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1.
Int J Med Sci ; 18(5): 1096-1103, 2021.
Article in English | MEDLINE | ID: mdl-33526968

ABSTRACT

Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined. Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1. Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % ∙ sec-1 at T0 and 3.59 [2.58-3.51] % ∙ sec-1 at T1, P <0.001), but not in older group (2.61 [2.21-3.20] % ∙ sec-1 at T0, 2.63 [1.90-3.60] % ∙ sec-1 at T1, P = 0.949). Conclusions: General anesthesia could improve StO2 through increase of microvascular reactivity and decrease of tissue metabolism. However, microvascular reactivity to capillary recruitment under general anesthesia significantly improves in younger patients, not in older patients.


Subject(s)
Anesthesia, General/adverse effects , Elective Surgical Procedures/adverse effects , Microcirculation/drug effects , Oxygen Consumption/drug effects , Pain, Procedural/prevention & control , Adult , Age Factors , Aged , Aging/physiology , Anesthesia, General/methods , Female , Humans , Male , Microcirculation/physiology , Middle Aged , Oxygen/analysis , Oxygen/metabolism , Oxygen Consumption/physiology , Pain, Procedural/etiology , Propofol/administration & dosage , Propofol/adverse effects , Prospective Studies , Remifentanil/administration & dosage , Remifentanil/adverse effects , Spectroscopy, Near-Infrared
2.
Med Sci Monit ; 26: e926395, 2020 Nov 03.
Article in English | MEDLINE | ID: mdl-33139690

ABSTRACT

BACKGROUND The purpose of this study was to investigate the effects of sevoflurane on cancer immunosurveillance and metastasis in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS NCI-H23 cells, a human NSCLC cell line, were incubated with or without sevoflurane at the concentrations of 0, 12.5, 25, 50, 100, and 200 µM for 6 h. Cell viability, the expression of natural killer group 2, member D ligands (NKG2D ligands: UL16-binding proteins 1-3 [ULBP1-3] and major histocompatibility complex class I chain-related molecules A/B [MICA/B]), the expression of matrix metalloproteinases (MMPs), NK cell-mediated cytotoxicity, and cancer cell migration were measured. RESULTS At 12.5, 25, 50, and 100 µM, sevoflurane increased the expression of NKG2D ligands (ULBP2-3 and MICA, ULBP1-3, ULBP1-3, and ULBP1, respectively). Sevoflurane decreased the expression of NKG2D ligands at 200 µM (MICA/B). NK cell-mediated lysis of NCI-H23 cells at 200 µM sevoflurane was significantly reduced compared with the control (P=0.025; target cell: effect cell=1: 10). Sevoflurane increased the expression of MMP-1, -2, and -9 and increased cell migration in NCI-H23 cells at 50, 100, and 200 µM (P=0.001, 0.035, and 0.039, respectively, compared with the control after 18 h of wound formation). CONCLUSIONS Sevoflurane could suppress NKG2D-mediated NK cell cytotoxicity and increased expression of MMPs and migration in NCI-H23 cells. Further research is needed to determine the effects of sevoflurane on cancer immunosurveillance and metastasis in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/immunology , Immunity/drug effects , Lung Neoplasms/immunology , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Sevoflurane/pharmacology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Cell Survival/genetics , Cytotoxicity, Immunologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Ligands , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Wound Healing/drug effects
3.
Int J Med Sci ; 15(7): 723-729, 2018.
Article in English | MEDLINE | ID: mdl-29910677

ABSTRACT

Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis.


Subject(s)
Anesthetics, Intravenous/pharmacology , Osteogenesis/drug effects , Osteoprotegerin/metabolism , Propofol/pharmacology , RANK Ligand/metabolism , Animals , Bone Remodeling , Cell Differentiation , Glycoproteins , Mice , Osteoblasts , Osteoclasts , Osteoprotegerin/drug effects , RANK Ligand/drug effects
4.
Int J Med Sci ; 12(8): 644-9, 2015.
Article in English | MEDLINE | ID: mdl-26283884

ABSTRACT

OBJECTIVES: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. METHODS: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. RESULTS: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). CONCLUSION: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required.


