OBJECTIVE: The purpose of this study was to determine whether xenon post-conditioning affects mTOR signaling as well as endoplasmic reticulum stress (ERS)-apoptosis pathway in rats with spinal cord ischemia/reperfusion injury. METHODS: Fifty male rats were randomized equally into sham-operated group (Sham group), I/R model group (I/R group), I/R model+ xenon post-conditioning group (Xe group), I/R model+rapamycin (a mTOR signaling pathway inhibitor) treatment group (I/R+ Rapa group), and I/R model + xenon post- conditioning with rapamycin treatment group (Xe + Rapa group).. In the latter 4 groups, SCIRI was induced by clamping the abdominal aorta for 85 min followed by reperfusion for 4 h. Rapamycin (or vehicle) was administered by daily intraperitoneal injection (4 mg/kg) for 3 days before SCIRI, and xenon post-conditioning by inhalation of 1∶1 mixture of xenon and oxygen for 1 h at 1 h after initiation of reperfusion; the rats without xenon post-conditioning were given inhalation of nitrogen and oxygen (1∶ 1). After the reperfusion, motor function and histopathologic changes in the rats were examined. Western blotting and real-time PCR were used to detect the protein and mRNA expressions of GRP78, ATF6, IRE1α, PERK, mTOR, p-mTOR, Bax, Bcl-2 and caspase-3 in the spinal cord. RESULTS: The rats showed significantly lowered hind limb motor function following SCIRI (P < 0.01) with a decreased count of normal neurons, increased mRNA and protein expressions of GRP78, ATF6, IRE1α, PERK, and caspase-3, and elevated p-mTOR/mTOR ratio and Bax/Bcl-2 ratio (P < 0.01). Xenon post-conditioning significantly decreased the mRNA and protein levels of GRP78, ATF6, IRE1α, PERK and caspase-3 (P < 0.05 or 0.01) and reduced p-mTOR/mTOR and Bax/Bcl-2 ratios (P < 0.01) in rats with SCIRI; the mRNA contents and protein levels of GRP78 and ATF6 were significantly decreased in I/R+Rapa group (P < 0.01). Compared with those in Xe group, the rats in I/R+Rapa group and Xe+Rapa had significantly lowered BBB and Tarlov scores of the hind legs (P < 0.01), and caspase-3 protein level and Bax/Bcl-2 ratio were significantly lowered in Xe+Rapa group (P < 0.05 or 0.01). CONCLUSION By inhibiting ERS and neuronal apoptosis, xenon post- conditioning may have protective effects against SCIRI in rats. The mTOR signaling pathway is partially involved in this process.
Animals ; Apoptosis ; Caspase 3/metabolism* ; Endoplasmic Reticulum Stress ; Endoribonucleases/pharmacology* ; Injections, Intraperitoneal ; Male ; Neurons/pathology* ; Nitrogen/metabolism* ; Oxygen/metabolism* ; Protein Serine-Threonine Kinases ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Sirolimus/pharmacology* ; Spinal Cord Ischemia/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Xenon/therapeutic use* ; bcl-2-Associated X Protein/metabolism*

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*

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.
Anesthesia ; Betacoronavirus ; isolation & purification ; Cesarean Section ; methods ; Coronavirus Infections ; complications ; Female ; Humans ; Infant ; Injections, Spinal ; Pandemics ; Pneumonia, Viral ; complications ; Pregnancy

Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.
Anesthesia ; Betacoronavirus ; Cesarean Section ; Coronavirus Infections ; complications ; surgery ; Female ; Humans ; Infant ; Injections, Spinal ; Pneumonia, Viral ; complications ; diagnosis ; surgery ; Pregnancy ; Pregnancy Complications, Infectious ; surgery ; Pregnancy Outcome ; Preoperative Care

BACKGROUND: Lumbosacral transforaminal epidural injection (TFEI) is an effective treatment for spinal disease. However, TFEI may have several types of complications, some of which can be attributed to intravascular injection. We reviewed studies to compare the intravascular injection rate among different needle types. METHODS: We searched the literature for articles on the intravascular injection rate among different needle types used in TFEI. The search was performed using PubMed, MEDLINE, the Cochrane Library, EMBASE, and Web of Science. RESULTS: A total of six studies comprising 2359 patients were identified. Compared with the Quincke needle, the Whitacre needle reduced the intravascular injection rate (OR = 0.57, 95% CI = [0.44–0.73], P < 0.001). However, compared with the Quincke needle, the Chiba needle did not reduce the intravascular injection rate (OR = 0.80, 95% CI = [0.44–1.45], P = 0.46). In one study, the intravascular injection rate using a blunt-tip needle was lower than that using a sharp needle. In another study, the Whitacre and the blunt-tip needle have similar intravascular injection rates, while, the catheter-extension needle showed a reduced intravascular injection rate. CONCLUSIONS: This meta-analysis showed that the Whitacre needle reduced the intravascular injection rate as compared with the Quincke needle, but failed to establish that the Chiba needle can decrease the intravascular injection rate in TFEI. Moreover, the blunt-tip needle can reduce the intravascular injection rate compared with the Quincke needle, and the catheter-extension needle can reduce the intravascular injection rate compared with the Whitacre and the blunt-tip needle.
Anesthesia, Epidural ; Humans ; Injections, Epidural ; Needles ; Spinal Diseases

