OBJECTIVE:The current study investigated the effects of bone marrow mesenchymal stem cells (BMSCs) on pain behavior in rats with trigeminal neuralgia induced by infraorbital nerve chronic constriction injury (ION-CCI), and the repair effects of BMSCs on pathological changes in trigeminal ganglion demyelination.METHODS:BMSCs or phosphate-buffered saline (PBS) alone were injected around trigeminal ganglion in ION-CCI rats via a rat brain stereotaxic apparatus. Mechanical pain threshold (von Frey test) and face grooming behavior were measured in each group. Recovery of demyelination of trigeminal ganglion was observed via electron microscopy 2 weeks later, and BMSC differentiation was observed via immunofluorescence.RESULTS:Rats in the BMSC group exhibited significant improvements in mechanical pain threshold and face grooming behavior compared with the PBS group. BMSCs could repair demyelinating changes in trigeminal ganglion in ION-CCI rats. Only cells expressing GFAP, S-100, and p75 were observed via immunofluorescence, and no PKH67-labeled BMSCs were observed in the trigeminal ganglion. No BMSC differentiation was observed in the trigeminal ganglion.CONCLUSION:Injection of BMSCs around the trigeminal ganglion could relieve trigeminal neuralgia effectively and repair trigeminal ganglion demyelination. No differentiation of BMSCs injected around the trigeminal ganglion into Schwann cells was observed. The mechanism of trigeminal neuralgia demyelination repair requires further investigation.

Objective To explore the effects of isoflurane on blood plasma metabolites (BPM) and its correlation with cognitive dysfunction.Methods Thirty female Sprague-Dawley (SD) rats were randomly divided into two groups:rats in the control group (n =10) received 80％ oxygen for 2 hours (h);and rats in the isoflurane-treated group (n =20) were anesthetized with isoflurane and 80％ oxygen for 2 h.Cognitive functions were examined using a Y-maze test to explore the learning times of rats.The level of blood plasma metabolites was detected through gas chromatography-mass spectrometry (GCMS).Results The learning times of rats in the isoflurane-treated group was more than the learning times of rats in the control group [(70.75 ± 15.30) vs (45.40 ± 11.21),P ＜ 0.05].D-fructose,arabinofuranose,n-butylamine,and inositol significantly increased (P ＜ 0.05),respectively.Whereas,L-analine and L-proline significantly decreased (P ＜ 0.05) in isoflurane-treated rats when compared to those in the control rats (P ＜ 0.05).Moreover,plasma concentrations of d-fructose,arabinofuranose,n-butylamine,inositol,and L-proline were positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats.Conclusions Changes of plasma concentrations of inositol,and d-fructose in aged rats are useful in predicting the occurrence and progression of post-anesthesia cognitive dysfunction.

Nitroglycerin (glyceryl trinitrate, GTN) has been used for more than a century as an excellent agent for the treatment of ischemic heart disease and congestive heart failure. It is commonly believed that the benefit of GTN, credited to supply of its final metabolic product, nitric oxide (NO), is achieved through the NO–cGMP pathway [ 1 Curtis M.J. Pabla R. Nitric oxide supplementation or synthesis block – which is the better approach to treatment of heart disease?. Trends Pharmacol. Sci. 1997; 18: 239-244 PubMed Scopus (33) Google Scholar ]. Nevertheless, the long-term efficacy of GTN is blunted because of the development of nitrate tolerance. Unfortunately, the mechanisms of these effects of GTN are not completely clear. Recent findings in our laboratory and results reported by others show that the neuropeptide calcitonin gene-related peptide (CGRP), hitherto the most potent endogenous vasodilator identified, not only exerts effect in mediating GTN-induced myocardial protection but is also associated with GTN pharmacological tolerance in patients.

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

PURPOSE:Postoperative cognitive dysfunction (POCD) is a formidable public health issue, which would not only affect the quality of life among elderly patients but also lead to pulmonary infection and increased mortality. While, there is a lack of an effective indicator in predicting POCD. As one pivotal part of the limbic system in brain, hippocampus is associated with cognitive function. Hippocampal atrophy could indicate the degree of changes in cognitive function.METHODS:Forty-one ASA II or III patients (23 male, 18 female) aged ≥65 years undergoing open gastrointestinal tract surgery were enrolled in this study. MRI was performed to measure the volume of hippocampal formation before surgery and the results were standardized according to individual intracranial volume. All patients underwent a battery of neuropsychological tests including sensitive tests on the Wechsler adult memory scale and Wechsler adult intelligence scale, trail making test and the grooved pegboard test. We used the Z score to identify POCD as recommended by ISPOCD. All patients were then divided into POCD group and non-POCD group according to the results of the neuropsychological tests. The results of the tests were correlated with the volume of hippocampal formation measured by MRI. The value of MRI measurement of hippocampal volume in predicting POCD was analyzed. Multivariate linear correlation analyses of compositive Z score using potential contributing factors such as age, duration of anesthesia, education and hippocampal volume was carried out.RESULTS:Thirty-six patients completed the whole battery of neuropsychological tests after surgery. Thirteen of the 36 patients were found to have POCD (36 %) on the postoperative 4th day. The hippocampal volume was significantly smaller in POCD group (4.75 ± 0.23) than in non-POCD group (5.06 ± 0.31). Hippocampal volume had great influence on Z score, and had negative correlation with Z score.CONCLUSION:The MRI measurement of hippocampal volume is suggested to be valuable as a predictor of POCD in the elderly.

