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Objective:To evaluate the relationship between autophagy and oxidative stress during remifentanil-induced hyperalgesia in the rats with incisional pain.Methods:Thirty-two clean-grade healthy male Sprague-Dawley rats, weighing 230-250 g, aged 2-3 months, were divided into 4 groups ( n=8 each) using a random number table method: incisional pain group (I group), remifentanil + incisional pain group (RI group), autophagy inhibitor 3-methyladenine + remifentanil + incisional pain group (MRI group) and autophagy agonist rapamycin group + remifentanil + incisional pain group (RRI group). The model of incision pain was developed and the equal volume of normal saline was intravenously infused simultaneously for 60 min.In RI, MRI and RRI groups, the model of incision pain was developed and remifentanil 1 μg·kg -1·min -1 was simultaneously infused for 60 min.In MRI group, 3-methyladenine 15 mg/kg was intraperitoneally injected at 12 h before developing the model, and rapamycin 10 mg/kg was intraperitoneally injected at 12 h before developing the model in RRI group.Thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before infusion of remifentanil or normal saline (T 0) and at 2, 6, 24 and 48 h after the end of infusion (T 1-4). The rats were sacrificed after the end of behavioral testing, and the lumbar enlargement segments of the spinal cord were harvested for determination of the expression of autophagy microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), Beclin-1 and P62 (by Western blot), activity of superoxide dismutase (SOD) (by xanthine oxidase method) and content of malondialdehyde (MDA) (by thiobarbital method). Results:Compared with the baseline at T 0, PWT was significantly decreased and TWL was shortened at T 1-4 in the four groups ( P<0.05). Compared with I group, MWT was significantly decreased and TWL was shortened at T 1-4, the expression of LC3 Ⅱand Beclin-1 was up-regulated, the expression of P62 was down-regulated, SOD activity was decreased, and MDA content was increased in RI group ( P<0.05). Compared with RI group, MWT was significantly decreased and TWL was shortened at T 1-4, the expression of LC3 Ⅱand Beclin-1 was down-regulated, the expression of P62 was up-regulated, SOD activity was decreased, and MDA content was increased in MRI group ( P<0.05), and MWT was significantly increased and TWL was prolonged at T 1-4, the expression of LC3 Ⅱand Beclin-1 was up-regulated, the expression of P62 was down-regulated, SOD activity was increased, and MDA content was decreased in RRI group ( P<0.05). Conclusions:Autophagy is involved in the process of remifentanil-induced incisional hyperalgesia through regulating the level of oxidative stress in rats.
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Objective To evaluate the role of neuroligin 1 (NL-1) in trafficking of GluR1-containing AMPA receptor to cell membrane in spinal cord dorsal horns during remifentanil-induced hyperalgesia in mice with incisional pain.Methods Forty SPF healthy male C57BL/6J mice,aged 8-10 weeks,weighing 18-22 g,were divided into 5 groups (n=8 each) using a random number table method:control group (group C),NL1-shRNA plasmid group (group NL),incisional pain plus remifentanil group (group I+R),incisional pain plus remifentanil plus blank vector group (group I+R+B),and incisional pain plus remifentanil plus NL-1-shRNA plasmid group (group I+R+NL).Negative lentivirus was intrathecally injected in group I+R+B.In NL and I+R+NL groups,10 μl NL-1-shRNA lentivirus at 1×10s IFU/ml was intrathecally injected once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected at the same time point in C and I+R groups.After transfection was stable,normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at 15 min intervals in C and NL groups.In I+R,I+R+B and I+R+NL groups,0.1 ml remifentanil 10 μg/kg was injected via the caudal vein for 4 consecutive times at 15 min intervals,and the model of incisional pain was established after the first administration.The mechanical paw withdrawal threshold (MWT) and tail-flick latency (TFL) were measured at 24 h before normal saline or remifentanil administration (T0) and at 3,6,24 and 48 h after the end of administration (T1-4).The animals were sacrificed after measurement of pain threshold at T4,and L4-6 segments of the spinal dorsal horn were then collected for determination of the expression of NL-1 protein and mRNA and AMPA receptors,and the ratio of AMPA receptor expression in the membrane protein to that in the total protein (m/t ratio) was calculated.Results Compared with group C,the MWT was significantly decreased,and TFL was shortened at T1-4,the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was up-regulated,and m/t ratio was increased in I+R and I+R+B groups (P＜0.05).Compared with I+R and I+R+B groups,the MWT was significantly increased and TFL was prolonged at T1-4,the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was down-regulated,and m/t ratio was decreased in group I+R+NL (P＜0.05).Conclusion NL-1 in spinal cord dorsal horns can promote the trafficking of GluR1-containing AMPA receptors to cell membrane,which is involved in the development and maintenance of remifentanil-induced hyperalgesia in mice with incisional pain.
