OBJECTIVES: There are clinical reports of nerve injury caused by ropivacaine. The mechanism for nerve injury induced by ropivacaine has not been fully clarified. This study aims to investigate the changes of pain threshold and L₃ spinal cord genomics at 6 h and 24 h after intrathecal injection of 0.5% and 1.0% ropivacaine, and to explore the underlying mechanisms for nerve injury caused by ropivacaine. METHODS: A total of 30 male Sprague Dawley rats weighing 220-260 g were successfully implanted with microspinal catheter. The rats were randomly divided into 5 groups (each n=6): a control group (given saline), a ropivacaine group 1 and a ropivacaine group 2 (both given 1% ropivacaine), a ropivacaine group 3 and a ropivacaine group 4 (both given 0.5% ropivacaine). The rats received continuous intrathecal injection of corresponding drugs at 8.3 μL/h for 24 h via an implanted intrathecal catheter followed by 24 h-pause of injection for the ropivacaine group 2, the ropivacaine group 4 and the control group, 6 h-pause of injection for the ropivacaine group 1 and the ropivacaine group 3. For each group, the observation of behavioral change and the paw withdrawal mechanical threshold (PWMT) was conducted immediately after the injection and again after the pause of injection. After the PWMT observation, the rats were dissected to acquire L₃ spinal cords. Illumina sequencing was applied to construct gene libraries. Then the statistical methods were used to find out differentially expressed genes between the groups. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were conducted for those genes. Real-time RT-PCR was used to determine different expressions of some of those genes. RESULTS: Compared with control group, the PWMT got higher in the ropivacaine group 1-4 and was positively correlated with concentration, negatively correlated with discontinuation duration. Compared with control group, the ropivacaine group 1 had 488 differentially expressed genes, of which 456 were up-regulated and 32 were down-regulated; the ropivacaine group 2 had 1 194 differentially expressed genes, of which 1 092 were up-regulated and 102 were down-regulated; the ropivacaine group 3 had 518 differentially expressed genes, of which 384 were up-regulated and 134 were down-regulated; and the ropivacaine group 4 had 68 differentially expressed genes, of which 46 were up-regulated and 22 were down-regulated. GO enrichment analysis and KEGG signaling pathway analysis showed that most of these differentially expressed genes were related to signaling pathways of inflammatory response. CONCLUSIONS After intrathecal injection of 0.5% ropivacaine and 1.0% ropivacaine for 24 h, the differentially expressed genes in L₃ spinal cord of rats are mainly related to signaling pathways of inflammatory response.
Animals ; Genomics ; Injections, Spinal ; Male ; Rats ; Rats, Sprague-Dawley ; Ropivacaine ; Spinal Cord/metabolism*

Apoptosis ; Bone Neoplasms/drug therapy* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Matrix Metalloproteinase 2 ; Osteosarcoma ; Ropivacaine/pharmacology*

To investigate the effect of SB203580, a p38MAPK specific inhibitor, on ropivacaine-induced cytotoxicity in PC12 cells.
 Methods: PC12 cells were divided into three groups: the normal group (Group N), cells were cultured for 48 h; the ropivacaine group (Group R), cells were cultured with 15 mmol/L ropivacaine hydrochloride for 48 h; the ropivacaine+SB203580 group (Group R+S), cells were cultured with 15 mmol/L ropivacaine hydrochloride plus 10 μmol/L SB203580 for 48 h. The cell survival rates were detected by MTT assay. The protein levels of cleaved caspase-3, phosphor-p38 (p-p38) and cystolic cytochrome C (Cyt C) were detected by Western blotting.
 Results: Compared with the Group N, the number and survival rate of PC12 cells in the Group R and the Group R+S were significantly reduced (all P<0.05); the number and survival rate of PC12 cells in the Group R+S were significantly higher than those in the Group R (both P<0.05). Compared with the Group N, the levels of p-p38 and cleaved caspase-3, and the content of cytoplasmic Cyt C in the PC12 cells from the Group R and the Group R+S were significantly enhanced (all P<0.05); compared with the Group R, the levels of p-p38 and cleaved caspase-3, and the content of cytoplasmic Cyt C in the PC12 cells from the Group R+S were decreased (all P<0.05).
 Conclusion: The ropivacaine-induced cytotoxicity can be attenuated via inhibition of p38MAPK; which is related to decrease in Cyt C content and cleaved caspase-3 expression.
Anesthetics, Local ; toxicity ; Animals ; Apoptosis ; Imidazoles ; PC12 Cells ; Pyridines ; Rats ; Ropivacaine ; toxicity ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVE: To explore the effect of local infiltration of ropivacaine combined with multimodal analgesia with parecoxib for perioperative pain management in patients undergoing pancreaticoduodenectomy. METHODS: This randomized controlled trial was conducted among 98 patients undergoing pancreaticoduodenectomy in the Department of Biliary Surgery of West China Hospital between March, 2017 and August, 2018. The patients were randomized to receive perioperative analgesia with local infiltration anesthesia with ropivacaine combined with multimodal analgesia with parecoxib (experimental group, =50) or postoperative analgesia with dizosin (control group, =48). The regimens for intraoperative anesthesia and postoperative pain relief were identical in the two groups. The differences in NRS pain score, use of pain relief agents, the incidences of adverse reactions to analgesia and wound infection, and the time to first ambulation and first flatus passage after the operation were compared between the two groups. RESULTS: At 12, 24 h, 48 h, 72 h and 7 days after the operation, the patients in the experimental group had significantly lower NRS scores ( < 0.05) than those in the control group. The rate of use of rescue analgesics was significantly lower in the experimental group than in the control group (32% 66.67%, < 0.05); the rate of tramadol hydrochloride use was also significantly lower in the experimental group ( < 0.05). Compared with those in the control group, the patients in the experimental group showed a significantly lower total incidence of adverse reactions (22% 54.17%, < 0.05) as well as a lower incidence of nausea and vomiting ( < 0.05), an earlier time of first ambulation and first flatus passage after the operation ( < 0.05), and a shorter postoperative hospital stay ( < 0.05). CONCLUSIONS In patients undergoing pancreaticoduodenectomy, local infiltration of ropivacaine combined with multimodal analgesia with ropivacaine can effectively relieve perioperative pain, reduce the use of relief analgesics, lower the incidence of adverse reactions, and promote the recovery after the surgery.
Analgesia, Patient-Controlled ; Analgesics, Opioid ; Anesthetics, Local ; China ; Double-Blind Method ; Humans ; Isoxazoles ; Pain Management ; Pain Measurement ; Pain, Postoperative ; Pancreaticoduodenectomy ; Ropivacaine

