κ-Opioid receptors are involved in enhanced cardioprotection by combined fentanyl and limb remote ischemic postconditioning.

BACKGROUND: The combination of various interventions to obtain enhanced cardioprotection is always an important area of research focus. This randomized experiment was designed to assess whether combined fentanyl and limb remote ischemic postconditioning produced enhanced protection against myocardial ischemia/reperfusion injury in an in vivo rat model, and to determine if κ-opioid receptors were implicated in the cardioprotection of these interventions. METHODS: Seventy-two rats were exposed to a 30-min myocardial ischemia followed by a 180-min reperfusion. Half of the rats (36) were randomized into four different groups receiving control treatment, fentanyl postconditioning, limb remote ischemic postconditioning, and combined fentanyl and limb remote ischemic postconditioning. The remaining 36 rats were also randomized into four groups receiving the same interventions as the above groups following the intravenous administration of a κ-opioid receptor antagonist, nor-binaltorphimine, before myocardial ischemia. At the end of reperfusion, both serum cardiac troponin I and infarct size were determined. RESULTS: Both fentanyl postconditioning and limb remote ischemic postconditioning significantly decreased the infarct size and serum cardiac troponin I level, and combined fentanyl and limb remote ischemic postconditioning produced enhanced cardioprotection on the infarct size-sparing effect. The use of nor-binaltorphimin to block κ-opioid receptors eliminated cardioprotection by fentanyl postconditioning and enhanced cardioprotection by combined fentanyl and limb remote ischemic postconditioning, but did not change cardioprotection by limb remote ischemic postconditioning. CONCLUSIONS: Combined fentanyl and limb remote ischemic postconditioning produced enhanced protection against myocardial ischemia/reperfusion injury. κ-Opioid receptors are essential for cardioprotection by fentanyl postconditioning and enhanced cardioprotection by combined fentanyl and limb remote ischemic postconditioning; however, they do not play a pivotal role in cardioprotection by limb remote ischemic postconditioning.

[Effects of combined ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats].

OBJECTIVE: To assess the effects of ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats. METHODS: A total of 110 adult SD rats were randomly divided into 5 groups (n = 22 each). The focal cerebral ischemia-reperfusion injury was induced by a 90-minute occlusion of right middle cerebral artery (MCA) and a 24-hour reperfusion sequentially. Group 1 was of ischemia-reperfusion control; Group 2 ischemic postconditioning induced by three 30-second cycles of MCA occlusion followed by a 30-second reperfusion; Group 3 remote ischemic postconditioning performed via a transient occlusion of right femoral artery at 5 min before the initiation of reperfusion; Group 4 naloxone postconditioning with naloxone 10 mg/kg intraperitoneally injected at the initiation of reperfusion; Group 5 combined ischemic, remote ischemic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2, 3 & 4. The neurologic deficit scores (NDS) were obtained at 2 h & 24 h post-reperfusion. At 24 h post-reperfusion, the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to assess the size of cerebral infarct (n = 10), detect the cerebral expression of microtubule-associated protein-2 (MAP2) (n = 6), measure the plasma volume of cerebral tissues and quantify the diameter and segment length of cerebral microvessel (n = 6). RESULTS: There were no significant differences in the heart rate (HR) and mean arterial pressure (MAP) among the above five groups at all observed time points (P > 0.05). At 24 h post-reperfusion, the percentage of ischemic cerebral infarct size was 43% ± 6%, 31% ± 4%, 32% ± 5%, 28% ± 6% & 21% ± 7% in ipsilateral hemisphere area (i.e., cerebral infarct severity) in Groups 1-5 respectively. Compared with Group 1, the levels of NDS and cerebral infarct severity significantly decreased at ischemic side in Groups 2-5 (P < 0.05). And the cerebral expression of MAP2, plasma volume of cerebral tissues, diameter and segment length of cerebral microvessel significantly increased at the ischemic side (all P < 0.05). However, there were no significant differences in the above-mentioned parameters at ischemic side among Groups 2, 3 and 4 (all P > 0.05). The parameters of NDS, cerebral infarct severity, cerebral expression of MAP2 and plasma volume of cerebral tissues in the ischemic side significantly increased in Group 5 compared with Groups 1, 2, 3 and 4 (all P < 0.05). The diameter and segment length of cerebral microvessel at ischemic side were not different among Groups 2, 3, 4 and 5 (all P > 0.05). CONCLUSION: In focal cerebral ischemia-reperfusion rats, ischemic, remote ischemic and naloxone postconditioning may produce significant neuroprotective effects of reduced cerebral infarct severity and improved neurologic dysfunctions. A combination of three postconditioning approaches enhances the above neuroprotective effects.

