Objective To investigate the relationship between autophagy in spinal dorsal horn and development of morphine tolerance in rats.Methods Twenty-four healthy male Sprague-Dawley rats,in which intrathecal (IT) catheters were successfully placed,were randomly divided into 3 groups (n =8 each):control group (group C),morphine tolerance group (group M) and morphine + rapamycin as a reinforcing agent for autophagy group (group MR).Morphine tolerance was induced with IT morphine 20 μg twice a day for 7 consecutive days.While the equal volume of normal saline was given in group C.In addition,rapamycin 2.3μg was injected intrathecally at the second injection of morphine on 3rd day lasting for 3 consecutive days in group MR.Mechanical withdrawal threshold (MWT) to yon Frey filament stimulation was measured before IT injection and 30 min after the second IT injection on 1st,3rd,5th and 7th days.The rats were sacrificed 1 h after the last MWT measurement and the L4-6 segment of the spinal cord was removed for determination of the total mammalian target of rapamycin (mTOR) and phosphorylated mTOR(p-mTOR) and autophagy marker protein LC3 Ⅱ expression in spinal dorsal horn by Western blot.The percentage of p-mTOR expression in total mTOR expression was considered as reflection of the activity.Results MWT was gradually decreased with the prolongation of time of IT injection (P ＜ 0.05).Compared with group C,MWT was significantly increased during IT injection,mTOR activity was decreased and LC3 Ⅱ expression was up-regulated in groups M and MR (P ＜ 0.05).Compared with group M,MWT was significandy increased on 3rd,5th and 7th days after IT injection,mTOR activity was decreased and LC3 Ⅱ expression was up-regulated in group MR (P ＜ 0.05).Conclusion Increased autophagy in spinal dorsal horn is the regulatory mechanism of the body during the development of morphine tolerance in rats and can delay the development of morphine tolerance.

Objective To study the behavioral characteristics of a rat model of the levodopa-induced dyskinesia (LID) and the related factors, and to define clinically the relevant methods for assessing akinesia and dyskinesia in LID rats. Methods Unilaterally lesioned rat model of Parkinson′s disease using 6-hydroxydopamine were treated by levodopa and benserazide once daily for 3 weeks, on the 21st day the acute systemic administration of MK-801 was performed 15 min prior to levodopa treatment to observe the behavior (abnormal involuntary movement, rotation behavior and forelimb stepping) and to estimate the quality of AIM by using the rat AIM rating scale. Immunohistochemical technique was used to measure the number of TH-positive neurons in the substantia nigra (SN) and ventral tegmental area (VTA), which was then correlated to the AIM scores. Results Pulsatile treatment with a subthreshold dose of levodopa gradually induced abnormal involuntary movement (AIM), including stereotypy (limb dyskinesia, axial dystonia and masticatory dyskinesia) towards the side contralateral to the dopamine-denervated striatum and increased rotational behavior. The onset of AIM and motor pattern of each subtype was highly stereotypic across individual rats, and the proportion of each subtype was not consistent among individual rats. The number of TH-positive neurons in the VTA, but not in the SN, was significantly decreased in the LID rats compared with the non-LID rats. MK-801 prevented stereotypy but not rotational behavior. Contralateral forepaw performance was signi-ficantly improved after levodopa treatment, but gradually reduced with more and more severe AIM following repeated levodopa therapy. Conclusion Levodopa-induced rat AIM model of PD demonstrated similar properties with the levodopa-induced dyskinesia (LID) in PD patients, and provided an effective tool for LID study. AIM rating and forelimb stepping test are useful for evaluating the dyskinesia and akinesia of PD rats.

0 05)respeetively before induction, which shoued no statistic difference between two groups.AEP index and BIS of two groups after induction were decreased to below 30 a nd 55 respeetively(T 1 vs. T 0 ,P0 01) ) . The changing tendency of the elderly group and the young group were identical a t all time points. Conclusions AEP index can be used for the anesthesia depth monitoring for the elderly without obvious auditory dysfunction during tracheal intubation.

