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Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates a downstream effector, ROCK. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. There is growing evidence that ROCK inhibitors, such as fasudil and VX-210, can reduce injury in IS and SCI in animal models and clinical trials. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.

BACKGROUND Perioperative neurocognitive disorder (PND) is a postsurgical complication associated with neuroinflammation and impaired hippocampal neurogenesis, in which brain-derived neurotrophic factor (BDNF) plays a key role. Sarcopenia refers to age-related muscle loss that causes cognitive decline, muscle atrophy, and postoperative delirium. Rats with tail suspension (TS) were used to represent a low-activity model, which involves decreased hind limb function by TS. This hind limb unloading by TS can induce sarcopenia in 2 weeks. However, the relationship between PND and muscle atrophy is unclear. In this experiment, we investigated whether preoperative muscle atrophy induced by TS would affect neurogenesis and accelerate PND in rats. METHODS Sixty 21-week-old rats were assigned to 4 groups: the TS group, the TS with surgery (TS + S) group, the control group, and the control with surgery (control + S) group. After the abdominal manipulation under 3% sevoflurane anesthesia, cognitive function was assessed using the Morris water maze test and a fear-conditioning test. Neurogenesis was evaluated by checking BDNF secretion and immunohistochemical staining in the hippocampus. RESULTS The TS + S group showed impaired swimming latency (difference of means = 12.4 versus control + S; 95% confidence interval [CI], 2.0-22.7; P = .016) (difference of means = 15.2 versus TS; 95% CI, 0.4-30.1; P = .043) and path length (difference of means = 147.8 versus control + S; 95% CI, 20.7-274.9; P = .020) in the maze test and cued fear memory (difference of means = -26.0 versus TS; 95% CI, -46.4 to -5.6; P = .006) (difference of means = -22.3 versus control + S; 95% CI, -42.7 to -1.9; P = .026) in the fear-conditioning test. The postoperative levels of BDNF in the TS + S and TS groups were reduced compared with the other groups (P = .002). The number of neural precursors in the dentate gyrus was significantly lower in the TS + S group (P < .001). CONCLUSIONS We observed that preoperative hind limb muscle atrophy, indicated by TS, was associated with an increased occurrence of PND through the reduction in BDNF and neurogenesis after abdominal surgery in young adult rats. Therefore, we concluded that preoperative low skeletal muscle mass can induce PND due to impaired postoperative neurogenesis. Our findings might indicate that low-cost perioperative interventions, such as preoperative exercise, is beneficial to preventing PND.

Study objective To evaluate whether nasotracheal intubation using a fiberoptic bronchoscope reduces postoperative sore throat. Design Prospective, double-blinded, randomized, and controlled study. Setting Postoperative areas and surgical ward of a university hospital. Patients Seventy-four patients with American Society of Anesthesiologists physical status I-II who were scheduled for elective general anesthesia requiring nasotracheal intubation. Interventions Patients were randomized to one of two intubation groups, F (fiberoptic bronchoscope–guided) and M (Macintosh laryngoscope–guided), and after induction of general anesthesia, the patients' tracheas were intubated via the nose. Measurements The intensity of postoperative sore throat was evaluated using a numerical rating score (0=none, 10=severe) at 24 hours postoperatively, and the incidence of nasal mucosal trauma, time to completion of intubation, and hemodynamic responses were recorded and compared between groups. Main results The numerical rating score value was significantly lower in group F than in group M ( P =.0047), but the incidence of nasal mucosal trauma was comparable between the two groups. The median time to completion of intubation was shorter for group F than group M ( P Conclusions Fiberoptic bronchoscope–guided intubation is associated with less sore throat after nasotracheal intubation than M intubation. The time to completion of intubation was significantly shorter using the fiberoptic bronchoscope than that using the Macintosh laryngoscope.