Bolus dose remifentanil and sufentanil blunting cardiovascular intubation responses in children: a randomized, double-blind comparison.

BACKGROUND AND OBJECTIVE: The present randomized controlled study was designed to compare the efficacy of remifentanil 2 microg kg(-1) and sufentanil 0.2 microg kg(-1) by bolus injection on the cardiovascular response to intubation in healthy children. METHODS: One hundred and five children, ASA 1-2 and scheduled for elective plastic surgery under general anaesthesia, were randomly divided into one of two study groups to receive the following treatments in a double-blind manner: remifentanil 2 microg kg(-1) (group R) and sufentanil 0.2 microg kg(-1) (group S). Blood pressure and heart rate (HR) were recorded before anaesthesia induction (baseline values), immediately before intubation (postinduction values), at intubation and every minute for 5 min after intubation. The percentage changes in systolic blood pressure (SBP) and HR relative to baseline values were calculated. The incidences of SBP and HR percentage changes of more than 30% of baseline values during the observation were recorded. RESULTS: As compared with baseline values, blood pressure and HR at intubation and their maximum values during the observation increased significantly in group S, but decreased significantly in group R. Blood pressure and HR at intubation and their maximum values during the observation were significantly different between the groups. There were significant differences between the groups in the percentage changes of SBP and HR relative to baseline values and their maximum percentage changes during the observation. The incidences of SBP and HR percentage increases of more than 30% of baseline values were not significantly different between the groups, but the incidences of SBP and HR percentage decreases of more than 30% of baseline values were significantly higher in group R than in group S. CONCLUSION: In combination with propofol for anaesthesia induction in children, sufentanil 0.2 microg kg(-1) by bolus injection fails to depress the cardiovascular intubation response. Remifentanil 2 microg kg(-1) by bolus injection can completely abolish the cardiovascular intubation response, but causes more adverse cardiovascular depression.

[Effect of remifentanil preconditioning on myocardial ischemia-reperfusion injury].

OBJECTIVE: To investigate the delayed cardioprotection induced by remifentanil in intact rat ischemia-reperfusion (I/R) models. METHODS: Totally 42 adult male Wistar rats weighing 200-300 g were randomly divided into 7 groups (n = 6 in each group): In Group I, rats were injected with normal saline via tail vein, performed with the regimen of 3 x 5-min intravenous (i.v.) infusion at a rate of 0.1 ml x kg(-1) min(-1) 24 h before I/R; In Group II, rats were treated according to the same experimental protocols as in Group I except receiving additional naloxone (0.1 mg/kg) 10 minutes before normal saline pretreatment; In Groups III, IV, V, and VI, rats were treated with remifentanil via tail vein, performed with the regime of 3 x 5-min i.v. infusion at a rate of 2 microg x kg(-1) x min(-1) 12 h, 24 h, 48 h, and 72 h before I/R; In Group VII, the rats were treated according to the same experimental protocols as in Group IV except that they received additional naloxone (0.1 mg/kg) 10 minutes before remifentanil pretreatment. Heart rate (HR), mean arterial pressure (MAP), and a lead II electrocardiogram were continuously monitored during IR process. To determine plasma concentration of creatine kinase myocardial isoenzyme-MB (CK-MB), arterial blood samples were obtained immediately before ischemia, and at the end of ischemia and reperfusion. After a 120-min reperfusion, heart was removed for the measurement of myocardial infarct size. Infarct size (IS) was expressed as percentage of the area at risk. RESULTS: HR, MAP, and rate-pressure product were not significantly different at each time points among all groups (P > 0.05). Compared with Group I, plasma concentrations of CK-MB at the end of ischemia and reperfusion and myocardial infarct size were significantly lower in Groups IV and V (P < 0.05). Compared with Group IV, plasma concentrations of CK-MB at the end of ischemia and reperfusion were significantly higher and myocardial infarct size was significantly larger in Group VII (P < 0.05). CONCLUSION: Remifentanil preconditioning induces delayed cardioprotection in intact rat ischemia-reperfusion model, which may be triggered via opioid receptors.

