Won Hyung Lee

Effects of intraoperative low dose ketamine on remifentanil-induced hyperalgesia in gynecologic surgery with sevoflurane anesthesia

Background Remifentanil is useful during general anesthesia because of its rapid onset and short acting time. However, some studies report that due to opioid-induced hyperalgesia (OIH) and tolerance, remifentanil also increases early postoperative pain. The occurrence of OIH and opioid-induced tolerance is mainly thought to be due to central sensitization by the activation of NMDA receptors. Therefore, we investigated the effects of continuous infusion of ketamine, an NMDA receptor antagonist, on postoperative pain and the quantity of opioids used. Methods 40 patients scheduled to undergo laparoscopic gynecologic surgery were randomly allocated into two groups. Anesthesia was equally maintained with sevoflurane and 4 ng/ml of remifentanil in all patients. Ketamine (0.3 mg/kg) was injected and followed with a continuous dosage of 3 µl/kg/min in the ketamine group (n = 20) while the control group was injected and infused with an equal amount of normal saline. We compared postoperative VAS up to 7 hours and morphine demand through PCA. Results Postoperative VAS and morphine demand was significantly lower in the ketamine group 2 and 3 hours after surgery, respectively. Conclusions When general anesthesia is maintained with sevoflurane and remifentanil in patients undergoing laparoscopic gynecologic surgery, continuous infusion of low dose ketamine decreased early postoperative pain and the quantity of opioids used.

The effects of paracetamol, ketorolac, and paracetamol plus morphine on pain control after thyroidectomy.

Background The aim of this study was to compare the efficacy of ketorolac, paracetamol, and paracetamol plus morphine on pain relief after thyroidectomy. Methods Eighty patients were randomly allocated to one of the 4 groups: normal saline (group C), ketorolac 30 mg (group K), paracetamol 1 g (group P), and paracetamol 700 mg plus morphine 3 mg (group PM). Each regimen was administered intravenously (IV) 30 min. before the end of surgery. If pain was not relieved, patients received an IV bolus of pethidine hydrochloride 25 mg. Pain intensity using a visual analogue scale (VAS) was recorded at 0.5, 1, 2, 4, and 6 hr after the end of surgery. Results VAS at 0.5 and 1 hr after the end of surgery were significantly lower in group K, group P, and group PM than in group C (P < 0.05). The number of patients receiving pethidine hydrochloride at 0.5 and 1 hr after the end of surgery was significantly lower in group K, group P, and group PM than in group C (P < 0.05). There was no significant difference among the groups in the incidences of adverse events associated with study medications and patient satisfaction (P > 0.05). Conclusions Paracetamol 1 g IV possesses a similar analgesic efficacy to ketorolac 30 mg IV after thyroidectomy. Paracetamol may represent an alternative to ketorolac for pain prevention after mildly to moderately painful surgery in situations where the use of NSAIDs is unsuitable.

Antinociceptive Effects of Intraperitoneal and Intrathecal Vitamin E in the Rat Formalin Test

Background Vitamin E is widely known to be one of the reactive oxygen species (ROS) scavengers and a drug that can easily be obtained, and it has been shown to attenuate the pain responses induced by various causes in animal pain models. Thus, this experiment was conducted to assess the antinociceptive effects of vitamin E by comparing intraperitoneal and intrathecal injections in rats subjected to the formalin test. Methods After the intraperitoneal and intrathecal injections of vitamin E were carried out, respectively (IP: 500 mg/kg, 1 g/kg, and 2 g/kg, IT: 3 mg/kg, 10 mg/kg, and 30 mg/kg), the formalin test was perfumed. As soon as 5% formalin was injected into left hind paw, the number of flinches induced by pain was measured at 5-minute intervals for 1 hour. Results Formalin injected into the left hind paw induced biphasic nociceptive behavior in all animals. Intraperitoneal injection of vitamin E diminished the nociceptive behavior in a dose-dependent manner during the early and late phase. Intrathecal vitamin E diminished nociceptive behavior dose dependently during the late phase but showed no significant difference in the early phase. Conclusions Vitamin E attenuated acute nociception when it was injected systemically, while both systemic and intrathecal injection produced analgesia in a rat model of formalin-induced hyperalgesia.