Subject(s)
Analgesia/methods , Ketorolac/administration & dosage , Nefopam/administration & dosage , Oxycodone/administration & dosage , Pain, Postoperative/drug therapy , Adolescent , Adult , Aged , Analgesia, Patient-Controlled , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Opioid/administration & dosage , Double-Blind Method , Female , Gynecologic Surgical Procedures , Humans , Middle Aged , Myoma/surgery , Ovarian Neoplasms/surgery , Prospective Studies , Young Adult
5.
Paediatr Anaesth ; 25(7): 698-704, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25684223

ABSTRACT

BACKGROUND: Numerous studies have investigated the best method of selecting the appropriate size of endotracheal tube (ETT) for children. However, none of the methods or formulae for selection of ETT size have shown better prediction over another, and they have required complex formulae calculation or even use of cumbersome equipment. Recursive partitioning analysis creates a decision tree that is more likely to enable clearer and easier visualization of decision charts compared to other data mining methods. OBJECTIVES: The aim of the current study was to develop a clinically practical and intuitive chart for prediction of ETT size. METHODS: Pediatric patients aged 2-9 years undergoing general anesthesia were intubated with uncuffed ETT. The tube size was considered optimal when a tracheal leak was detected at an inflation pressure between 10 and 25 cmH2 O. The observed ETT size was compared with the predicted ETT size calculated using Cole's formula, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree structure analysis. Preference among the prediction methods was also investigated by asking physicians about their preference of methods. RESULTS: Correct prediction rates were 33.3%, 50%, 61.9%, and 59.5%, and close prediction rates were 61.9%, 83.3%, 88.1%, and 93.7% for Cole's formulae, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree model, respectively. Fourteen of 16 physicians prefer to use the easy-to-interpret tree model. CONCLUSIONS: Analysis of the tree model by recursive partitioning structure analysis accomplished a high correct and close prediction rate for selection of an appropriate ETT size. The intuitive and easy-to-interpret tree model would be a quick and helpful tool for selection of an ETT tube for pediatric patients.


Subject(s)
Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/statistics & numerical data , Trachea/diagnostic imaging , Anesthesia, General , Child , Child, Preschool , Equipment Design , Female , Humans , Male , Ultrasonography
6.
J Anesth ; 29(2): 292-4, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25238681

ABSTRACT

A 54-year-old woman with a history of severe tracheal stenosis caused by papillary thyroid cancer with tracheal invasion was admitted for an elective surgery. A bilateral superficial cervical plexus block with 0.5 % ropivacaine 14 ml (7 ml per side) under dexmedetomidine sedation was performed, followed by tracheal dissection and endotracheal tube (ETT) insertion. The patient continued spontaneous respiration without any hypoxic event, and the bispectral index was maintained at a range of 50-80. After ETT insertion, a total thyroidectomy and tracheal resection with end-to-end anastomosis were performed under general anesthesia. The patient was transferred to the surgical intensive care unit after extubation, and she recovered without any complications.


Subject(s)
Airway Management/methods , Cervical Plexus , Dexmedetomidine , Hypnotics and Sedatives , Nerve Block/methods , Tracheal Stenosis/complications , Carcinoma, Papillary/complications , Carcinoma, Papillary/pathology , Consciousness Monitors , Female , Humans , Intubation, Intratracheal , Middle Aged , Thyroid Neoplasms/complications , Thyroid Neoplasms/pathology , Thyroidectomy
7.
Int J Med Sci ; 11(7): 658-62, 2014.
Article in English | MEDLINE | ID: mdl-24843313