Objective For patients with acute coronary syndrome (ACS), percutaneous coronary intervention (PCI) within 120 minutes from onset is recommended. A helicopter emergency medical service (HEMS) is useful for transporting ACS patients. The purposes of this study were to investigate whether patients with ACS in the eastern part of Hokkaido could be transported to a PCI hospital by HEMS and undergo PCI within 120 minutes and to clarify the factors most related to delayed access to PCI. Methods This was a retrospective cohort study that analyzed 513 patients diagnosed with ACS at our institution, an HEMS base/PCI hospital. We investigated transport modes for each patient and identified the processes by which access to PCI was delayed. Results HEMS reduced transport time compared with ground emergency medical services but did not contribute to access to PCI within 120 minutes. The most important factor was transport directly to a PCI hospital (P Conclusion HEMS did not achieve a total transport time of patients to a PCI hospital within 120 minutes from onset. Transport using HEMS is insufficient to access early PCI; patient condition must also be considered to determine whether to go through a non-PCI hospital.

To evaluate the current methods of surgical antimicrobial prophylaxis from the viewpoint of pharmacokinetics for patients undergo urologic surgery, this study was designed to measure the serum concentrations of two different prophylactic antimicrobial agents in different types of urologic surgery. This prospective study included 39 patients with prostate cancer, renal pelvic cancer, ureteral cancer or renal cancer treated by radical surgery from August 2005 to March 2006. Blood samples were taken intraoperatively at 30 min and 180 min after the beginning of the first administration. The half-life of the beta phase of cefazolin is 2.46 h and that of piperacillin is 0.7 h according to their manufacturers. The average serum concentration of cefazolin at 30 min was 144 μg/mL in the prostatectomy group and 175 μg/mL in the nephrectomy group. At 180 min, the average concentration of cefazolin was 37 μg/mL in prostatectomy group and 59 μg/mL in the nephrectomy group. The average concentration of piperacillin at 30 min was 134 μg/mL in the prostatectomy group and 137 μg/mL in the nephrectomy group. At 180 min, the average concentration of piperacillin was 10 μg/mL in the prostatectomy group and 22 μg/mL in the nephrectomy group. Thus, the concentration at 180 min after the beginning of infusion was different according to the half-life of each antimicrobial agent. Therefore, up-to-date guidelines for surgical antimicrobial prophylaxis that deal with additional types of intraoperative prophylaxis should be consulted if the operation exceeds two half-lives of the prophylactic antimicrobial agents used in real-life clinical practice.

Background Target-controlled infusions (TCIs) of propofol are commonly used for general anaesthesia. The Marsh model pharmacokinetic parameter set incorporated in TCI devices for propofol could increase bias when used in obese patients. Objective The purpose of this study was to assess the optimal predicted blood concentration (Cp) of 4.0 μg ml of propofol using a correction formula including BMI and to evaluate the influences on propofol concentration in obese patients. Design An open-label, comparative study. Setting Sapporo Medical University Hospital, Japan, from October 2011 to December 2013. Patients Seventy-five adults scheduled for elective surgery under general anaesthesia with the following exclusion criteria: less than 30 or more than 65 years of age; American Society of Anesthesiologists status 3 to 5; allergy to propofol; the daily use of psychoactive drugs; known or suspected drug or alcohol abuse; and cardiac, hepatic, renal or neurological impairment. Intervention Propofol was administered and maintained at a Cp of 4.0 μg ml using a TCI device programmed with the Marsh pharmacokinetic model. Arterial blood samples were collected at 15, 30, 60, 90, 120, 150 and 180 min after the start of the infusion, and the measured propofol concentration (Cm) was determined. After calculation of the adjustment formula using the corrected Cp of 69 patients, we then applied the corrected Cp to five other obese patients. Main outcome measures The median performance error (MDPE) and median absolute performance error (MDAPE) were calculated to measure bias at each time point. Results We analysed 333 samples from the 69 individuals. There was a significant correlation between BMI and Cm, which tended be greater than 4.0 μg ml in obese patients. Our new method improved MDPE and MDAPE from a range of 20 to 40 for both, to ranges of -11.3 to -1.8 and 8.8 to 11.5, respectively. Conclusion BMI influences blood propofol concentrations, leading to the possibility of overdosage of propofol in obese patients when the Marsh model is used to assess propofol concentration. Our new method using corrected Cp might improve this bias in obese, Japanese patients.