BACKGROUND: Previous studies have shown that sequential intrathecal injection of fentanyl and hyperbaric bupivacaine for cesarean section (CS) anesthesia provides a superior anesthetic effect than use of bupivacaine alone, and prolongs postoperative analgesia. Herein, we investigated whether rapid intrathecal injection of fentanyl followed by slow injection of hyperbaric bupivacaine affects the duration of postoperative analgesia, the effectiveness of anesthesia, and hemodynamic status. METHODS: Fifty-six parturients with American Society of Anesthesiologists physical status I or II, aged 18–40 years, and scheduled to undergo elective CS were randomly assigned to 2 groups of 28 patients each. The normal sequential group received sequential intrathecal injections of fentanyl and hyperbaric bupivacaine at the same rate, each with a 5 ml syringe. The rapid sequential group received a rapid intrathecal injection of fentanyl with an insulin syringe, followed by a slow injection of hyperbaric bupivacaine with a 5 ml syringe. The onset of sensory block, the timing of the first rescue analgesia, the doses of rescue analgesics, the degree of postoperative pain, the onset and duration of motor block, the incidence and duration of hypotension, and spinal anesthesia-related complications were recorded. RESULTS: While both approaches had comparable spinal anesthesia-related complications, incidence and duration of hypotension, and doses of ephedrine, the rapid sequential group exhibited a more rapid onset of sensory block, a higher sensory level, and more prolonged postoperative analgesia. CONCLUSIONS: Rapid sequential injection of fentanyl and hyperbaric bupivacaine produced superior anesthesia and more prolonged postoperative analgesia than sequential injections of both at the same rate.
Analgesia ; Analgesics ; Anesthesia ; Anesthesia, Spinal ; Anesthetics ; Bupivacaine ; Cesarean Section ; Ephedrine ; Female ; Fentanyl ; Hemodynamics ; Humans ; Hypotension ; Incidence ; Injections, Spinal ; Insulin ; Pain, Postoperative ; Pregnancy ; Syringes

OBJECTIVE: This study evaluated the feasibility of ultrasound-guided lumbar nerve root block (LNRB) and S1 nerve root block by identifying spread patterns via fluoroscopy in cadavers.METHOD: A total of 48 ultrasound-guided injections were performed in 4 fresh cadavers from L1 to S1 roots. The target point of LNRB was the midpoint between the lower border of the transverse process and the facet joint at each level. The target point of S1 nerve root block was the S1 foramen, which can be visualized between the median sacral crest and the posterior superior iliac spine, below the L5-S1 facet joint. The injection was performed via an in-plane approach under real-time axial view ultrasound guidance. Fluoroscopic validation was performed after the injection of 2 cc of contrast agent.RESULTS: The needle placements were correct in all injections. Fluoroscopy confirmed an intra-foraminal contrast spreading pattern following 41 of the 48 injections (85.4%). The other 7 injections (14.6%) yielded typical neurograms, but also resulted in extra-foraminal patterns that occurred evenly in each nerve root, including S1.CONCLUSION: Ultrasound-guided injection may be an option for the delivery of injectate into the S1 nerve root, as well as lumbar nerve root area.
Cadaver ; Fluoroscopy ; Injections, Spinal ; Lumbosacral Region ; Methods ; Needles ; Spinal Nerve Roots ; Spine ; Ultrasonography ; Zygapophyseal Joint

BACKGROUND: Hypertonic saline (HS) injections for decompressive neuroplasty (DN) can cause pain. We assessed whether a continuous infusion of HS through an infusion pump would reduce injection-related pain compared with repeated bolus administrations. METHODS: Fifty patients scheduled for DN were randomized to either the bolus injection or the continuous infusion group. After appropriately placing the epidural catheter, 4 mL of 5% NaCl was injected as four boluses of 1 mL each at 15-minute intervals or infused over 1 hour using an infusion pump. The severity of pain induced by HS injection, as measured by the 11-point numerical rating scale (NRS), was the primary outcome. The severity of low back or lower extremity pain, as measured by the 11-point NRS and Oswestry Disability Index (ODI), 3 months following the procedure, was the secondary outcome. RESULTS: Data from 21 patients in the bolus group and 23 in the continuous infusion group were analyzed. No statistically significant difference in injection-related pain was identified between the two groups during the initial HS administration (P = 0.846). However, there was a statistically significant reduction in injection-related pain in the continuous infusion group compared to the bolus injection group from the second assessment onwards (P = 0.001, < 0.001, and < 0.001, respectively). No significant between-group differences in the NRS and ODI scores 3 months post-procedure were noted (P = 0.614 and 0.949, respectively). CONCLUSIONS: Our study suggests that administering HS through a continuous infusion is a useful modality for reducing HS injection-related pain during DN.
Catheters ; Chronic Pain ; Humans ; Infusion Pumps ; Injections, Epidural ; Low Back Pain ; Lower Extremity ; Radiculopathy ; Saline Solution, Hypertonic ; Spinal Stenosis

BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.
Animals ; Biochemistry ; Body Weight ; Bone Marrow ; Brain ; Cell- and Tissue-Based Therapy ; Culture Media ; DNA ; Friedreich Ataxia ; Heart ; Hematology ; Humans ; Injections, Spinal ; Mesenchymal Stromal Cells ; Methods ; Mice ; Neurodegenerative Diseases ; Neuroprotection ; Reference Values ; Severe Combined Immunodeficiency ; Spinal Cord

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
Animals ; Computational Biology ; Constriction ; Down-Regulation ; Hyperalgesia ; Inflammation ; Injections, Spinal ; Mice ; MicroRNAs ; Neuralgia ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Protein Kinases ; Rats ; Sciatic Nerve ; Spinal Cord ; Up-Regulation