Objective To study the effect of MK801 on behavioral changes and the possible mechanisms. Methods To observe the behavioral changes of levodopa induced dyskinesia (LID) rats during the period of chronic MK801 treatment, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the changes in expression of FosB, preproenkephalin (PPE) mRNA and prodynorphin (PDyn) mRNA in striatum, respectively. Double labling technique including immunohistochemistry of FosB and retrograde HRP transport tracing was used to observe the cell distribution of FosB. Results Pulsatile treatment with levodopa induced Abnormal involuntary movements (AIM) in PD rats, similar to LID in PD patients. FosB positive neurons and expressions of PPE mRNA and PDyn mRNA in striatum of 6-OHDA-lesioned hemisphere were increased in LID rats, and AIM scores of LID rats were reduced by MK801 treatment(41.9?15.6 vs 7.2?3.0), accompanied by the decrease in expressions of FosB and PDyn mRNA, but not PPE mRNA. Neurons immunoreactive for FosB were mainly located in striatonigral neurons which were labeled by cholera toxin-HRP (CT-HRP) injected in the substantia nigra pars reticulata (SNr). Conclusions MK801 could prevent the occurrence of dyskinesias induced by chronic levodopa treatment. The mechanism might be involved in the high expression of immediate early gene FosB and specific gene PDyn on the direct pathway. It suggests that LID might be related to the abnormal activity of direct pathway.

Objective To assess the analgesic effect of continuous infusion of 0.2% ropivacaine with epidural catheter placed at T11-12 or L2-3 after abdominal hysterectomy. Methods Eighty ASA Ⅰ -Ⅱ patients undergoing elective abdominal hysterectomy were randomly divided into 4 groups with 20 patients in each group : in group Al and A2 the epidural catheter was placed at T11-12 and in group Bl and B2 at L2-3 . After surgery two infusion pumps were used. The first pump was used for continuous epidural infusion of 0.2% ropivacaine in the 4 groups. The second pump was used for patient controlled intravenous analgesia (PCIA) with 0.08% lornoxicam in group Al and Bl or with 0.1% morphine in group A2 and B2. The PCIA bolus dose was 1 ml with a lockout time of 5 min. The analgesic effect (assessed using VAS) and the consumption of lomoxicam / morphine were compared among the four groups. Results The ropivacaine consumption was 192 mg during the 24 h after operation in the 4 groups. The lornoxicam and morphine consumption were (3.9?2.8) mg and (4.6?3.5) mg in group Al and A2 with the epidural catheter placed at T11-12 and (7.7?2.5) mg and (7.8?2.4) mg in group B2 and B2 with catheter placed at L2-3.The consumption of lomoxicam or morphine was significantly less with epidural catheter placed at T11-12 than that with epidural catheter at L2-3 (P

Objective To investigate the changes in the expression of connexin 43 ( Cx43) in astrocytes in the spinal dorsal horn in a rat model of chronic neuropathic pain. Methods Twenty male SD rats weighing 200-250 g were randomly divided into 2 groups : (A) chronic constriction injury group (CCI) received 4 loose ligatures placed on the right sciatic nerve according to Xie[5] (n = 10) and (B) sham operation group in which the right sciatic nerve was exprosed but not ligated ( n = 10) . The pain behavior was evaluated and the paw withdrawal thermal latency (PWTL) and paw withdrawal electric threshold (PWET) were measured the day before operation (D0 baseline) and on the 1st, 3rd, 5th, 7th and 14th day after operation (T1 , T3, T5, T7, T14 ) . On the 14th postoperative day the animals were sacrificed and the L4-5 segment of spinal cord was removed for detection of the expression of Cx43 and glial fibrillary acid protein ( GFAP) in the spinal dorsal horn by immuno-histochemistry. Results In CCI group the rats displayed pain behavior after operation and only 2 of them recovered normal behavior on D14 and their PWTL was shortened and PWET lowered after operation compared to the baseline values (D0), while in the sham operation group PWTL and PWET returned to the baseline after D7. The GFAP positively stained area was significantly larger in the right spinal dorsal horn in CCI group (29?7% ) than in sham operation group (19?5% ). The Cx43 positively stained area was 17?3% in CCI group and 4?1 % in sham operation group. Conclusion Cx43 and GFAP expression increase in the astrocytes in the spinal dorsal hom of the affected side in rats with chronic neuropathic pain, suggesting that the astrocytic gap junction may play an important role in chronic neuropathic pain.

0.05 as compared with T3 ) . (3) 3 min after propofol injection OAA/S score dropped to 0 in all patients; AEP index and BIS decreased to 28.97?11 and 50? 11 respectively.Conclusions Induction of anesthesia with intravenous midazolam-fentanyl-propofol is smooth and effective with little circulatory disturbance.