Severe pulmonary arterial hypertension is a significant risk factor for anesthetic management in patients undergoing even non-cardiac surgery. A 64-year-old female patient with severe pulmonary arterial hypertension was scheduled to undergo inguinal hernioplasty. Preoperative systolic pulmonary arterial pressure was 115 mmHg. We selected monitored anesthesia care with 0.2-0.5 μg x kg(-1) x hr(-1) dexmedetomidine and ultrasound-guided iliohypogastric block. Thereafter, LiDCOrapid was used to acquire the hemodynamic responses during surgery. Continuous iliohypogastric block produced postoperative pain relief and the supplemental analgesic was not needed. The monitored anesthesia care by dexmedetomidine and ultrasound guided continuous iliohypogastric block would be a safe procedure for patients with severe pulmonary arterial hypertension undergoing non-cardiac surgery. LiDCO rapid could be low invasive and useful as a hemodaynamic monitor in such a case.

We investigated the efficacy of ultrasound (US)-guided caudal epidural block for transrectal ultrasound (TRUS)-guided prostate biopsy.Sixty adult patients (ASA I or II) were enrolled in this study and randomized into two groups: group S receiving spinal block (n = 30) and group C receiving US-guided caudal epidural block (n = 30). We measured systolic blood pressure (SBP), heart rate (HR), and degrees of sensory and motor blockade. Procedural time for regional anesthesia was recorded.Six patients in group C were excluded from analysis because of insufficient block effect. Spinal block caused a significant decrease in SBP compared to that with US-guided caudal epidural block (P0.05). Degrees of sensory and motor blockade were significantly greater in group S than in group C (P0.05).US-guided caudal epidural block provided hemodynamic stability during TRUS-guided prostate biopsy. Furthermore, US-guided caudal epidural block effectively produced appropriate sensory blockade for TRUS-guided prostate biopsy with minimum motor blockade.

Summary Background and aim In reconstructive surgery for microtia during childhood, costal cartilage is used for pinna formation. Postoperative pain in the region from which the costal cartilage is taken is severe, which delays recovery after surgery. We evaluated prospectively whether continuous wound infiltration (CWI) of a local anesthetic (LA) reduces pain and enables rapid recovery compared with a single intercostal nerve block (ICNB). Method Forty-eight patients were randomly divided into two groups. In Group I, a single ICNB with 10 ml of 0.75% ropivacaine was performed at the end of surgery. In Group C, a catheter was inserted into the space between the abdominal external oblique muscle and the rectus abdominis muscle. Then, a 0.4-ml/kg bolus of 0.2% ropivacaine was administered, followed by continuous infusion at 2–4 ml/h for 48 h. Postoperative pain intensity evaluated using the Face Scale, dose of supplemental analgesics, and time until mobilization were evaluated. In Group C, the plasma concentrations of ropivacaine were analyzed. Results The pain intensity at rest was significantly lower in Group C than in Group I, but the values during coughing were comparable. The number of patients receiving a supplemental analgesic and the median number of doses were significantly larger in Group I than in Group C ( P = 0.029, P = 0.0007, respectively). The plasma concentrations of ropivacaine were within the safe range over 48 h. The times until mobilization were comparable. Conclusion CWI of 0.2% ropivacaine is a better and safe technique for postoperative pain management after costal cartilage graft harvest in children.