ABSTRACT

OBJECTIVES: Oxycodone is semi-synthetic opioid, oral and parenteral preparations have been widely used for acute and chronic pain. The aim of this study was to assess the efficacy and side effects of oxycodone and fentanyl in patient controlled analgesia (PCA) after laparoscopic cholecystectomy. METHODS: A prospective, randomized, double-blind study was conducted. 81 patients were randomly divided into two groups; fentanyl (10 mcg fentanyl and 1.5 mg ketorolac) and oxycodone group (1 mg oxycodone and 1.5 mg ketorolac). After the operation, a blinded observer assessed pain using a numerical rating scale (NRS), infused PCA dose, side effects, sedation levels, and satisfaction. RESULTS: Cumulative PCA dose of oxycodone group at 48 h (31.4 ± 16.0 ml) was significantly less than that of fentanyl group (43.8 ± 23.1 ml, P = 0.009). Oxycodone group showed more nausea at 6-24 h after the operation (P = 0.001), but there was no difference in satisfaction score (P = 0.073). There were no significant differences in other side effects, sedation and NRS scores between two groups. CONCLUSION: Oxycodone showed comparable effects for pain relief compared to fentanyl in spite of less cumulative PCA dose. Based on these results, we could conclude that oxycodone may be useful as an alternative to fentanyl for PCA after laparoscopic cholecystectomy.


Subject(s)
Analgesia, Patient-Controlled , Fentanyl/administration & dosage , Oxycodone/administration & dosage , Pain, Postoperative/drug therapy , Adult , Aged , Cholecystectomy , Female , Humans , Ketorolac/administration & dosage , Laparoscopy , Male , Middle Aged , Pain Management , Pain, Postoperative/pathology
9.
Anesth Analg ; 116(3): 685-93, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23400991

ABSTRACT

BACKGROUND: The incidence and predictive factors for chronic pain after breast cancer surgery have been widely studied. Because it negatively affects patients' daily lives, methods to prevent and reduce chronic pain and its severity should be developed. Our previous study showed that propofol anesthesia has an antihyperalgesic effect under remifentanil-induced hyperalgesia and reduced acute pain compared with sevoflurane anesthesia. In this study, we investigated the hypothesis that propofol would prevent the development and severity of chronic pain after breast cancer surgery, as in acute pain. METHODS: A retrospective study was conducted with 175 women (n = 86 in the propofol group and n = 89 in the sevoflurane group) aged 20 to 65 years who underwent breast cancer surgery between March 2007 and December 2008. Patients were followed up by telephone in July 2011. Analysis included incidence, severity, and duration of chronic pain between propofol and sevoflurane groups. Severity was categorized into mild, moderate, and severe pain. Duration of chronic pain was also divided into 3 categories by 1-year time interval. Risk factors associated with the incidence and severity of chronic pain after breast cancer surgery were also identified. RESULTS: Chronic pain after breast cancer surgery was more likely to occur in the sevoflurane group compared with the propofol group (95% confidence interval [CI] 1.146-1.809, P = 0.007). Among patients with chronic pain, neither the severity (95% CI 0.516-7.419) nor duration (95% CI 0.106-1.007) differed between patients receiving sevoflurane and propofol. Younger age (95% CI 0.907-0.992, P = 0.021), axillary lymph node dissection (95% CI 1.204-1.898, P = 0.003), 24-hour postoperative morphine consumption (95% CI 1.004-1.116, P = 0.036), and sevoflurane (95% CI 1.146-1.809, P = 0.007) were predictive factors for the development of chronic pain. Higher 24-hour postoperative morphine consumption (95% CI 1.001-1.379, P = 0.049) increased the severity of chronic pain. CONCLUSIONS: This study showed that propofol anesthesia was associated with a lower incidence of chronic pain after breast cancer surgery than sevoflurane anesthesia. However, propofol did not have a significant effect on severity and duration of chronic pain. Further prospective studies are needed to confirm the validity of these provocative findings.


