Amiloride and benzamil showed antinocicepitve effects in several pain models through the inhibition of acid sensing ion channels (ASICs). However, their role in neuropathic pain has not been investigated. In this study, we investigated the effect of the intrathecal amiloride and benzamil in neuropathic pain model, and also examined the role of ASICs on modulation of neuropathic pain. Neuropathic pain was induced by L4-5 spinal nerve ligation in male Sprague-Dawley rats weighing 100-120 g, and intrathecal catheterization was performed for drug administration. The effects of amiloride and benzamil were measured by the paw-withdrawal threshold to a mechanical stimulus using the up and down method. The expression of ASICs in the spinal cord dorsal horn was also analyzed by RT-PCR. Intrathecal amiloride and benzamil significantly increased the paw withdrawal threshold in spinal nerve-ligated rats (87%+/-12% and 76%+/-14%, P=0.007 and 0.012 vs vehicle, respectively). Spinal nerve ligation increased the expression of ASIC3 in the spinal cord dorsal horn (P=0.01), and this increase was inhibited by both amiloride and benzamil (P<0.001 in both). In conclusion, intrathecal amiloride and benzamil display antinociceptive effects in the rat spinal nerve ligation model suggesting they may present an alternative pharmacological tool in the management of neuropathic pain at the spinal level.
Acid Sensing Ion Channels/genetics/metabolism ; Amiloride/*analogs & derivatives/pharmacology/*therapeutic use ; Analgesics/pharmacology/*therapeutic use ; Animals ; Disease Models, Animal ; Male ; Neuralgia/*drug therapy ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Spinal Cord/metabolism ; Transcription, Genetic/drug effects

BACKGROUND: There is increasing evidence that more aggressive pain management is needed in patients undergoing craniotomy in Korea. However, no consensus or standardized analgesic regimen has been established to date. To achieve this consensus, we undertook a survey of the current state of post-craniotomy pain management in Korea. METHODS: A postal questionnaire was sent to anesthesiologists, neurosurgeons and nurses of neurosurgical departments at 44 university hospitals in Korea. Of the 44 centers that were sent questionnaires, 35 centers returned these from their anesthesiology department resulting in a response rate of 73%, and 25 returned the questionnaires from their neurosurgery department (response rate: 57%). RESULTS: Fifty-three percent of neurosurgeons answered that current postoperative pain management was adequate after craniotomy, whereas only 8% of anesthesiologists agreed. However, 72% of neurosurgeons also agreed that a more aggressive pain management was needed for post-craniotomy patients. Fifty-two percent and 23% of neurosurgeons used non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen as a first-line analgesic, respectively. Twenty-five percent of neurosurgeons used opioids as a first-line analgesic. Fifty percent of anesthesiologists used strong opioids alone or with NSAIDs as a first-line analgesic. About 10% of both groups used weak opioids as a first-line drug. CONCLUSIONS: Many clinicians agree that post-craniotomy pain is not adequately managed and more aggressive strategies are needed. Nevertheless, opioid analgesics are still avoided because of the concern of side effects despite no evidence to suggest increased risk when use carefully.
Acetaminophen ; Analgesia ; Analgesics, Opioid ; Anesthesiology ; Anti-Inflammatory Agents, Non-Steroidal ; Consensus ; Craniotomy ; Hospitals, University ; Humans ; Korea ; Neurosurgery ; Pain Management ; Pain, Postoperative ; Surveys and Questionnaires