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.

Genome-wide expression profiling of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a chronic, progressive, and devastating pain syndrome characterized by spontaneous pain, hyperalgesia, allodynia, altered skin temperature, and motor dysfunction. Although previous gene expression profiling studies have been conducted in animal pain models, there genome-wide expression profiling in the whole blood of CRPS patients has not been reported yet. Here, we successfully identified certain pain-related genes through genome-wide expression profiling in the blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and p<0.05). Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of major histocompatibility complex class I A subtype (HLA-A29.1), matrix metalloproteinase 9 (MMP9), alanine aminopeptidase N (ANPEP), l-histidine decarboxylase (HDC), granulocyte colony-stimulating factor 3 receptor (G-CSF3R), and signal transducer and activator of transcription 3 (STAT3) genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We focused on the MMP9 gene that, by qRT-PCR, showed a statistically significant difference in expression in CRPS patients compared to controls with the highest relative fold change (4.0±1.23 times and p = 1.4×10−4). The up-regulation of MMP9 gene in the blood may be related to the pain progression in CRPS patients. Our findings, which offer a valuable contribution to the understanding of the differential gene expression in CRPS may help in the understanding of the pathophysiology of CRPS pain progression.

Effect of a small dose of propofol or ketamine to prevent coughing and laryngospasm in children awakening from general anesthesia

Background Coughing during emergence from general anesthesia may be detrimental in children. We compared the effect of a small dose of propofol or ketamine administered at the end of sevoflurane anesthesia on the incidence or severity of coughing in children undergoing a minimal invasive operation. Methods One hundred and eighteen children aged between 3 and 15 years, American Society of Anesthesiologists (ASA) status I, were enrolled in this randomized double blind study. Anesthesia was induced with propofol or ketamine and maintained with sevoflurane in N2O/O2. Each group received propofol 0.25 mg/kg or ketamine 0.25 mg/kg and the control group received saline 0.1 ml/kg. The decision to perform tracheal extubation was based on specified criteria, including the resumption of spontaneous respiration. During emergence from anesthesia and extubation, coughing was observed and graded at predefined times. Results The incidence of emergence without coughing was higher in the propofol group than in the ketamine and control group (19%, 11% and 6%, respectively), whereas the incidence of severe coughing was higher in the control group than in propofol and ketamine group (17.14%, 10.0% and 6.98%, respectively). Conclusions The addition of propofol 0.25 mg/kg decreased the incidence of coughing after sevoflurane general anesthesia in children undergoing non-painful procedures.

Antinociceptive effect of phenyl N-tert-butylnitrone, a free radical scavenger, on the rat formalin test

Background Reactive oxygen species (ROS) such as superoxide radicals, hydrogen peroxide, nitric oxide, and nitroperoxide, cause oxidative stress which interferes with normal cell functioning, resulting in cell damage. It is reported to be associated with chronic pain, especially neuropathic pain, and inflammatory pain. ROS is also closely related to central sensitization. Therefore, this study was designed to explore the effects of Phenyl N-tert-butylnitrone (PBN), an ROS scavenger, in acute, continuous, and increasing pain caused by central sensitization. Methods Male Sprague-Dawley rats were divided into 2 groups, an intraperitoneal group (IP) and an intrathecal group (IT), and once again divided into an experimental group and a control group. The experimental group was injected with Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, either intraperitoneally or intrathecally. After inducing pain by injecting formalin into the hind paw, pain behaviors were measured. Lumbar enlargement immmunohistochemistry was performed to assess nitrotyrosine, an oxidative stress marker, to identify the degree of protein nitration. Results Both experimental groups of IP and IT showed statistically significant decreases in the number of flinches compared to the control group in phase 1 and 2. Immunohistochemical evaluation in the control group revealed an increase in nitrated proteins in the gray matter of the lumbar spinal cord, but a significant decrease in nitrated proteins in the gray matter of lumbar spinal cord of the experimental group. Conclusions Intraperitoneal and intrathecal administration of PBN decreases analgesic behaviors, allowing us to believe that ROS is mainly responsible for acute pain and central sensitization.