Subject(s)
Anesthetics/administration & dosage , Breast Neoplasms/surgery , Chronic Pain/drug therapy , Methyl Ethers/administration & dosage , Pain, Postoperative/drug therapy , Propofol/administration & dosage , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Chronic Pain/epidemiology , Female , Humans , Middle Aged , Pain, Postoperative/epidemiology , Retrospective Studies , Sevoflurane , Surveys and Questionnaires , Treatment Outcome , Young Adult
10.
J Anesth ; 27(6): 868-73, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23982855

ABSTRACT

PURPOSE: This prospective, double-blind, placebo-controlled study was designed to determine the efficacy of nitrous oxide (N(2)O) in alleviating the pain that followed sequential injection of propofol and rocuronium. METHODS: A total of 205 adult patients (age, 18-68 years) received one of the following combinations: NaCl and 100 % O(2) (group C); 0.5 mg/kg lidocaine and 100 % O(2) (group L); NaCl and a mixture of 67 % N(2)O/O(2) (group N); or 0.5 mg/kg lidocaine and a mixture of 67 % N(2)O/O(2) (group LN). Vein occlusion was released after 1 min, and 5 ml propofol was injected over 10 s. Pain was evaluated on a visually enlarged, laminated, numeric rating (0-10) scale. The remainder of the induction dose of propofol (with a 3-ml bolus of normal saline and 0.6 mg/kg rocuronium) was then injected. The response to the rocuronium injection was assessed with a four-point scale (0-3). RESULTS: The incidence and severity of pain from the propofol injection in groups L, N, and LN were significantly lower than those in group C (P < 0.001). Frequency and intensity of the withdrawal response were significantly less in groups N and LN than in groups C and L (no response, P < 0.001; severe response, P < 0.001). CONCLUSIONS: Pretreatment with inhaled N(2)O can reduce the pain associated with propofol and rocuronium injection. Moreover, N(2)O (with or without lidocaine) is more effective than lidocaine alone in reducing rocuronium-related withdrawal reactions associated with sequential injection of propofol and rocuronium.


Subject(s)
Androstanols/adverse effects , Nitrous Oxide/administration & dosage , Pain/drug therapy , Propofol/adverse effects , Administration, Inhalation , Adult , Androstanols/administration & dosage , Double-Blind Method , Female , Humans , Injections , Male , Middle Aged , Pain/etiology , Pain Measurement/methods , Propofol/administration & dosage , Prospective Studies , Rocuronium
11.
Cell Mol Neurobiol ; 32(6): 971-7, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22198556

ABSTRACT

Neuropathic pain concurrent with mood disorder from peripheral nerve injury is a serious clinical problem that significantly affects quality of life. Recent studies have suggested that a lack of brain-derived neurotrophic factor (BDNF) in the limbic system may cause this pain-emotion. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but the role of 4-MC-induced BDNF in pain-emotion is poorly understood. Thus, we assessed the possible involvement of BDNF in brain in depression-like behavior during chronic pain following peripheral nerve injury. In addition, we examined whether intracerebroventricular (i.c.v.) 4-MC prevents chronic pain in rats and produces an antidepressant effect. Sprague-Dawley rats implanted intracerebroventricularly with a PE-10 tube were subjected to chronic constriction injury (CCI). Pain was assessed by a reduction in paw withdrawal latency (PWL) to heat stimuli after CCI. We also used a forced swimming testing (FST; time of immobility, in seconds) from day 14 to day 21 after CCI. Modulation of pain and emotional behavior was performed by injection of PD0325901 (a MEK1/2 inhibitor). 4-MC (100 nM) was continuously administered i.c.v. for 3 days during the period from day 14 to day 21 after CCI. To block analgesic and antidepressant effects, anti-BDNF antibody or K252a (a TrkB receptor inhibitor) was injected in combination with 4-MC. Naloxone was also coadministered to confirm the analgesic effect of 4-MC. During the chronic stage after CCI, the rats showed a sustained decrease in PWL (thermal hyperalgesia) associated with extension of the time of immobility (depression-like behavior). PD0325901 significantly reduced the decrease in PWL and the increased time of immobility after CCI. The decreased PWL and increased time of immobility were also reduced by 4-MC and by treatment with an ERK1/2 inhibitor. These effects of 4-MC i.c.v. were reversed by anti-BDNF and K252a. The analgesic effect of 4-MC i.c.v. was also antagonized by naloxone. Based on these results, we suggest that a lack of BDNF and activation of ERK1/2 in the pain-emotion network in the CNS may be involved in depression-like behavior during chronic pain. 4-MC i.c.v. ameliorates chronic pain and depression-like behavior by producing of BDNF and normalization of ERK1/2 activation. Therefore, enhancement of BDNF may be a new treatment strategy for chronic pain associated with depression.