Objective: To assess the efficacy and adverse effects of fentanyl intravenous (IV) patient-controlled analgesia (PCA) compared with morphine IV-PCA in patients after major abdominal surgery. Methods: In a prospective, randomized, observer-blinded study, 40 patients with ASA physical status I-II who were scheduled to undergo major abdominal surgery. A standard general anesthetic was administered. Patients were randomly divided into two groups for 24h postoperatively: 1) Group F with fentanyl concentration of 25 μg/mL, background infusion of 25 μg/h, bolus of 25 μg, and lockout time of 10 min; and 2) Group M with morphine concentration of 1 μg/ml, no background infusion, bolus of 1 mg, and lockout time of 10 min. Numerical rating scale (NRS) pain scores at rest and on coughing and dose of additional PCA bolus and supplemental analgesic, and the incidence of adverse effects were assessed postoperatively during the first 24 h postoperatively. Results: Compared to Group M, Group F showed significantly lower postoperative pain scores at rest throughout the observation period and on coughing at 2 h after the end of surgery. Incidence of nausea and median dose of antiemetic drugs were comparable between groups. No respiratory complications were encountered in this study. Patient satisfaction scores were significantly higher in Group F than in Group M. Conclusions: Fentanyl IV-PCA provides more effective postoperative pain relief than morphine IV-PCA and greater patient satisfaction after abdominal surgery, without increasing the incidence of adverse effects.

As advances in cancer detection and treatment have increased the life expectancy of cancer patients, more attention to improving patient quality of life is needed. Among the various types of cancer pain, bone cancer pain is often debilitating, difficult to treat, and insufficiently relieved. Recently, a preclinical model of bone cancer pain has been developed [1]. This model has begun to provide insights into the mechanisms by which tumors cause pain and how cancer-pain-related sensory information is processed. Here we present new strategies for bone-cancer pain based on our data obtained from analyses of a mouse model. Murine model of bone-cancer pain

Background Bone cancer pain has a major impact on the quality of life of cancer patients but is difficult to treat. Therefore, development of a novel strategy for bone cancer pain is needed for improvement of the patient quality of life. In this study, we examined the analgesic effects of the combination of a transient receptor potential vanilloid subfamily 1 (TRPV1) antagonist and morphine on pain-related behaviours in a murine model of bone cancer pain. Methods C3H/HeJ mice underwent injection of osteolytic sarcoma cells into the intramedullary space of the femur. The analgesic effects of intraperitoneal morphine and the analgesic effect of a TRPV1 antagonist, SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], on bone cancer pain-related behaviours were examined. The analgesic effects of the combination of SB366791 and morphine on bone cancer pain were also examined. Results Intraperitoneal morphine significantly reduced the number of spontaneous flinches and improved ambulation only at the highest dose of 10 mg kg−1 whereas weight-bearing was not improved. Intraperitoneal SB366791 at doses of 0.3 and 1.0 mg kg−1, but not at a dose of 0.1 mg kg−1, reduced the number of spontaneous flinches, whereas neither weight-bearing nor ambulation was improved. Addition of a sub-analgesic dose of SB366791 (0.1 mg kg−1) to morphine significantly reduced the number of flinches and improved weight-bearing compared with the effects of morphine alone. Conclusions Our findings showed that the combination of morphine and SB366791 has potent analgesic effects on bone cancer pain. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.

ロピバカインはブピバカインに匹敵する長時間作用性の局所麻酔薬でありながら, 低濃度では選択的神経遮断作用に優れているという特徴をもつ. 婦人科および泌尿器科手術におけるロピバカインの主な用途は術中および術後の硬膜外への投与である. これらの手術では比較的下方レベルで硬膜外カテーテルを留置するため運動麻痺を生じさせにくいロピバカインは術後, 早期離床を促す意味で非常に有効である. しかしながら十分な鎮痛を得るためにはさらなる工夫が必要である.

Anti-coagulant management of cardiopulmonary bypass for the patient complicated with heparin-induced thrombocytopenia (HIT) is difficult. A woman of late 50's with a previous history of HIT was scheduled for mitral valve replacement, tricuspid valvuloplasty and coronary artery bypass graft. We knew that heparin antibody was negative by serologic and functional assay before the operation. According to the HIT guideline, we planned to use heparin only during cardiopulmonary bypass and to use argatroban for other catheters. Although the platelet count continued decreasing up to the 5th postoperative day unless the transfusion of platelets, heparin antibody was negative on the first postoperative day. But, it was thought that HIT would develop from 5 days to 10 days after using heparin. Therefore, we had to examine heparin antibody on the 5th postoperative day at least for the patients with a history of HIT. In the future, it is important to observe the patient carefully and examine heparin antibody.