A new air- and moisture-stable pentagonal-bipyramidal DyIII single-ion magnet based on the HMPA ligand.

Based on the HMPA ligand, a new air- and moisture-stable pentagonal-bipyramidal DyIII single-ion magnet [Dy(HMPA)2(H2O)5]2·Br6·2HMPA·2H2O (1) was prepared and characterized. Single-crystal X-ray tests showed the two crystallographically independent DyIII ions located in a pentagonal-bipyramidal coordination sphere with strong axial HMPA ligands and weak equatorial water molecules relating to strong unaxial anisotropy. Direct-current and alternating-current magnetic susceptibilities were measured and showed that 1 exhibited slow relaxation of magnetization up to 36 K (1000 Hz) with an energy barrier of 556 K and blocking temperature of 7 K (defined by the peak temperature of zero-field cooling data). The application of a dc field and magnetic dilution were also carried out to explore the existing quantum tunelling of the magnetization process.

Clinical experience of airway management and tracheal intubation under general anesthesia in patients with scar contracture of the neck.

BACKGROUND: Because patients with scar contracture of the neck are at a high risk of loss of the airway control after anesthesia induction, awake intubation is usually recommended. This retrospective clinical study was designed to evaluate the possibility, safety and efficacy of airway management and tracheal intubation under general anesthesia in such patients. METHODS: This retrospective study included 1683 patients from January 1994 to December 2006 with scar contracture of the neck, aged 1.5 - 67.0 years, who were scheduled for elective plastic surgery under general anesthesia in Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Based on the results of the preoperative airway assessment, the patients were classified into group 1 (including 1375 patients with the atlanto-occipital extension of > 20 degrees and the Mallampatti's grade I or II) and group 2 (containing 308 patients with the atlanto-occipital extension of < 20 degrees and the Mallampatti's grade III or IV. In group 1, the intravenous induction and maintenance of anesthesia and succinylcholine for muscle relaxation were used. The intubation was done using a modified Macintosh technique. In group 2, the total intravenous anesthesia (TIVA) or the sevoflurane inhalation anesthesia was chosen and the spontaneous breathing was reserved during anesthesia. The intubation was performed by a fiberoptic stylet laryngoscope (FOSL). The number of intubation attempts, intubation time and relative complications were observed and recorded in all patients. RESULTS: In group 1, the intubation was accomplished during the first attempt in 1279 cases (93%) and the intubation time was < 3 minutes in 1304 cases (95%). In group 2, the intubation was completed by the first attempt in 114 patients (37%) and 123 patients had an intubation time of < 3 minutes (40%). Tracheal intubation was successful by the second or third attempt in 96 patients in group 1 and 156 patients in group 2. Thirty-eight patients required four or more attempts which only occurred in group 2. The incidence of traumatic complication was 2.6% and 9.7% with one intubation attempt in groups 1 and 2, respectively, 12.5% and 17.0% with multiple intubation attempts (one vs multiple attempts in both groups, P < 0.001). All non-traumatic complications occurred in group 2 and laryngospasm and hypoxemia were more common in patients using the TIVA compared to those using the sevoflurane inhalational anesthesia (P < 0.001). CONCLUSIONS: This study demonstrated that with a precise airway evaluation, an adequate preoperative preparation and a pre-planned failed intubation strategy, the anesthetist who was experienced in the difficult airway management could safely perform airway control and tracheal intubation under general anesthesia in patients with scar contracture of the neck. We believe that this technique may be very valuable for the management of a known difficult airway because it is comfortable for the patient and saves time for the anesthetist.