Subject(s)
Behavior, Animal , Brain-Derived Neurotrophic Factor/metabolism , Catechols/administration & dosage , Catechols/therapeutic use , Chronic Pain/complications , Chronic Pain/drug therapy , Depression/drug therapy , Analgesics/administration & dosage , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Behavior, Animal/drug effects , Benzamides/pharmacology , Catechols/pharmacology , Depression/complications , Diphenylamine/analogs & derivatives , Diphenylamine/pharmacology , Injections, Intraventricular , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Restraint, Physical
12.
J Anesth ; 26(6): 910-3, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22797902

ABSTRACT

We report a case of a patient with a double-primary aortoenteric fistula with an abdominal aortic aneurysm. A 75-year-old man was taken to the operating room for the repair of an abdominal aortic aneurysm and a suspected aortoenteric fistula between the aorta and sigmoid colon. Sudden onset of massive bleeding through the nasogastric tube occurred after the induction of anesthesia. Surgical exploration confirmed an unexpected aortoduodenal fistula. Primary aortoenteric fistula is extremely rare and difficult to diagnose, and may cause fatal bleeding. The possibility of the presence of aortoenteric fistula, including multiple types, should be considered in the anesthetic management of abdominal aortic aneurysm.


Subject(s)
Anesthesia , Aorta, Abdominal , Aortic Diseases/complications , Intestinal Fistula/complications , Intraoperative Complications/etiology , Vascular Fistula/complications , Aged , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/surgery , Aortic Diseases/therapy , Duodenal Diseases/complications , Duodenal Diseases/therapy , Humans , Intestinal Fistula/therapy , Intraoperative Complications/therapy , Male , Patient Care Planning , Sigmoid Diseases/complications , Sigmoid Diseases/therapy , Tomography, X-Ray Computed , Vascular Fistula/therapy
13.
J Pain Res ; 15: 229-239, 2022.
Article in English | MEDLINE | ID: mdl-35125890

ABSTRACT

BACKGROUND: The present study aimed to develop a rat model for mechanical allodynia after traumatic brain injury (TBI) and to investigate the expression of brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) using this model. METHODS: A total of 180 rats were randomly allocated into three groups: a control group (group C), a sham-operated group (group S), and a controlled cortical impact induced TBI group (group T), 60 in each group. Von Frey test was performed to evaluate mechanical withdrawal thresholds. An enzyme-linked immunosorbent assay was performed to quantify BDNF level in CSF. RESULTS: The 50% withdrawal thresholds of group T were lower than those of group C and group S at all measuring points except for the preoperative period (P = 0.026, <0.001, and <0.001 for POD1, POD7, and POD14, respectively). The BDNF level of group T was higher than those of group C and group S at POD1 (P = 0.005). CONCLUSION: Upregulation of the BDNF expression in CSF was observed in rats who developed mechanical allodynia on the day after TBI. Based on our findings, to elucidate the relationship between TBI-induced neuropathic pain and BDNF expression in CSF, further research should be carried out through a multifaceted approach to a broad spectrum of pain behavior models.