OBJECTIVE: To evaluate the effect of dexmedetomidine combined with ropivacaine on brachial plexus block in patients scheduled for elective shoulder arthroscopy. METHODS: Ninety patients with American Society of Anesthesiologists (ASA) I or II, scheduled for elective shoulder arthroscopy, were randomly divided into three groups. In group R (n=30), the patients were given 10 mL of 0.375% ropivacaine in branchial plexus block (interscalene approach guided by ultrasound), in group D1 (n=30), the patients were given 10 mL of 0.375% ropivacaine (interscalene approach guided by ultrasound) + dexmedetomidine 0.2 μg/(kg×h) (intravenous pump infusion), and in group D2 (n=30), the patients were given 10 mL of 0.375% ropivacaine (interscalene approach guided by ultrasound) + dexedetomidine 0.7 μg/(kg×h) (intravenous pump infusion). To evaluate the effect of brachial plexus block before general anesthesia. Group D1 and group D2 were given dexmedetomidine intravenously for 1.0 μg/kg during 10 min, then the drug was pumped by 0.2 μg/(kg×h) and 0.7 μg/(kg×h) respectively until 30 min before the operation finished. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and before anesthesia (T0), 10 min (T1), 30 min (T2) after giving dexmedetomidine, discontinue medication (T3), after operation (T4), and extubation (T5) were investigated. Motor and sensory block onset times, block durations, and duration of analgesia were recorded. The scores of pain after operation and the adverse effects of shiver, hypopiesia, drowsiness, and blood loss were recorded during operation. RESULTS: Compared with group R, the duration of analgesia and duration of sensory block in group D1 and group D2 were significant longer (P<0.01), there was no significant difference between groups D1 and D2 (P>0.05). Compared with group R, at each time point of T1-T5, the heart rate and systolic blood pressure in group D1 and group D2 were significantly decreased (P<0.01). Compared with D1 group, the incidence of hypotension and bradycardia in group D2 were significantly different (P<0.05). CONCLUSION Intravenous dexmedetomidine could prolong the duration of analgesia time and sensory block within the brachial plexus block, inhibiting the stress response during arthroscopic shoulder surgery. Compared with high-dose, low-dose can provide safer and better clinical effect and reduce the adverse effects of dexmedetomidine.
Analgesics, Non-Narcotic ; Anesthetics, Local/therapeutic use* ; Arthroscopy ; Brachial Plexus ; Brachial Plexus Block ; Dexmedetomidine/therapeutic use* ; Double-Blind Method ; Humans ; Hypnotics and Sedatives/pharmacology* ; Prospective Studies ; Ropivacaine/therapeutic use* ; Shoulder Joint/surgery*

