mV and duration 70 ms was given.TTX-s sodium channel was recorded in 80.1 % large DRG cells and TTX-r sodium channel was recorded in 92.4 % medium and small DRG cells,of which 56.3 % cells had no response to 1 ?mol?L~ -1 TTX. The half-maximal blocking concentrations of ropivacaine on TTX-r sodium channel was 65.7 ? 6.1 ?mol?L~ -1 , which was much lower than that on TTX-s sodium channel 246.8 ? 11.2 ?mol?L~ -1 (P 0.05 ). CONCLUSION: Ropivacaine preferentially blocks TTX-r sodium channel.Selective blocking of TTX-r and TTX-s sodium channel was one of the reasons of seperation of sensation and motion when it is used in epidural anesthesia.

AIM: To compare the effects of total intravenous anesthesia and balanced anesthesia on stress response on suspensive laryngoscope vocal cords surgery. METHODS: Thirty patients undergone microlaryngeal surgery were randomly divided into two groups(n=15). Analgesia and amnesia slow induction was used in all patiens with nosal incubation. During maintenance of anesthesia, propofol, remifentanil and scopolamine were used in total intravenous anesthesia group(group TIVA); fentanyl, scopolamine and isoflurane were used in balanced anesthesia group(group BAL). Record the data of each group,including base data, after induction, end of tracheal intubation,3 min after intubation, setting the suspensive laryngosopy, 3 min after setting the suspensive laryngosopy, removing the trachea, MAP, HR of each time, the time of recovery. The blood concentrations of epinephrine (E), noradrenalin(NE),cortisol,IL-6 were measured at each time point of base data, end of tracheal intubation, setting the suspensive laryngosopy, 3 min after setting the suspensive laryngosopy. RESULTS: There is no significant difference of HR, MAP, blood concentration of E,NE, cortisol, IL-6 at end of tracheal intubation compared with base data. AT setting the suspensive laryngosopy,3 min after setting the suspensive laryngosopy, HR, MAP, blood concentrations of E, NE, cortisol, IL-6 in group BAL were all higher than that of base data,and were also higher than group TIVA at the same time. The recovery time of group TIVA was shorter than that of group BAL. CONCLUSION: Analgesia and amnesia slow induction with nosal intubaion and maintenance with remifentanil, propofol can inhibit sudden change of hemodynamics and stress response of intubation and setting the suspensive laryngoscope, with quicker recovery .It is an ideal anesthesia method for suspensive laryngoscope vocal cords surgery.