14.
Front Pharmacol ; 13: 842779, 2022.
Article in English | MEDLINE | ID: mdl-35250589

ABSTRACT

Background: Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts cancer survivors' quality of life and is challenging to treat with existing drugs for neuropathic pain. TNF-α is known to potentiate TRPV1 activity, which contributes to CIPN. Here, we assessed the role of TMI-1, a TNF-α-converting enzyme inhibitor, in paclitaxel (PAC)-induced neurotoxicity in dorsal root ganglion (DRG) cells. Materials and Methods: Immortalized DRG neuronal 50B11 cells were cultured and treated with PAC or PAC with TMI-1 following neuronal differentiation. Cell viability, analysis of neurite growth, immunofluorescence, calcium flow cytometry, western blotting, quantitative RT-PCR, and cytokine quantitation by ELISA were performed to determine the role of TMI-1 in neurotoxicity in neuronal cells. Results: PAC administration decreased the length of neurites and upregulated the expression of TRPV1 in 50B11 cells. TMI-1 administration showed a protective effect by suppressing inflammatory signaling, and secretion of TNF-α. Conclusion: TMI-1 partially protects against paclitaxel-induced neurotoxicity by reversing the upregulation of TRPV1 and decreasing levels of inflammatory cytokines, including TNF-α, IL-1ß, and IL-6 in neuronal cells.

15.
J Anesth ; 24(2): 182-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20127371

ABSTRACT

PURPOSE: Various strategies have been studied to reduce the discomfort of rocuronium injection. This study was designed to determine the effect-site target concentration (Ce) of remifentanil at which there was a 50% probability of preventing movement from pain in response to the injection of rocuronium (EC(50)). METHODS: Anesthesia was induced with a propofol target-controlled infusion (TCI, Marsh model) and remifentanil TCI (Minto model). Effect-site target concentration of propofol was 3 microg/ml. Ce of remifentanil for the first patient started at 2.0 ng/ml. Ce of remifentanil for each subsequent patient was determined by the response of the previous patient by the Dixon up-and-down method with an interval of 0.5 ng/ml. After both drugs reached target concentration, rocuronium 0.8 mg/kg was administered, and the pain response was observed. RESULTS: The EC(50) of remifentanil was 1.5 +/- 0.45 ng/ml by Dixon's up-and-down method. From probit analysis, the EC(50) of remifentanil was 1.37 ng/ml (95% confidence limits, 0.69-2.15 ng/ml), and the EC(95) was 3.19 ng/ml (95% confidence limits, 2.31-11.24 ng/ml). CONCLUSION: The EC(50) of remifentanil to blunt the withdrawal responses to rocuronium injection was 1.37-1.5 ng/ml during 3 microg/ml propofol TCI anesthesia.


Subject(s)
Androstanols/administration & dosage , Hypnotics and Sedatives/pharmacokinetics , Movement/drug effects , Neuromuscular Nondepolarizing Agents/administration & dosage , Piperidines/pharmacokinetics , Reflex/drug effects , Adolescent , Adult , Aged , Androstanols/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Hypnotics and Sedatives/pharmacology , Male , Middle Aged , Movement/physiology , Neuromuscular Nondepolarizing Agents/adverse effects , Pain/chemically induced , Pain/prevention & control , Piperidines/pharmacology , Reflex/physiology , Remifentanil , Rocuronium , Young Adult
16.
Mol Neurobiol ; 56(11): 7408-7419, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31037647

ABSTRACT

Chemotherapy-induced peripheral neuropathy (CIPN) adversely impacts quality of life and a challenge to treat with existing drugs used for neuropathic pain. Losartan, an angiotensin II type 1 receptor (AT1R) antagonist widely used to treat hypertension, has been reported to have analgesic effects in several pain models. In this study, we assessed losartan's analgesic effect on paclitaxel-induced neuropathic pain (PINP) in rats and its mechanism of action in dorsal root ganglion (DRG). Rats received intraperitoneal injections of 2 mg/kg paclitaxel on days 0, 2, 4, and 6 and received single or multiple intraperitoneal injections of losartan potassium dissolved in phosphate-buffered saline at various times. The mechanical thresholds, protein levels of inflammatory cytokines, and cellular location of AT1R and interleukin 1ß (IL-1ß) in the DRG were assessed with behavioral testing, Western blotting, and immunohistochemistry, respectively. Data were analyzed by two-way repeated-measures analysis of variance for the behavioral test or the Mann-Whitney U test for the Western blot analysis and immunohistochemistry. Single and multiple injections of losartan ameliorated PINP, and losartan delayed the development of PINP. Paclitaxel significantly increased, and losartan subsequently decreased, the expression levels of inflammatory cytokines, including IL-1ß and tumor necrosis factor α (TNF-α), in the lumbar DRG. AT1R and IL-1ß were expressed in both neurons and satellite cells and losartan decreased the intensity of IL-1ß in the DRG. Losartan ameliorates PINP by decreasing inflammatory cytokines including IL-1ß and TNF-α in the DRG. Our findings provide a new or add-on therapy for CIPN patients.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Cytokines/metabolism , Ganglia, Spinal/metabolism , Hyperalgesia/drug therapy , Inflammation Mediators/metabolism , Losartan/therapeutic use , Neuralgia/chemically induced , Neuralgia/drug therapy , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Disease Models, Animal , Ganglia, Spinal/drug effects , Glial Fibrillary Acidic Protein/metabolism , Hyperalgesia/complications , Hyperalgesia/pathology , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/therapeutic use , Losartan/pharmacology , Male , NF-kappa B/metabolism , Neuralgia/complications , Neurons/drug effects , Neurons/metabolism , Paclitaxel/adverse effects , Phosphorylation/drug effects , Rats, Sprague-Dawley
17.
Korean J Pain ; 32(3): 223-227, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31257831