The continuous subcutaneous infusion (CSI) technique is a simple, inexpensive method for managing postoperative pain. We examined the analgesic effects of CSI of buprenorphine in patients undergoing lumbar spinal fusion surgery.The patients were randomly assigned to one of three groups for postoperative pain management: control group (n = 17), high-dose buprenorphine group (BH group, n = 17), and low-dose buprenorphine group (BL group, n = 16). Infusion solutions containing buprenorphine at concentrations of 25.0 and 16.7 microg x ml(-1) combined with droperidol at a concentration of 52.0 microg x ml(-1) were used in the BH and BL groups, respectively; and an infusion solution containing droperidol at a concentration 52.0 microg x ml(-1) was used in the control group. CSI of each solution was started at a rate of 1 ml x h(-1) and was continued for 48 h.The BH and BL groups showed significantly lower scores than the control group on the Visual Analogue Scale. There were significantly fewer administrations of flurbiprofen as a supplemental analgesic in the BL and BH groups than in the control group. The incidences of sedation and nausea were comparable in the three groups. The median number of administrations of flurbiprofen was significantly less in the BH group than in the control group on the day of the operation and on the first postoperative day, whereas the number in the BL group was less than that in the C group only on the day of the operation.CSI of buprenorphine effectively reduces pain after lumbar spinal fusion surgery without apparent side effects. This technique is simple and useful for postoperative pain management.

31-year-old female with hypersensitivity to local anesthetics and neuromuscular blocking agents presented for emergency Cesarean section. We successfully performed I-gel-assisted tracheal intubation without using neuromuscular blockers. We believe this method would be helpful in selected situations.

Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia, and emotional abnormalities such as anxiety and depression. Although spinal cord microglia are involved in abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain-induced anxiety. Here, we examined the involvement of bone marrow (BM)-derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. We prepared partial sciatic nerve ligations (PSNL) in mice that received bone marrow transplantation from green fluorescent protein (GFP)-Tg mice after irradiation with head protection, and examined GFP-positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)-1β and C-C chemokine receptor type 2 (CCR2). In addition, neurons in the CeA highly expressed monocyte chemotactic protein-1 (MCP-1), a ligand for CCR2, in PSNL-treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis is involved in the recruitment of BM-derived microglia. Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1β receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron-microglia interactions might be important in the pathogenesis of neuropathic pain-induced anxiety.

In cases of facial burns caused by molten asphalt, examination for possible airway burns and early removal of the asphalt should be carried out to prevent chemical-induced tissue damage and infection. However, asphalt that has adhered to tissues is difficult to remove. A 35-year-old male with burns caused by molten asphalt was scheduled for emergency debridement. He had 6% body surface area burns on his face and neck. He was not able to open his eyes due to the adherence of asphalt. His respiratory condition was stable and a perioperative fiberoptic view revealed no airway burns. After awake intubation, orange peel oil was used to remove the asphalt from his face and eyes. Since orange peel oil does not contain any harmful substances, it is effective for removing asphalt without causing tissue damage.

The purpose of this study was to investigate the incidence of cannot intubate-cannot ventilate (CICV) during general anesthesia during a 3-year period in a network of university hospitals and to evaluate the events related to it.A retrospective multicenter questionnaire survey of CICV, based on medical record review, was conducted over a 3-year period (January 2010-December 2012) in Hokkaido, Japan. All cases were assessed in terms of the suspected risk factors of CICV, the clinical course during anesthesia, and the prognosis.Responses were obtained from 20 of 21 institutions (95%) surveyed. The incidence of CICV was 3 of 97,854 cases conducted under general anesthesia (0.003%). All incidents occurred during induction of general anesthesia. In two of the three cases, difficult airway was predicted preoperatively. In all these three cases, mask ventilation became impossible after repeated intubation attempts with devices such as the Macintosh laryngoscope, the Airwayscope, or a fiberoptic bronchoscope. A laryngeal mask was inserted in one case, but the lungs could not be adequately ventilated. Emergency tracheotomy was eventually performed in all the CICV cases. Although two of the patients did not have postoperative neurological sequelae, severe and permanent brain damage occurred in one patient.In our survey, we found that the incidence of CICV during a 3-year period (2010-2012) was 0.003% or 1 in 32,000 cases. The three CICV situations occurred after repeated intubation attempts with multiple devices. The appropriate airway devices to be used in a particular difficult airway situation should be carefully considered before performing multiple attempts.