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Objective@#To evaluate the role of neuroligin 1 (NL-1) in trafficking of GluR1-containing AMPA receptor to cell membrane in spinal cord dorsal horns during remifentanil-induced hyperalgesia in mice with incisional pain.@*Methods@#Forty SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 5 groups (n=8 each) using a random number table method: control group (group C), NL1-shRNA plasmid group (group NL), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus blank vector group (group I+ R+ B), and incisional pain plus remifentanil plus NL-1-shRNA plasmid group (group I+ R+ NL). Negative lentivirus was intrathecally injected in group I+ R+ B.In NL and I+ R+ NL groups, 10 μl NL-1-shRNA lentivirus at 1×108 IFU/ml was intrathecally injected once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected at the same time point in C and I+ R groups.After transfection was stable, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at 15 min intervals in C and NL groups.In I+ R, I+ R+ B and I+ R+ NL groups, 0.1 ml remifentanil 10 μg/kg was injected via the caudal vein for 4 consecutive times at 15 min intervals, and the model of incisional pain was established after the first administration.The mechanical paw withdrawal threshold (MWT) and tail-flick latency (TFL) were measured at 24 h before normal saline or remifentanil administration (T0) and at 3, 6, 24 and 48 h after the end of administration (T1-4). The animals were sacrificed after measurement of pain threshold at T4, and L4-6 segments of the spinal dorsal horn were then collected for determination of the expression of NL-1 protein and mRNA and AMPA receptors, and the ratio of AMPA receptor expression in the membrane protein to that in the total protein (m/t ratio) was calculated.@*Results@#Compared with group C, the MWT was significantly decreased, and TFL was shortened at T1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was up-regulated, and m/t ratio was increased in I+ R and I+ R+ B groups (P<0.05). Compared with I+ R and I+ R+ B groups, the MWT was significantly increased and TFL was prolonged at T1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was down-regulated, and m/t ratio was decreased in group I+ R+ NL (P<0.05).@*Conclusion@#NL-1 in spinal cord dorsal horns can promote the trafficking of GluR1-containing AMPA receptors to cell membrane, which is involved in the development and maintenance of remifentanil-induced hyperalgesia in mice with incisional pain.
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Objective@#To analyze the efficacy and safety of intervertebral endoscopy in the treatment of double segmental protrusion of lumbar intervertebral disc.@*Methods@#From February 2016 to May 2017, 126 patients with double segment lumbar disc herniation diagnosed in Rizhao Central Hospital were divided into the observation group and the control group according to the different treatment methods, with 63 cases in each group.The observation group was treated with intervertebral foramen technique, and the control group was treated with conventional fenestration.The treatment efficacy of the two groups was compared.The differences of VAS score and ODI between the two groups before and after operation were compared.@*Results@#Compared with the control group, the observation group had shorter hospitalization time[(7.1±3.1)d vs.(11.5±4.2)d], smaller incision length[(1.2±0.3)cm vs.(4.3±1.6)cm], less blood loss[(22.3±8.2)mL vs.(36.3±9.2)mL], there were statistically significant differences between the two groups (t=9.365, 3.965, 5.566, all P<0.05). From preoperation to 6 months after operation, the VAS scores of the two groups showed a significant downward trend.There were statistically significant difference in the VAS scores between the two groups at different time points, between groups and at different time points (F=5.688, 4.589, 3.998, all P<0.05). From preoperation to 6 months after operation, the ODI of the two groups decreased first and then increased, and there was statistically significant difference between the two groups of ODI in different time points (F=4.254, P<0.05). The good rate of curative effect in the observation group was 87.3%, which in the control group was 84.1%, the difference was not statistically significant (χ2=0.259, P>0.05). There was no statistically significant difference in the incidence rate of adverse reactions between the two groups (6.4% vs.9.5%) (χ2=0.434, P>0.05).@*Conclusion@#The treatment of double segment lumbar intervertebral disc herniation with intervertebral foraminoscopy is reliable, with small tissue trauma and mild pain.