Circulatory responses to nasotracheal intubation: comparison of GlideScope videolaryngoscope and Macintosh direct laryngoscope.

BACKGROUND: The GlideScope videolaryngoscope (GSVL) has been shown to have no special advantage over the Macintosh direct laryngoscope (MDL) in attenuating the circulatory responses to orotracheal intubation, but no study has compared the circulatory responses to nasotracheal intubation (NTI) using the two devices. This prospective randomized clinical study was designed to determine whether there was a clinically relevant difference between the circulatory responses to NTI with the GSVL and the MDL. METHODS: Seventy-six adult patients were randomly allocated equally to the GSVL group and the MDL group. After induction of anesthesia, NTI was performed. Non-invasive blood pressure (BP) and heart rate (HR) were recorded before induction (baseline values) and immediately before intubation (post-induction values), at intubation and every minute for a further five minutes. During the observation, times required to reach the maximum values of systolic BP (SBP) and HR, times required for recovery of SBP and HR to postinduction values and incidence of SBP and HR percent changes > 30% of baseline values were also noted. The product of HR and systolic BP, i.e. rate pressure product (RPP), and the areas under SBP and HR vs. time curves (AUC(SBP) and AUC(HR)) were calculated. RESULTS: The NTI with the GSVL resulted in significant increases in BP, HR and RPP compared to postinduction values, but these circulatory changes did not exceed baseline values. BPs at all measuring points, AUC(SBP), maximum values of BP and incidence of SBP percent increase > 30% of baseline value during the observation did not differ significantly between groups. However, HR and RPP at intubation and their maximum values, AUC(HR) and incidence of HR percent increase > 30% of baseline value were significantly higher in the MDL group than in the GSVL group. Times required for recovery of SBP and HR to postinduction values were significantly longer in the MDL group than in the GSVL group. CONCLUSIONS: The pressor response to NTI with the GSVL and the MDL was similar, but the tachycardiac response to NTI was lesser and of a shorter duration when using a GSVL than when using an MDL.

[Comparison of cardiovascular responses between orotracheal and nasotracheal intubation with the aid of GlideScope video laryngoscope].

OBJECTIVE: To compare the cardiovascular responses to orotracheal or nasotracheal intubation with the aid of GlideScope video laryngoscope (GSVL). METHODS: Sixty patients, American Society of Anesthesiologists (ASA) physical status I, aged 16-50 years, scheduled for elective plastic surgery under general anesthesia,were randomly allocated equally to the orotracheal intubation group (OTI group) and the nasotracheal intubation group (NTI group). After the routine anesthesia induction, orotracheal and nasotracheal intubation was respectively performed with the aid of GSVL. Non-invasive blood pressure and heart rate (HR) were recorded before (baseline values) and after anesthesia induction (postinduction values), during intubation and every minute for 5 minutes after intubation. Maximum values of blood pressure and HR during the observation periods were recorded. The product of HR and systolic blood pressure [rate pressure product (RPP)] at every time point was calculated. Duration for glottis exposure and duration for successful intubation were also noted. RESULTS: There were no significant differences between two groups in the demographic data (P>0.05). Glottis exposure time and intubation time in NTI group were significantly longer than those in OTI group [(52.2+/-13.5) seconds vs. (40.5+/-15.2) seconds, P<0.05]. After anesthesia induction, blood pressure and RPP in both groups decreased significantly compared with baseline values, but no significant change in HR was noted. Compared with their postinduction values, the blood pressure and RPP in both groups and HR in OTI group increased significantly at intubation. In OTI group,the maximum values of HR, diastolic blood pressure (DBP), mean arterial pressure (MAP), RPP exceeded their baseline values. But in NTI group,only maximal HR during the observation period was significantly higher than the baseline values. The blood pressure at every time point was not significantly different between two groups. But intubation in OTI group caused significant increases in HR and RPP compared with those in NTI group (both P<0.05). CONCLUSION: In anesthetized adult patients, orotracheal and nasotracheal intubations with the GSVL can result in a similar pressor response, however orotracheal intubation with GSVL causes more marked cardiovascular responses than nasotracheal intubation with the aid of GSVL.