ABSTRACT

Radiofrequency neurolysis (RFN) of the genicular nerves has recently become accepted as an effective technique to alleviate knee pain particularly in patients with knee osteoarthritis (OA) or postoperative pain. However, genicular nerve RFN can produce high procedure and equipment costs, longer procedural times, procedure-related pain, and failure rate of over 25%. We are presenting two cases of alcohol neurolysis of the genicular nerve using fluoroscopy and ultrasonography in patients with knee OA or persistent postsurgical pain of the knee. Alcohol neurolysis of the genicular nerve with dual imaging modality can be a cheap, safe and effective method in patients with chronic knee pain.

18.
Medicine (Baltimore) ; 97(35): e12187, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30170468

ABSTRACT

BACKGROUND: Midazolam premedication is widely used before general anesthesia, but lacks clinical evidence of effectiveness. The present study aimed to evaluate the effectiveness of midazolam premedication following 4 aspects: anxiety reduction, sedation, hemodynamic stabilization, and analgesia. METHODS: In a randomized, single-blind, prospective study, a total of 128 women were allocated to the midazolam premedication group (Group P, n = 64) or the control group (Group N, n = 64). The patients were asked to complete the Beck anxiety inventory (BAI) 2 times: on the day before surgery (BS) and 30 minutes after midazolam premedication (T0). Depth of anesthesia using state entropy (SE), conventional hemodynamic data using heart rate (HR) and mean blood pressure (MBP), and analgesic profiles using surgical pleth index (SPI) were acquired at the following 4 points: T1-pre-induction, T2-prior to intubation, T3-intubation, and T4-20 minutes after intubation. RESULTS: No change in BAI score was observed between BS and T0 in both groups P and N (median and interquartile range [IQR], Group P: BS-4.5 [2.0-7.0], T0-4.0 [1.0-9.0], P = .603; Group N: BS-4.0 [1.0-8.5], T0-3.5 [1.0-6.0], P = .066). Midazolam premedication reduced SE at T2-4 (mean difference with 95% confidence interval [95% CI], T2-7.1 [1.6-12.6], P = .012; T3-10.4 [6.5-14.4], P < .001; T4-9.2 [5.0-13.4], P < .001). Midazolam premedication also reduced HR (mean differences [95% CI], T1-7.3 [2.5-12.1], P = .003; T3-6.6 [1.1-12.2], P = .020) and MBP at T1 and T3 (mean differences [95% CI], T1-7.3 [2.5-12.1], P = .003; T3-8.6 [1.3-15.9], P = .021), and lowered SPI at T1-3 (mean differences [95% CI]: T1-12.7 [6.1-19.4], P < .001; T2-6.0 [0.5-11.5], P = .033; T3-7.9 [1.7-14.1], P = .012). CONCLUSION: Midazolam premedication did not reduce the level of anxiety. However, midazolam premedication reduced the entropy values, stabilized hemodynamics, and provided analgesia during the induction of anesthesia. The purpose of midazolam premedication needs to be reconsidered.