OBJECTIVE: To investigate effect and safty evaluation of stellate ganglion catheter retention with discontinuous block on sudden deafness. METHOD: One hundred and twenty-six patiens with sudden monaural deafness were randomly divided into Catheterp and block and control groups with 42 cases in each group. All patients' throats were given conventional blood activating drugs, hormone and hyperbaric oxygen therapy. stellate ganglion puncture retained catheter were administrated to the patients in catheter group followed by ropivacaine block 1 times/day, block group stellate ganglion puncture and ropivacaine block 1 times/day. The patients in control group were only received routine comprehensive treatment. Patients in both catheter group and block groups were treated by hyperbaric oxygen therapy after the block treatment. Curative effects of three groups were observed. The patients' satisfaction, heart rate, the chages of blood pressure before and after the block, detachment of tubes, and adverse drug reaction were recorded. RESULT: The effect of the treatment in both catheter group, block group was better than in control group (85.7%, 37 cases); 83.3%, 35 cases) vs 64.3%, 27 cases, P < 0.05). The satisfactory rate in the patients in catheter group was significantly higher than block group (83.3%, 35 cases vs 61.9%, 26 cases, P < 0.05). The heart rate and the blood pressure before and 5 minutes after catheterization in catheter group and block groupwere changed obviously. Moreover, no adverse drug reaction and detachment of tubes were observed. CONCLUSION It is a safe and effective administration of stellate ganglion catheter retention with interrupted ropivacaine block.
Amides ; therapeutic use ; Autonomic Nerve Block ; methods ; Blood Pressure ; Catheterization ; Catheters ; Hearing Loss, Sudden ; surgery ; Heart Rate ; Humans ; Hyperbaric Oxygenation ; Ropivacaine ; Stellate Ganglion ; surgery

OBJECTIVE: To investigate the effect of pretreatment with neurotrophin-3 (NT-3) on intrathecal ropivacaine in rats. METHODS: A total of 144 male Sprague Dawley rats weighing 280-320 g were successfully implanted with microspinal cather following the improved methods of Yaksh. The rats were randomly divided into 4 groups and given saline (Group NS, n=36), 0.5% ropivacaine (Group M, n=36), 1% ropivacaine (Group R, n=36), and ropivacaine+NT-3 (Group T, n=36). The rats received 0.12 mL/ kg body weight of ropivacaine at 0.5% or 1%, or normal saline only, via an implanted intrathecal catheter at 90-min interval for 12 h in Group NS, M, R and T. In the meantime the rats also received NT-3 0.1 mg/kg in group T. On days 1, 3, 5, 7, 14 and 28, we assessed the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL), behavioural change and histopathological damage score changed for possible neuronal injury within the spinal cord. RESULTS: Compared with Group NS and Group M, the PWMT and PWTL were significantly higher on 1, 3, 5 d and the histopathological damage score was significantly higher on 1, 3, 5, 7, 14 d in Group R (P<0.05). Compared with Group T, the PWMT and PWTL in Group R were significantly higher on 1, 3, 5 d and histopathological damage score was significantly higher on 5, 7, 14 d (P<0.05). CONCLUSION NT-3 pretreatment in mice has obvious protective effect against repeated intrathecal injection of 1% ropivacaine in the spinal nerve.
Amides ; adverse effects ; Animals ; Injections, Spinal ; Male ; Neurotrophin 3 ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Ropivacaine ; Spinal Cord ; drug effects

OBJECTIVE: To observe the influence of ropivacaine on the proliferation and migration of rat bone marrow mesenchymal stem cells (BMSCs) and provide basis for the clinical application of BMSCs. METHODS: Rat BMSCs were isolated and cultured by adherence method. Surface markers of BMSCs were examined by flow cytometry. Multipotent differentiation of BMSCs was detected by induced adipogenesis, osteogenesis and muscular differentiation. Proliferation of BMSCs was examined by CCK-8 and Brdu incorporation after ropivacaine treatment at different concentrations. Migration of BMSCs was tested by cell scratch assay and Millicell experiment. RESULTS: Cultured cells had representative appearance and surface markers of BMSC, and they had potential multiple differentiation. Ropivacaine treatment at 50 and 100 μmol/L significantly reduced the proliferation rate of BMSCs and Brdu incorporation rate. There was significant difference compared with the control group (P<0.05). Cellular scratch assay and migration experiment indicated that ropivacaine significantly reduced the migration of BMSCs. There was significant difference compared with the control group (P<0.05). All these mentioned effects of ropivacaine on BMSCs were dose-dependent. There was significant difference between groups (P<0.05). CONCLUSION Ropivacaine can significantly reduce the proliferation and migration of rat BMSCs, suggesting that the influence of local anesthetics on BMSCs has to be taken into account when BMSCs are used in clinical practice.
Amides ; pharmacology ; Animals ; Bone Marrow Cells ; Cell Differentiation ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Flow Cytometry ; Mesenchymal Stem Cells ; cytology ; drug effects ; Rats ; Ropivacaine