BACKGROUND: Postoperative sore throat (POST) is a common adverse event after general anesthesia. The aim of this study was to evaluate the effectiveness of 2% lidocaine jelly applied on the single-lumen endotracheal tube (ETT) and thermal softening of the ETT, and a combination of both interventions on the development of POST. METHODS: Patients (n = 144) undergoing general anesthesia were randomly assigned to one of four groups: Control group (un-softened ETT lubricated with saline); Lidocaine group (un-softened ETT lubricated with 2% lidocaine jelly); Softened group (thermally softened ETT lubricated with saline); and Combined group (thermally softened ETT lubricated with 2% lidocaine jelly). Sore throat was evaluated at 0, 1, 6, 24, and 48 h after extubation. The occurrence of any postoperative complication was also assessed including hoarseness and coughing. RESULTS: No significant difference was observed in the severity of POST at all time points. However, the incidences of POST for overall (0–48 h) and the immediately following period (0 h) were significantly lower in the Combined group (52.9% and 47.1%) than in the Control group (79.4% and 76.5%), Lidocaine group (81.8% and 78.8%), and Softened group (82.9% and 74.3%). The overall incidence of hoarseness did not differ among the groups. No other postoperative complication was observed in any of the patients. CONCLUSIONS: No differences were observed in the severity of POST. However, 2% lidocaine jelly applied on thermally softened ETT reduced the overall incidence of POST. Therefore, this combined intervention could be considered as an alleviating strategy for POST.
Anesthesia, General ; Cough ; Hoarseness ; Humans ; Incidence ; Lidocaine ; Pharyngitis ; Postoperative Complications

BACKGROUND: Endotracheal intubation usually causes transient hypertension and tachycardia. The cardiovascular and arousal responses to endotracheal and endobronchial intubation were determined during rapid-sequence induction of anesthesia in normotensive and hypertensive elderly patients. METHODS: Patients requiring endotracheal intubation with (HT, n = 30) or without hypertension (NT, n = 30) and those requiring endobronchial intubation with (HB, n = 30) or without hypertension (NB, n = 30) were included in the study. Anesthesia was induced with intravenous thiopental 5 mg/kg followed by succinylcholine 1.5 mg/kg. After intubation, all subjects received 2% sevoflurane in 50% nitrous oxide and oxygen. Mean arterial pressure (MAP), heart rate (HR), plasma catecholamine concentration, and Bispectral Index (BIS) values, were measured before and after intubation. RESULTS: The intubation significantly increased MAP, HR, BIS values and plasma catecholamine concentrations in all groups, the peak value of increases was comparable between endotracheal and endobronchial intubation. However, pressor response persisted longer in the HB group than in the HT group (5.1 +/- 1.6 vs. 3.2 +/- 0.9 min, P < 0.05). The magnitude of increases in MAP and norepinephrine from pre-intubation values was greater in the hypertensive than in the normotensive group (P < 0.05), while there were no differences in those of HR and BIS between the hypertensive and normotensive groups. CONCLUSIONS: Cardiovascular response and arousal response, as measured by BIS, were similar in endobronchial and endotracheal intubation groups regardless of the presence or absence of hypertension except for prolonged pressor response in the HB group. However, the hypertensive patients showed enhanced cardiovascular responses than the normotensive patients.
Aged ; Anesthesia ; Arousal ; Arterial Pressure ; Heart Rate ; Humans ; Hypertension ; Intubation ; Intubation, Intratracheal ; Methyl Ethers ; Nitrous Oxide ; Norepinephrine ; Oxygen ; Plasma ; Succinylcholine ; Tachycardia ; Thiopental

Background: This study was performed to evaluate the effect of a wagon as a transport vehicle instead of the standard stretcher car to reduce children’s anxiety of separation from parents. The secondary goal was to evaluate whether this anxiolytic effect was related to age. Methods: We divided 80 children (age 2–7 years) into two groups. The stretcher group was transferred to the operating room on a conventional stretcher car, whereas the wagon group was transferred using a wagon. The level of anxiety was evaluated three times using the Modified Yale Preoperative Anxiety Scale (mYPAS): in the waiting area (T0), in the hallway to the operating room (T1), and before induction of anesthesia (T2). Results: The mYPAS score was significantly lower in the wagon group (36.7 [31.7, 51.7]) than in the stretcher group (51.7 [36.7, 83.3]) at T1 (P = 0.007). However, there was no difference in the mYPAS score between the two groups at T2 (46.7 [32.5, 54.2] vs. 51.7 [36.7, 75.0], respectively, P = 0.057). The baseline anxiety tended to be lower with increasing age (r = −0.248, P = 0.031). During transportation to the operating room, the increase in the mYPAS score (T1-T0) was greater as the age of children decreased in the stretcher group (r = −0.340, P = 0.034). However, no correlation was observed in the wagon group (r = −0.053, P = 0.756). Conclusion The wagon method decreased preoperative anxiety, suggesting that it may be a good alternative for reducing preoperative anxiety in children.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague–Dawley rats (weight 150–180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