The present study aimed to investigate the effect of cytochrome P450 3A4 (CYP3A4)*18B polymorphisms and the interaction of the µ opioid receptor gene (OPRM1) A118G and CYP3A4*18B polymorphisms on postoperative fentanyl analgesia in Chinese Han patients undergoing radical gastrectomy. In total, 97 patients scheduled to undergo radical gastrectomy under general anesthesia were enrolled in this study. Post‑operative patient‑controlled intravenous analgesia of fentanyl was administered as analgesia up to 48 h following surgery. Venous blood (2 ml) was obtained from each patient to measure the OPRM1 A118G and CYP3A4*18B genotypes. The differences in fentanyl consumption and adverse effects were compared among the genotypes at 24 and 48 h following surgery. In the first 48 h following surgery, patients in the CYP3A4*18B/*18B group consumed significantly less fentanyl compared with patients in the *1/*1 group (P=0.032). With regards to the joint genetic effect, during the 48‑h period, patients with AA and *1*18B polymorphisms received fewer fentanyl doses compared with those with AG and *1*1 (P=0.049), while patients with AG and *1*18B polymorphisms received significantly fewer fentanyl doses compared with those with AG and *1*1 (P=0.010), and patients with *18B*18B polymorphisms received significantly fewer fentanyl doses compared with those with AA and *1*1 (P=0.024) or those with AG and *1*1 polymorphisms (P=0.006). No correlation between OPRM1 A118G and CYP3A4*18B and postoperative nausea, vomiting and dizziness was found. Results demonstrated that 48 h following surgery, patients with the CYP3A4*18B/*18B genotype required less fentanyl than patients with the CYP3A4*1/*1 genotype to control pain. Additionally, the combined genotype of CYP3A4*18B and OPRM1 A118G may affect fentanyl doses administered for pain control, but not postoperative nausea, vomiting and dizziness.

The aim of this study was to investigate the effect of the μ-opioid receptor gene (OPRM1) A118G polymorphism on the requirement for post-operative fentanyl analgesia in patients undergoing radical gastrectomy. One hundred and twenty-eight gastric cancer patients scheduled to undergo radical gastrectomy under general anesthesia were enrolled in the study. Post-operative, patient-controlled intravenous analgesia of fentanyl was provided for satisfactory analgesia until 48 h after surgery. OPRM1 A118G was screened by DNA sequence analysis of polymerase chain reaction (PCR)-amplified DNA. Differences in fentanyl consumption and adverse effects were compared among the different genotypes at 24 and 48 h after surgery. The ranges of fentanyl dose in the 128 patients at 24 and 48 h after surgery were 5.4-17.3 μg/kg and 12.4-29.9 μg/kg, respectively. Among these patients, there were 54 wild-type homozygotes (AA), 53 heterozygotes (AG) and 21 mutant homozygotes (GG). The frequency of the G allele was 0.371 in the OPRM1 polymorphism. There were no significant differences in fentanyl dose or adverse effects, including nausea, vomiting and dizziness, for the OPRM1 A118G polymorphism (P>0.05). The OPRM1 A118G polymorphism does not play a significant role in post-operative fentanyl analgesic dose or post-operative nausea, vomiting and dizziness in patients undergoing radical gastrectomy.

Objective To investigate the effects of isoflurane anesthesia on hippocampus synaptosomes proteome in aged rats.Methods Twenty-seven 22- month-old SD rats weighing 480-550 g were randomly divided into 2 groups: control group (group C,n =6) and isoflurane group (group Ⅰ,n =21 ).In group C inhaled mixed gas containing 80％ oxygen for 2 h.In group Ⅰ the animals were endotracheal intubated after induction by 3％ isoflurane and inhaled 2％ isoflurane and 80％ oxygen for 2 h.Cognition function was evaluated by Y-maze at 24 h after anesthesia and the total training times were recorded.The total training times ＞ 75 was defined as cognitive dysfuction.In group Ⅰ the animals were divided into cognitive dysfuction group (group ⅠA) and non-cognitive dysfuction group (group IB) according to the results of Y-maze test.The animals were sacrificed and their hippocampi were removed and synaptosomes were extracted for two-dimensional gel electrophoresis.The different protein spots were analyzed by mass chromatographic analysis.Results Six rats had cognitive dysfuction (group IA) and another thirteen rats had no cognitive dysfuction (group IB).The total training times were significantly higher in group IA than in groups C and IB( P ＜ 0.05).There was no significant difference in the total training times between groups C and IB (P ＞ 0.05).There were 21 (11/10) different protein spots between groups IB and IA,and 19 (12/7) different protein spots between groups C and IA.Thirty-one protein spots were identified by means of MALDI-TOF-MS.Conclusion The cognitive dysfuction after isoflurane anesthesia in aged rats may be related to the changes of energy metabolism protein,cytoskeletal structure and regulatory protein in synapse of hippocampus.