Sunyeul Lee

Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model

Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli.

Growth Differentiation Factor 15 Expression in Astrocytes After Excitotoxic Lesion in the Mouse Hippocampus

Growth differentiation factor 15 (GDF15) is, a member of the transforming growth factor β (TGF-β) superfamily of proteins. Although GDF15 is well established as a potent neurotrophic factor for neurons, little is known about its role in glial cells under neuropathological conditions. We monitored GDF15 expression in astrocyte activation after a kainic acid (KA)-induced neurodegeneration in the ICR mice hippocampus. In control, GDF15 immunoreactivity (IR) was evident in the neuronal layer of the hippocampus; however, GDF15 expression had increased in activated astrocytes throughout the hippocampal region at day 3 after the treatment with KA. LPS treatment in astrocytes dramatically increased GDF15 expression in primary astrocytes. In addition, LPS treatment resulted in the decrease of the IκB-α degradation and increase of the phosphorylation level of RelA/p65. These results indicate that GDF15 has a potential link to NF-κB activation, making GDF15 a valuable target for modulating inflammatory conditions.

Vomiting after a pediatric adenotonsillectomy: comparison between propofol induced sevoflurane-nitrous oxide maintained anesthesia and TIVA with propofol-remifentanil

Background Anesthesia methods and drugs affect postoperative nausea and vomiting. Propofol is known to have antiemetic effects. We compared the incidence of postoperative vomiting (POV) in children undergoing an adenotonsillectomy; anesthesia in one group was induced with propofol and maintained with sevoflurane and nitrous oxide, and the other group received total intravenous anesthesia (TIVA) with propofol-remifentanil. Methods Ninety children, ASA physical status I, were assigned randomly to one of two groups. In the PSN group, anesthesia was maintained with 2-3 vol% sevoflurane and 50% nitrous oxide. In the PR group, anesthesia was maintained with 10 mg/kg/h propofol and 0.25 µg/kg/min remifentanil. In both groups, anesthesia was induced with 0.5 µg/kg remifentanil and 2 mg/kg propofol. The incidence of POV and the need for rescue antiemetics were assessed in the postanesthesia care unit at 6, 12, and 24 hours postoperatively. Results The total incidence of POV was not significantly different between the groups; POV occurred in eight (17.7%) and three (6.7%) children in the PSN and PR groups, respectively. Postoperative frequency of retching in the recovery room was significantly higher in the PSN group, with four children (8.9%) in the PSN group compared to none (0%) in the PR group (P = 0.041). The frequency of POV 24 hrs after exiting the recovery room tended to be higher in the PSN group than the PR group, but no statistically significant difference was observed. Conclusions If the development of POV in the early anesthetic recovery phase of children undergoing adenotonsillectomy is adequately prevented, propofol-induced anesthesia maintained with sevoflurane-nitrous oxide is as safe as TIVA with propofol-remifentanil.

Expression of granulocyte colony-stimulating factor 3 receptor in the spinal dorsal horn following spinal nerve ligation-induced neuropathic pain

In previous studies that have profiled gene expression in patients with complex regional pain syndrome (CRPS), the expression of granulocyte colony-stimulating factor 3 receptor (G-CSFR) was elevated, as were a number of pain-associated genes. The present study determined the expression of G-CSFR and the mechanisms by which it may affect hypersensitivity, focusing on the signal transducer and activator of transcription 3 (STAT3)/transient receptor potential cation channel subfamily V 1 (TRPV1) signaling pathway in particular, which is an important mediator of pain. Following L5 spinal nerve ligation (SNL) surgery, the protein and mRNA levels of G-CSFR increased in the ipsilateral spinal dorsal horn when compared with the sham and/or contralateral control. Double immunofluorescence further demonstrated that G-CSFR colocalized with TRPV1 and phosphorylated STAT in the neurons of the spinal dorsal horn. G-CSF treatment led to an increase in G-CSFR and TRPV1 expression and phosphorylation of STAT3. These results indicate that G-CSF-induced G-CSFR expression may activate TRPV1 by promoting phosphorylation of STAT3. Collectively, the results suggest, for the first time, that the expression of G-CSFR in neurons following peripheral nerve injury may be involved in the induction and maintenance of neuropathic pain through the STAT3 and TRPV1 signaling pathway.

Effects of nicardipine on the onset time and intubation conditions of rocuronium-induced neuromuscular blockade

STUDY OBJECTIVE The objective of this study was to identify the effects of nicardipine on neuromuscular blockade of rocuronium, such as the onset time and intubation conditions, using a nicardipine dose that attenuates cardiovascular responses during endotracheal intubation. DESIGN Randomized, double-blinded, placebo-controlled clinical comparison was used as the design of this study SETTING The study was conducted at the operating room of a university hospital. PATIENTS Participants of this study comprise 78 American Society of Anesthesiologists physical status 1 and 2 patients, aged 18 to 60 years who were undergoing elective surgery under general anesthesia. INTERVENTIONS The nicardipine group was given an intravenous bolus of 20 μg/kg nicardipine before tracheal intubation: the control group was given an intravenous bolus of a comparable volume of normal saline before tracheal intubation. MEASUREMENTS Using a TOF-Watch SX monitor, the time from the end of the injection of rocuronium to maximum depression of T1 (onset time) was measured. Intubation was performed 1 minute after rocuronium administration, and the status of the intubation conditions was assessed. The mean blood pressure and heart rate were each measured after endotracheal intubation. Rate pressure product values were also calculated. MAIN RESULTS Intubation conditions were clinically acceptable in 37 (94.9%) of 39 patients in group N compared with 29 (74.4%) of 39 in group C (P < .05). The onset time of rocuronium was significantly faster in group N than in group C (P < .05). The mean blood pressure was significantly lower in group N than in group C (P < .05). The heart rate was significantly higher in group N than in group C (P < .05). Rate pressure product values showed no significant difference between the two groups (P > .05). CONCLUSIONS Pretreatment with 20 μg/kg nicardipine improves intubation conditions, shortens the onset time of rocuronium, and attenuates cardiovascular responses to tracheal intubation.