BACKGROUND: The beach chair position (BCP) is associated with hypotension that may lead to cerebral ischemia. Arginine vasopressin (AVP), a potent vasoconstrictor, has been shown to prevent hypotension in BCP. It also improves cerebral oxygenation in different animal models. The present study examined the effect of escalating doses of AVP on systemic hemodynamics and cerebral oxygenation during surgery in BCP under general anesthesia. METHODS: Sixty patients undergoing arthroscopic shoulder surgery in BCP under general anesthesia were randomly allocated to receive either saline (control, n = 15) or three different doses of AVP (0.025, 0.05, or 0.075 U/kg; n = 15 each) 2 minutes before BCP. Mean arterial pressure (MAP), heart rate (HR), regional cerebral oxygen saturation (SctO2), and jugular venous oxygen saturation (SjvO2) were measured after induction of anesthesia and before (presitting in supine position) and after BCP. RESULTS: AVP per se given before BCP increased MAP, and decreased SjvO2, SctO2, and HR in all patients (P < 0.05 for all). BCP decreased MAP, the magnitude of which and hence the incidence of hypotension was decreased by AVP in a dose-dependent manner. While in BCP, every dose of AVP reduced the HR and SctO2. Accordingly, it increased the incidence of cerebral desaturation (> 20% SctO2 decrease from the baseline value) with no differences in SjvO2 and the incidence of SjvO2 < 50% or SjvO2 < 40% among the groups. CONCLUSIONS: AVP ameliorates hypotension associated with BCP in a dose-dependent manner in patients undergoing shoulder surgery under general anesthesia. However, AVP may have negative effects on SctO2 before and after BCP and on SjvO2 before BCP.
Anesthesia ; Anesthesia, General* ; Arginine Vasopressin ; Arterial Pressure ; Brain Ischemia ; Heart Rate ; Hemodynamics ; Humans ; Hypotension* ; Incidence ; Models, Animal ; Oxygen ; Shoulder* ; Vasopressins*

BACKGROUND: Intravenously administered indocyanine green (ICG) may cause misreadings of cerebral oximetry and pulse oximetry in patients undergoing carotid endarterectomy under general anesthesia. The present study determined the effects of two different doses (12.5 mg vs. 25 mg) of ICG on regional cerebral tissue oxygen saturation (SctO2) and percutaneous peripheral oxygen saturation (SpO2). METHODS: Twenty-six patients receiving ICG for videoangiography were divided into two groups according to the dosage (12.5 mg and 25 mg, n = 13 in each group). Heart rate, arterial blood pressure, SctO2, and SpO2 were measured before and after an intravenous bolus administration of ICG. RESULTS: Following the dye administration, no changes in heart rate or arterial blood pressure were noted in either group. SctO2 was increased in both groups; however, the magnitude of the increase was greater (21.6 +/- 5.8% vs. 12.6 +/- 4.1%, P < 0.0001) and more prolonged (28.4 +/- 9.6 min vs. 13.8 +/- 5.2 min, P < 0.0001) in the 25 mg group than in the 12.5 mg group. In contrast, SpO2 was decreased in both groups; the magnitude of the decrease was greater in the 25 mg group than in the 12.5 mg group (4.0 +/- 0.8% vs. 1.6 +/- 1.0%, P < 0.0001). There were no differences in the time to reach the peak SctO2 or to reach the nadir SpO2 between the two groups. CONCLUSIONS: In patients given ICG for videoangiography, a 25 mg bolus results in a greater and more prolonged increase in SctO2 and a greater reduction in SpO2 than a 12.5 mg bolus, with no differences in the time to reach the peak SctO2 or to reach the nadir SpO2.
Anesthesia, General ; Arterial Pressure ; Endarterectomy, Carotid ; Heart Rate ; Humans ; Indocyanine Green* ; Oximetry* ; Oxygen ; Reading* ; Spectroscopy, Near-Infrared