OBJECTIVE: To investigate the behavioral and ultrastructural changes of intrathecal administration of different concentrations of ropivacaine for 12 h. METHODS: Thirty male SD rats were randomly divided into 5 groups (6 rats in each group):group N (control), group A (ropivacaine 0.25%), group B (ropivacaine 0.5%), group C (ropivacaine 0.75%),and group D (ropivacaine 1.0%). A polyurethane microcatheter was inserted into the lumbar subarachnoid space 8 cm according to Yakshos intrathecal administration. The rats in group N received saline 0.12 mL/kg for 8 times at 1.5 h interval through the catheter, and the rats in the other groups received different concentrations of ropivacaine in the same way as in group N. The poster paw withdrawal latency to heat (PWHL) and mechanical stimulation (von Fray filament) (PWML) were measured the day before the intrathecal administration and 12 hours after the first intrathecal administration of ropivacaine. Motor function (MF) was measured after the last intrathecal administration. After the behavior test, the rats were sacrificed and the lumber segments of the spinal cord were immediately removed for electron microscopic examination. RESULTS: A total hind limb paralysis was seen at 30 seconds and intramuscular strain gradually came back 10~60 minutes after the intrathecal administration of ropivacaine in group A, B, C, and D, but not in group N. The recovery time of motor block of group A was the shortest (P<0.05), that of group D was the longest,and that of group B and C was between group A and D. Intrathecal administration of different concentrations of ropivacaine did not affect the percent maximum possible effect (%MPE) of PWHL and PWML. Electron microscopic examination showed that the spinal cords were normal in group N and A, slight edema of mitochondria and endoplasmic reticulum (ER) in group B, loosened fibrous layers in medullary sheath, edema and local degeneration of neuraxis in group C,and shrinkage of nuclear membrane, serious edema of ER, vacuolus change of mitochondria and local demyelination in group D. CONCLUSION Ropivacaine (0.5%, 0.75%, and 1.0%) administered intrathecally for 12 hours causes different degrees of ultrastructural changes in the spinal cord depending on concentrations.
Amides ; administration & dosage ; toxicity ; Anesthetics, Local ; administration & dosage ; toxicity ; Animals ; Behavior, Animal ; drug effects ; Dose-Response Relationship, Drug ; Injections, Spinal ; Male ; Microscopy, Electron ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ropivacaine ; Spinal Cord ; ultrastructure

OBJECTIVE: To explore the alterations of serum of myelin basic protein (MBP) concentration in the plasma and ultrastructure in the spinal cord after continuous intrathecal injection of different ropivacaine concentrations in rats. METHODS: Ninety-six male Sprague-Dawley rats weighing 220 to approximately 280 g were randomly divided into a control group (Group N), Group R(1), R(2) and R(3) (24 rats in each group). Each group was subdivided into 4 subgroups (6 rats in each subgroup). According to the method of Yaksh's, a polyurethane microspinal catheter was inserted into the lumbar subarachnoid space in which 8 cm segment was left. Rats in each group were continuously received 40 microL of intrathecal injection of normal saline(Group N), 0.5%, 0.75%, and 1.0% ropivacaine (Group R(1),R(2),R(3)), 3 times every 1.5 hours. Blood (0.5 mL) was drawn from the femoral artery to determine serum concentrations of MBP at the detecting time T(0)(before inserted pipe)and T(1)(before the first intrathecal injection); for the subgroups, the examining time was at T(2), T(3), T(4) and T(5)(6, 12, 24 and 48 h respectively after the last time intrathecal administration). After blood was drawn, the rats in each subgroups were decapitated and the spinal cord of L(1-2) intumescentia lumbalis were immediately removed for electronic microscopic examination. RESULTS: MBP levels were comparatively steady in Group N, R(1) and R(2), while there was statistical difference between Group R(3) and Group N, R(1),R(2),and R(3) (P<0.05). MBP level of Group R(3) was significantly higher at T(2),T(3),T(4) and T(5) than that at T(0)(P<0.01). The ultrastructural changes of the spinal cord in Group R(3) were pycnosis of most neurons, dilation of most rough endoplasmic reticulum, and vague structure of mitochondria and endocytoplasmic reticulum. A few neurons were completely de-generated losing the normal structure, with vacuole degeneration of crista mitochondriales or even partial loss. CONCLUSION The spinal cord ultrastructure is selectively vulnerable after intrathecal 1.0% ropivacaine injection, which may be one of the important pathophysiological bases for local anesthetic neurotoxicity. MBP may serve as a sensitive and specific indicator of spinal cord damage after intra-thecal administration of ropivacaine.
Amides ; administration & dosage ; pharmacology ; Anesthetics, Local ; administration & dosage ; pharmacology ; Animals ; Injections, Spinal ; methods ; Male ; Myelin Basic Protein ; Nerve Tissue Proteins ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ropivacaine ; Spinal Cord ; ultrastructure ; Transcription Factors ; blood