A 5-year-old girl with metatropic dysplasia was scheduled for an operation of posterior cervical fusion. This disease is a rare skeletal dysplasia characterized by long trunk and short limbs and severe scoliosis. As she had been suspected to have a difficult airway, we attempted fiberoptic intubation with a nasopharyngeal airway to prevent airway obstruction. The nasopharyngeal airway ensured a patent airway sufficient oxygenation, and anesthesia. Thus, it was possible to perform a fiberoptic intubation via the opposite nostril with no adverse event. The combination of a nasopharyngeal airway and fiberoptic guided tracheal intubation is a reliable and safe procedure for small children with metatropic dysplasia and difficult airway.

Spinal progressive muscular atrophy (SPMA) is a rare lower motor neuron disease in which anesthetic management is often difficult as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents. A 43-year-old female patient with SPMA was scheduled to undergo laparotomy for ovarian teratoma. Her vital capacity was only 530 ml and % volume capacity was 22.2%, indicating a severe restrictive pulmonary disfunction. We selected general and epidural anesthesia for the surgery. Anesthesia was induced by propofol and the trachea was intubated with additional topical anesthesia. Spontaneous ventilation was kept during anesthesia without neuromuscular blocking agents, and systemic and epidural opioids were avoided to evade their respiratory depression. Because of severe spine scoliosis syndrome, we inserted an epidural catheter into the epidural space under radiographic monitoring for safety and precision. Postoperative pain control was stable using continuous epidural infusion of 0.2% ropivacaine without neurological adverse effects. One day after surgery, the trachea was extubated and respiratory function did not aggravate. Despite the controversy surrounding the use of neuraxial blocks in motor neuron diseases, in this case, epidural anesthesia was useful to keep the respiratory function stable.

Optimal dose of local anesthetics for supraclavicular brachial plexus block (BPB) is still unknown. We prospectively investigated the analgesic effect of ultrasound-guided continuous supraclavicular BPB with ropivacaine at different infusion rates.Thirty-nine patients scheduled to undergo shoulder surgery were randomly assigned to four groups; receiving no continuous BPB (control group, n = 10), BPB with 0.2% of ropivacaine at an infusion rate of 4 ml x hr(-1) (n = 12), BPB with 6 ml x hr(-1) (n = 12) or BPB with 8 ml x hr(-1) (n = 5). All patients were permitted to receive nonsteroidal anti-inflammatory drugs (NSAIDs) after surgery. Visual analogue scale (VAS) for postoperative pain was assessed and frequencies of the requirement of NSAIDs were recorded in each group.The pain scores during 24 hours after surgery in the 6 ml x hr(-1) group (3-24 mm) were significantly lower than those in the 4 ml x hr(-1) group (4-42 mm) and control group (6-56 mm). Mean frequency of administrations of NSAIDs for 24 hours after surgery in the 6 ml x hr(-1) (0.8 +/- 0.8) group was significantly lower than that in the control group (1.7 +/- 1.0). Continuous administration in two cases in the 8 ml x hr(-1) group was discontinued due to leakage of local anesthetics and headache.Continuous supraclavicular BPB with 0.2% ropivacaine at 6 ml x hr(-1) is effective for the pain management after shoulder surgery and is not an excess dose.