[Comparison of hemodynamic responses to nasotracheal intubations with Glide Scope video-laryngoscope, Macintosh direct laryngoscope, and fiberoptic bronchoscope].

OBJECTIVE: To compare the hemodynamic responses to nasotracheal intubation with Glide Scope video-laryngoscope (GSVL), Macintosh direct laryngoscope (MDLS), and fiberoptic bronchoscope (FOB). METHODS: Sixty patients, with American Society of Anesthesiologists (ASA) physical status I - II, aged 18- 50 years, and scheduled for elective plastic surgery under general anesthesia requiring nasotracheal intubation, were randomly allocated equally to GSVL group, MDLS group, and FOB group. After the routine anesthesia induction, nasotracheal intubation was performed with the GSVL, MDLS, and FOB, respectively. Noninvasive blood pressure (BP) and heart rate (HR) were recorded before (baseline values) and after anesthesia induction (postinduction values), at intubation, and subsequently at an interval of every 1 minute for a total of five minutes. The maximum and minimum values of BP and HR during the observation period were also noted. The rate pressure product (RPP) at each measuring time point was calculated. The areas under effect-time curve (AUE) of hemodynamics were calculated by time as X-axis and changes of BP and HR during the observation as Y-axis. RESULTS: All the three groups were similar in the demographic data and intubation time. After anesthesia induction, BP and RPP in all the three groups decreased significantly compared to baseline values (P < 0. 05), while HR had no significant change. After nasotracheal intubation, BP, HR, and RPP in all three groups were significantly higher than the postinduction values (P < 0.05). In the FOB group, BP, HR, and RPP at intubation significantly increased when compared with the baseline values (P < 0.05). In the MDLS group, HR at intubation, and maximum values of diastolic blood pressure (DBP), mean arterial pressure (MAP), HR, and RPP during the observation were significantly higher than the baseline values (P < 0.05). In the GSVL group, all hemodynamic parameters at intubation and after intubation were not significantly different from the baseline values. BP, HR, and RPP at intubation, and the incidences of HR more than 100 bpm during the observation were significantly higher in the FOB group than in the other two groups (P < 0.05). BP was not significantly different during the observation between the MDLS and GSVL groups, but HR and RPP at intubation and after intubation as well as AUE(HR) were significantly higher in the MDLS group than in the GSVL group (P < 0.05). AUE(HR) and AUE(SBP) were significantly lower in the GSVL group than in the FOB group (P < 0.05). CONCLUSION: The hemodynamic responses to nasotracheal intubation are most severe with FOB, followed by MDLS, and then GSVL.

[Influence of pressure on cricoid on insertion ProSeal laryngeal mask airway and ventilation function].