Subject(s)
Analgesia/methods , Anxiety/prevention & control , Hemodynamics/drug effects , Hypnotics and Sedatives/therapeutic use , Midazolam/therapeutic use , Preanesthetic Medication/methods , Adult , Aged , Female , Humans , Middle Aged , Prospective Studies , Single-Blind Method , Treatment Outcome , Young Adult
19.
Pain Physician ; 20(4): 261-269, 2017 05.
Article in English | MEDLINE | ID: mdl-28535549

ABSTRACT

BACKGROUND: Epidurally administered dexamethasone might reduce postoperative pain. However, the effect of epidural administration of dexamethasone on postoperative epidural analgesia in major abdominal surgery has been doubtful. OBJECTIVES: To investigate the effects and optimal dose of epidural dexamethasone on pain after major abdominal surgery. STUDY DESIGN: A prospective randomized, double-blind study. SETTING: University hospital. METHODS: One hundred twenty ASA physical status I and II men, scheduled for gastrectomy, were enrolled. Patients were randomly assigned to receive one of 3 treatment regimens (n = 40 in each group): dexamethasone 5 mg (1 mL) with normal saline (1 mL) (group D) or dexamethasone 10 mg (2 mL) (group E) or 2 mL of normal saline (group C) mixed with 8 mL of 0.375% ropivacaine as a loading dose. After the surgery, 0.2% ropivacaine - fentanyl 4 ?g/mL was epidurally administered for analgesia. The infusion was set to deliver 4 mL/hr of the PCEA solution, with a bolus of 2 mL per demand and 15 minutes lockout time. The infused volume of PCEA, intensity of postoperative pain using visual analogue scale (VAS) during rest and coughing, incidence of postoperative nausea and vomiting (PONV), usage of rescue analgesia and rescue antiemetic, and side effects such as respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, and 48 hours after the end of surgery. RESULTS: The resting and effort VAS was significantly lower in group E compared to group C at every time point through the study period. On the contrary, only the resting VAS in group D was lower at 2 hours and 6 hours after surgery. Total fentanyl consumption of group E was significantly lower compared to other groups. There was no difference in adverse effect such as hypotension, bradycardia, PONV, pruritis, and urinary retention among groups. LIMITATIONS: Use of epidural PCA with basal rate might interrupt an accurate comparison of dexamethasone effect. Hyperglycemia and adrenal suppression were not evaluated. CONCLUSIONS: Epidural dexamethasone was effective for reducing postoperative pain. Especially, an epidural dexamethasone dose of 10 mg was more effective than a lower dose in patients undergoing gastrectomy which was associated with moderate to severe postoperative pain.


Subject(s)
Analgesics/therapeutic use , Dexamethasone/therapeutic use , Pain, Postoperative/drug therapy , Aged , Amides/administration & dosage , Analgesia, Epidural/adverse effects , Analgesics/administration & dosage , Anesthetics, Local/administration & dosage , Dexamethasone/administration & dosage , Double-Blind Method , Female , Gastrectomy , Humans , Male , Middle Aged , Pain Measurement , Prospective Studies , Ropivacaine
20.
Korean J Anesthesiol ; 70(3): 356-360, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28580089

ABSTRACT

Anesthetic experience in frontotemporal dementia (FTD) with severe hypotension associated autonomic dysfunction has not yet been reported. Here in case, we report on the case of treatment with vasopressin to refractory hypotension in FTD patient. A 54-year-old male presented with a ten-year history of FTD with frequent syncope. The patient was scheduled to undergo subtotal gastrectomy for resection of stomach cancer. During the operation, sudden hypotension occurred and it was refractory to fluid and 1 unit of blood resuscitation and did not respond to catecholamine. Transesophageal echocardiography showed normal heart with adequate volume state. After intravenous administration of arginine vasopressin, the patient's vital signs returned to baseline values. Arginine vasopressin might be considered as a valuable alternative for treatment of severe refractory hypotension in autonomic dysfunction patients with FTD.

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