IMPLICATIONS: We experienced a case of unanticipated difficult intubation with direct laryngoscopy because of narrowing of the retropharyngeal air space and laryngeal vestibulum. It is suggested that three-dimensional computed tomography is useful for evaluating both the abnormality of an airway and its relationship to surrounding tissue.

Background Bone cancer pain has a strong impact on the quality of life of patients, but it is difficult to treat. Therefore, development of a novel strategy for the treatment of bone cancer pain is needed for improvement of patient quality of life. This study examined whether selective spinal cannabinoid receptor 1 (CB1) activation alleviates bone cancer pain and also examined the spinal expression of CB1. Methods A bone cancer pain model was made by implantation of sarcoma cells into the intramedullary space of the mouse femur. In behavioral experiments, the authors examined the effects of activation of spinal CB1 and inhibition of metabolism of endocannabinoid on bone cancer-related pain behaviors. Immunohistochemical experiments examined the distribution and localization of CB1 in the superficial dorsal horn of the spinal cord using specific antibodies. Results Spinal CB1 activation by exogenous administration of a CB1 agonist arachidonyl-2-chloroethylamide reduced bone cancer-related pain behaviors, including behaviors related to spontaneous pain and movement-evoked pain. In immunohistochemical experiments, although mu-opioid receptor 1 expression was reduced in the superficial dorsal horn ipsilateral to the site of implantation of sarcoma cells, CB1 expression was preserved. In addition, CB1 was mainly expressed in the axon terminals, but not in the dendritic process in the superficial dorsal horn. Conclusion Spinal CB1 activation reduced bone cancer-related pain behavior. Presynaptic inhibition may contribute to the analgesic effects of spinal CB1 activation. These findings may lead to novel strategies for the treatment of bone cancer pain.

Although local administration of endothelin-1 (ET-1) is known to evoke spontaneous pain, the mechanism of ET-1-induced pain has not been elucidated. We investigated the involvement of protein kinase C (PKC) and transient receptor potential vanilloid subfamily 1 (TRPV1) in ET-1-induced pain-like behavior. Intraplantar ET-1 evoked pain-like behaviors, including licking, flinching, and biting, in a dose-dependent manner in wild-type mice. ET-1 -induced pain-like behavior was attenuated by an endothelin type A receptor antagonist but not by PKC inhibitors and was also attenuated in TRPV1-deficient (KO) mice. In addition, we found a significant reduction of spinal Fos expression caused by the same dose of ET-1 in KO mice compared with that in wild-type mice. This study showed that endothelin type A receptor and TRPV1 are involved in ET-1-induced pain-like behaviors but failed to reveal the contribution of PKC.

Endothelin-1 (ET-1) plays an important role in peripheral pain processing. However, the mechanisms of the nociceptive action of ET-1 have not been fully elucidated. In this study, we investigated the contribution of transient receptor potential vanilloid subfamily 1 (TRPV1) to ET-1-induced thermal hyperalgesia. Intraplantar ET-1-induced thermal hyperalgesia was examined by assessing the paw withdrawal latency to noxious heat stimuli. In electrophysiological study, whole-cell patch-clamp recordings were performed to investigate the interaction of ET-1 and TRPV1 using human embryonic kidney 293 (HEK293) cells expressing endothelin type A receptor (ET(A)) and TRPV1. Intraplantar ET-1 (3, 10 and 30 pmol) produced thermal hyperalgesia in a dose-dependent manner. Thermal hyperalgesia was attenuated by the inhibition of ET(A) and protein kinase C (PKC) but not that of ET(B). ET-1-induced thermal hyperalgesia was significantly attenuated in TRPV1-deficient mice compared with that in wild-type mice. In voltage-clamp experiments, 10 nM capsaicin evoked small inward currents in HEK293 cells expressing TRPV1 and ET(A). In the presence of ET-1, capsaicin produced much larger current responses (P