OBJECTIVE: To assess the influence of cricoid pressure (CP) on insertion and ventilation function of ProSeal laryngeal mask airway (PLMA). METHODS: Fifty adult patients with American Society of Anesthesiologists (ASA) physical status category I, scheduled for elective plastic surgery were studied. After induction of intravenous anesthesia, the PLMA was inserted using an introducer under CP and the intracuff pressure was set to 60 cm H(2)O (1 cm H(2)O=0.098 kPa) with the introducer in place. The content degree of lung ventilation, airway seal pressure and anatomic position of the cuff were assessed. Then CP was temporary terminated, the PLMA was further advanced to the ideal position and the intracuff pressure was readjusted to 60 cm H(2)O. The above-mentioned assessments were re-performed, and the expiratory tidal volume and peak inspiratory pressure during positive-pressure ventilation (PPV) with and without CP were recorded. The gastric tube placement through the PLMA was observed, anatomical position of the drain tube was also scored by fiberoptic examination. RESULTS: After the PLMA was further advanced to the ideal position under temporary termination of CP, lung ventilation content degree (good: acceptable=50:14 cases), airway seal pressure [(27+/-7) cm H(2)O vs. (21+/-7) cm H(2)O] and fiberoptic score of anatomical position of cuff were significantly improved compared with those after PLMA insertion under CP (P<0.05). The expiratory tidal volume during PPV was not significantly different between with and without CP, but the peak inspiratory pressure increased from (14+/-2) cm H(2)O without CP to (28+/-5) cm H(2)O with CP, and there was statistically significant difference (P<0.05). In all patients, gastric tube placement through the PLMA was successful with single attempt and correct anatomical position of the drain tube was confirmed by fiberoptic examination. CONCLUSION: The CP can impede the insertion of PLMA into the ideal position. The PLMA is still able to be advanced to the ideal position with a special introducer under temporary termination of CP. After the PLMA is advanced to the ideal position, the CP produces a significant increase in the peak inspiratory pressure during PPV.

[An auto control comparison of the use of ProSeal laryngeal mask airway and standard laryngeal mask airway for positive pressure ventilation].

OBJECTIVE: To compare the ProSeal laryngeal mask airway (PLMA) and the standard laryngeal mask airway (SLMA) for intermittent positive pressure ventilation (IPPV) in a randomized auto control design. METHODS: Fifty adult patients with American Society of Anesthesiologists (ASA) physical status 1-2, scheduled for elective plastic surgery under general anesthesia were recruited. After the routine intravenous anesthesia induction, the PLMA and the SLMA were inserted randomly in sequence into each patient and inflated to an intracuff pressure of 60 cm H(2)O (1 cm H(2)O=0.098 kPa), airway seal pressure and lung ventilation satisfaction were evaluated, and fiberoptic (FOB) scores of the cuff anatomic position were measured. The mean expired volume and the mean peak inspiratory pressure of five continuous breaths were calculated after IPPV with 10 ml/kg tidal volume was performed. RESULTS: Without cuff inflation, airway seal pressure was higher with the PLMA than with the SLMA (P<0.05), and adequate or acceptable lung ventilation was obtained in 46 (92%) patients with the PLMA, but only 22 (44%) patients with the SLMA. When the air volume required to obtain an intracuff pressure of 60 cm H(2)O, adequate lung ventilation was obtained in 50 patients with the PLMA, but only 28 patients with the SLMA, and the inflation volume and sequential airway seal pressure were higher with the PLMA than with the SLMA (both P<0.05), and the airway seal pressure with the PLMA was not less than with the SLMA in each patient. The ventilation volume was higher with the PLMA than with the SLMA, except in 2 patients. The FOB score of the cuff position was lower with the PLMA than with the SLMA (P<0.05). The mean expired tidal volume and the mean peak inspiratory pressure were not significantly different between 29 patients with the PLMA and 21 patients with the SLMA for airway maintenance during operation (both P>0.05). CONCLUSION: Compared with SLMA, PLMA can achieve a higher airway seal pressure and potentially isolate the glottis and the upper esophagus, and is safer and more effective for positive pressure ventilation.

[N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats].

The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in group 3, but the expressions of the NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4. As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA were significantly inhibited in group 6. These results suggest that the expressions of nNOS and NMDA receptors in spinal cord and midbrain were significantly up-regulated in the rats with morphine analgesia tolerance. Chronic co-administration of L-NAME could effectively inhibit the morphine-induced overexpressions of nNOS and NMDA receptors, and postpone the development of morphine analgesia tolerance. Based on the results of this study, it is concluded that NO/NMDA receptor in spinal cord and midbrain is closely related to the development of morphine analgesia tolerance.