Objective To compare auditory evoked potential index (AEPI) , BIS , heart rate variability (HRV) and spectral edge frequency (SEF) for monitoring the level of analgesia and sedation produced by different analgesic mixture of PCEA. Methods Thirty ASA Ⅰ-Ⅱ patients undergoing upper abdominal surgery under general anesthesia were enrolled in the study.Patients with mental or hearing disorders were excluded. The patients were randomly divided into three groups . The basic analgesic mixture for PCEA was 0.2% ropivacaine + 0.01% morphine in the 3 group and the PCEA regimen was : loading dose 5ml , background infusion 1ml?h-1, bolus dose 1ml and lock-out interval 10 min. The difference among the 3 groups was that the 5ml loading dose contained clonidine l00?g in group Ⅱ or midazolam 2mg in group Ⅲ. The patients were premedicated with phenobartital and scopolamine. Epidural catheter was placed at T9-10 , a test dose of 1 % lidocaine 3-5ml was given to confirm the correct placement of the epidural catheter. General anesthesia was induced with midazolam 0.06mg?kg-1, fentanyl 4?g?kg-1, propofol 0.5mg?kg-1 and vecuronium 0.1mg?kg-1. Anesthesia was maintained after tracheal intubation with isoflurane inhalation and propofol infusion. Patients were transported to PACU after operation.PCEA was started after extubation when the patients was awake and complained of pain. The AEPI, BIS , HRV and SEF values and VAS, OAA/S scores were recorded before induction of anesthesia (T0 ) at the end of surgery (T1), 5, 15, 30 , 60 , 90 min and 2h, 4h, 8h, 20h, 24h after loading dose (T2-12). Results (1) AEPI was significantly higher than the baseline value when the patient was awake and feel pain ( P

Objective Uterine artery embolization (UAE) is a new but well accepted technique for uterine myoma but patients feel severe pain and cramp during and after operation. The purpose of this study was to determine the effectiveness and safety of PCEA with ropivacaine during and after UAE. Methods Eighty ASA 1 - D patients undergoing UAE were randomly divided into four equal groups with twenty patients in each group: group C received oral nimesulide and/or intramuscular pethidine; in group RD0, RD1 and RD2 patients received PCEA with a mixture of 0.2% ropivacaine + 0.004% morphine. An additional 0.005% (RD1 ) or 0.01 % droperidol (RD2 ) was added to the mixture in group RD1 and RD2 . The PCEA regimen consisted of loading dose 6ml, background infusion 2ml/h, bolus dose 2ml and lockout time 10 min. The VAS pain score, Ramsay score, Bruggman comfort score (BCS) and side effects like nausea, vomiting and pruritus were recorded and compared among the 4 groups. Results Pain and cramp in pelvis were common (90% ) during UAE in group C while the patients in groups RD0, RD1 and RD2 felt no pain and cramp. The patients were quiet and cooperative (Ramsay score 2) in group RD0, RD1 and RD2 while the patients in group C were anxious and agitated. The rate of nausea and vomiting was lower in group RD1 and RD2 than that in group C and RD0. No respiratory depression, hypotension and bradyarrliythmia were observed in the four groups. Conclusion PCEA with ropivacaine and morphine can affectively relieve pain during and after UAE with faster recovery and less side effects. PCEA with moderate droperidol (0.005% ) can reduce the rate of natisea and vomiting.

Objective To investigate the effect of dexmedetomidine on norepinephrine(NE)release in midbrain periaqueductal gray(PAG)in a rat model of incisional pain.Methods Twenty-four male Wistar rats in which microdialvsis catheter was successfully placed in the ventrolateral region of PAG without complications were randomly divided into 4 groups(n=6 each):group control(group C);group incisional pain(group IP);group dexmetomidine(group D)and group dexmedetomidine+yohimbine(group DY).Incisional pain was induced by an incision made into the plantar surface of left hindpaw in IP,D,DY groups.Dexmedetomidine 30 μg/kg and dexmedetomidine 30 μg/kg+yohimbine 0.5 mg/kg were given intraperitoneally at 15 min before plantar incision in group D and group DY respectively.Mechanical paw withdrawal threshold(MWT)to von Frey filament stimulation was measured at 30 min before(baseline)and 1,2,3,4 h after operation in C,IP,D groups,and at 30 min before(baseline),and 1 h after operation in group DY.Dialysate samples were collected at 30 min before(baseline)and at evcry 30 min after operation for 4 h via cerebral microdialysis catheter for determination of the NE concentration in C,IP,D groups,and at 30 min before(baseline),30,60 min after operation in group DY.Results Incisional pain significantly decreased MWT and increased the NE concentration in dialysate in group IP.Dexmedetomidine premedication significantly inhibited mechanical hyperalgesia and attenuated incisional pain-induced increase in the NE concentration in dialysate in group D.Yohimbine counteracted effects of dexmedetomidine.Conclusion Dexmedetomidine has analgesic effect though inhibition of NE release from PAG.