TWIK-Related Spinal Cord K+ Channel Expression Is Increased in the Spinal Dorsal Horn after Spinal Nerve Ligation

Purpose The TWIK-related spinal cord K+ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. Materials and Methods We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). Results The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. Conclusion TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.

Treatment with Epidural Blood Patch for Iatrogenic Intracranial Hypotension after Spine Surgery

Intracranial hypotension syndrome typically occurs spontaneously or iatrogenically. It can be associated with headache, drowsy mentality and intracranial heamorrhage. Iatrogenic intracranial hypotension can occur due to dural pucture, trauma and spine surgery. Treatment may include conservative therapy and operation. We report a case of a 54-year-old man who was successfully treated with epidural blood patches for intracranial hypotension due to cerebrospinal fluid (CSF) leakage into the lumbosacral area after spine surgery.

Bone regeneration with umbilical cord blood mesenchymal stem cells in femoral defects of ovariectomized rats

Objectives Current treatments for osteoporosis were prevention of progression, yet it has been questionable in the stimulation of bone growth. The mesenchymal stem cells (MSCs) treatment for osteoporosis aims to induce differentiation of bone progenitor cells into bone-forming osteoblasts. We investigate whether human umbilical cord blood (hUCB)-MSCs transplantation may induce bone regeneration for osteoporotic rat model induced by ovariectomy. Methods The ovariectomized (OVX) group (n = 10) and OVX-MSCs group (n = 10) underwent bilateral ovariectomy to induce osteoporosis, while the Sham group (n = 10) underwent sham operation at aged 12 weeks. After a femoral defect was made at 9 months, Sham group and OVX group were injected with Hartmann solution, while the OVX-MSCs group was injected with Hartmann solution containing 1 × 107 hUCB-MSCs. The volume of regenerated bone was evaluated using micro-computed tomography at 4 and 8 weeks postoperation. Results At 4- and 8-week postoperation, the OVX group (5.0% ± 1.5%; 6.1% ± 0.7%) had a significantly lower regenerated bone volume than the Sham group (8.6% ± 1.3%; 12.0% ± 1.8%, P < 0.01), respectively. However, there was no significant difference between the OVX-MSCs and Sham groups. The OVX-MSCs group resulted in about 53% and 65% significantly higher new bone formation than the OVX group (7.7% ± 1.9%; 10.0% ± 2.9%, P < 0.05). Conclusions hUCB-MSCs in bone defects may enhance bone regeneration in osteoporotic rat model similar to nonosteoporotic bone regeneration. hUCB-MSCs may be a promising alternative stem cell therapy for osteoporosis.

Effect of an epinephrine mixture for interscalene block on hemodynamic changes after the beach chair position under general anesthesia: a retrospective study

Background The beach chair position (BCP) can cause significant hypotension. Epinephrine is used to prolong the duration of local anesthetics; it is also absorbed into blood and can exert systemic effects. This study determined the effects of epinephrine mixed with ropivacaine for an interscalene block (ISB) on hemodynamic changes related to BCP. Methods Patient data collected from March 2013 to August 2014 were used retrospectively. We divided the patients into three groups: 1) ISB only, 2) I+G (general anesthesia after ISB without epinephrine), and 3) I+E+G (general anesthesia after ISB with epinephrine). Mean blood pressure (MBP) and heart rate (HR) were measured for 30 minutes at 5-minute intervals. Results The study analyzed data from 431 patients. MBP tended to decrease gradually in the groups I+G and I+E+G. There were significant differences in MBP between the groups I+G and I, and between the groups I+G and I+E+G. Group I+E+G showed a significant increase in HR compared with the other two groups. Conclusions ISB with an epinephrine mixture did not prevent hypotension caused by the BCP after general anesthesia. HR increased only in response to the epinephrine mixture. A well-planned prospective study is required to compare hemodynamic changes in that context.

Improvement of the reception capability of time dissemination of shortwave broadcasting by digital modulation

KRISS (Korea Research Institute of Standards and Science) has been operating the standard time and frequency broadcasting station (call sign: HLA) since 1984. The station HLA broadcasts continuous time and frequency signals on 5 MHz carrier frequency and 2 kW transmit power. But the poor reception due to radio interference is decreasing users. Therefore to increase the radio reception, a digital modulation method and an increase of bit rate are introduced additionally to the present amplitude-modulated radio signal. We describe a digital modulation method for improving radio reception of the standard time and frequency by shortwave.