Ultrasonographic Measurement of the Ligamentum Flavum Depth; Is It a Reliable Method to Distinguish True and False Loss of Resistance?

Background Previous studies have shown that if performed without radiographic guidance, the loss of resistance (LOR) technique can result in inaccurate needle placement in up to 30% of lumbar epidural blocks. To date, no study has shown the efficacy of measuring the depth of the posterior complex (ligamentum flavum, epidural space, and posterior dura) ultrasonographically to distinguish true and false LOR. Methods 40 cervical epidural blocks were performed using the LOR technique and confirmed by epidurograms. Transverse ultrasound images of the C6/7 area were taken before each cervical epidural block, and the distances from the skin to the posterior complex, transverse process, and supraspinous ligament were measured on each ultrasound view. The number of LOR attempts was counted, and the depth of each LOR was measured with a standard ruler. Correlation of false and true positive LOR depth with ultrasonographically measured depth was also statistically analyzed. Results 76.5% of all cases (26 out of 34) showed false positive LOR. Concordance correlation coefficients between the measured distances on ultrasound (skin to ligamentum flavum) and actual needle depth were 0.8285 on true LOR. Depth of the true positive LOR correlated with height and weight, with a mean of 5.64 ± 1.06 cm, while the mean depth of the false positive LOR was 4.08 ± 1.00 cm. Conclusions Ultrasonographic measurement of the ligamentum flavum depth (or posterior complex) preceding cervical epidural block is beneficial in excluding false LOR and increasing success rates of cervical epidural blocks.

Sevoflurane Exposure during the Critical Period Affects Synaptic Transmission and Mitochondrial Respiration but Not Long-term Behavior in Mice

Background: Anesthesia during the synaptogenic period induces dendritic spine formation, which may affect neurodevelopment. The authors, therefore, evaluated whether changes in synaptic transmission after dendritic spine formation induced by sevoflurane were associated with long-term behavioral changes. The effects of sevoflurane on mitochondrial function were also assessed to further understand the mechanism behind spinogenesis. Methods: Postnatal day 16 to 17 mice were exposed to sevoflurane (2.5% for 2 h), and synaptic transmission was measured in the medial prefrontal cortex 6 h or 5 days later. The expression of postsynaptic proteins and mitochondrial function were measured after anesthesia. Long-term behavioral changes were assessed in adult mice. Results: Sevoflurane increased the expression of excitatory postsynaptic proteins in male and female mice (n = 3 to 5 per group). Sevoflurane exposure in male mice transiently increased miniature excitatory postsynaptic current frequency (control: 8.53 ± 2.87; sevoflurane: 11.09 ± 2.58) but decreased miniature inhibitory postsynaptic current frequency (control: 10.18 ± 4.66; sevoflurane: 6.88 ± 2.15). Unexpectedly, sevoflurane increased miniature inhibitory postsynaptic current frequency (control: 1.81 ± 1.11; sevoflurane: 3.56 ± 1.74) in female mice (neurons, n = 10 to 21 per group). Sevoflurane also increased mitochondrial respiration in male mice (n = 5 to 8 per group). However, such changes from anesthesia during the critical period did not induce long-term behavioral consequences. Values are presented as mean ± SD. Conclusions: Sevoflurane exposure during the critical period induces mitochondrial hyperactivity and transient imbalance of excitatory/inhibitory synaptic transmission, without long-lasting behavioral consequences. Further studies are needed to confirm sexual differences and to define the role of mitochondrial activity during anesthesia-induced spine formation.

Glomus Tumor Causing Anterior Thigh Pain: A Case Report

Glomus tumors are a rare, benign neoplasm and 75% exist in the subungual region. Extradigital glomus tumors are much more difficult to diagnose because of their atypical location and symptoms. Furthermore, if their symptoms are similar to neuropathic pain, the patient can suffer from misdirected treatment due to misdiagnosis. It is essential to perform careful evaluation of the lesion itself in order to reduce misdiagnosis. Ultrasonography is a useful, non-invasive method that can be easily performed in the pain clinic for local evaluation and diagnosis. We report a case of misdiagnosed glomus tumor in the thigh which was properly diagnosed after ultrasonography.