Although micro opioid receptor (MOR) agonists are used for treatment of most types of pain, a recent study has suggested that the sensitivity of bone cancer pain to systemic morphine was lower than that of inflammatory pain. However, the reasons for this have remained unclear. In this study, MOR expression and the analgesic effects of morphine in a bone cancer model were compared with those in an inflammatory pain model. A bone cancer pain model and an inflammatory pain model were made by implantation of sarcoma cells into the intramedullary space of the femur and hind-paw injection of complete Freund's adjuvant (CFA), respectively. In a behavioral study, sarcoma-implanted mice showed flinching behavior of magnitude comparable to that induced by CFA injection. The flinching behavior of sarcoma-implanted mice was less sensitive to intrathecal morphine than that of CFA-injected mice. Western blot analysis showed that MOR expression in the dorsal root ganglion (DRG) ipsilateral to sarcoma implantation was significantly reduced, while that in the DRG ipsilateral to CFA injection was increased. In sarcoma-implanted mice, the percentage of MOR-positive DRG neuronal profiles was lower than that in control mice (30.3% vs. 45.2%). In particular, MOR expression was reduced among calcitonin gene-related peptide- and transient receptor potential vanilloid subfamily 1-positive DRG neuronal profiles, which are considered to be involved in the generation of bone cancer pain (from 61.5% to 41.5% and from 72.1% to 48.4%, respectively). These results suggest that down-regulation of MOR in the distinct populations of DRG neurons contributes to the fact that higher doses of morphine are needed to produce analgesia in bone cancer as compared with those used in non-malignant inflammatory situations.

Bone cancer pain has a strong impact on the quality of life of patients but is difficult to treat. Therefore, the mechanisms of bone cancer pain require elucidation for the purpose of development of new therapeutics. A recent study showed that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) was involved in bone cancer pain. In this study, we re-evaluated the analgesic effects of pharmacological blockade of TRPV1 using the potent TRPV1 antagonist 5-iodoresiniferatoxin (I-RTX) and examined whether bone cancer can change TRPV1 expression and distribution in the primary sensory neurons in a mouse model of bone cancer pain. Implantation of osteosarcoma into the femur induced ongoing and movement-evoked bone cancer-related pain behaviors. These behaviors were significantly reduced by i.p. administration of I-RTX, compared with vehicle. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that TRPV1 level was significantly increased in dorsal root ganglions (DRGs) ipsilateral to sarcoma implantation. Immunohistochemical analysis showed that implantation of osteosarcoma induced not only an increase in the percentage of TRPV1-positive neurons among DRG neurons (24.3+/-1.3% in sham mice and 31.2+/-1.3% in mice with osteosarcoma implantation, P

Several studies have suggested that acid-sensing ion channel 2 (ASIC2) plays a role in mechanoperception and acid sensing in the peripheral nervous system. We examined the expression and distribution of ASIC2 in the rat dorsal root ganglion, the co-localization of ASIC2 with tropomyosin-related kinase (trk) receptors, and the effects of axotomy on ASIC2 expression. ASIC2 immunoreactivity was observed in both neurons and satellite cells. ASIC2-positive neurons accounted for 16.5 +/- 2.4% of the total neurons in normal dorsal root ganglion. Most ASIC2-positive neurons were medium-to-large neurons and were labeled with neurofilament 200 kD (NF200). Within these neurons, ASIC2 was not evenly distributed throughout the cytoplasm, but rather was accumulated prominently in the cytoplasm adjacent to the axon hillock and axonal process. We next examined the co-localization of ASIC2 with trk receptors. trkA was expressed in few ASIC2-positive neurons, and trkB and trkC were observed in 85.2% and 53.4% of ASIC2-positive neurons, respectively, while only 6.9% of ASIC2-positive neurons were co-localized with trkC alone. Peripheral axotomy markedly reduced ASIC2 expression in the axotomized dorsal root ganglion neurons. On the other hand, intense ASIC2 staining was observed in satellite cells. These results show that ASIC2 is expressed in the distinct neurochemical population of sensory neurons as well as satellite cells, and that peripheral axotomy induced marked reductions in ASIC2 in neurons.

To assess the analgesic and side effects of the continuous epidural infusion of 0.2% ropivacaine combined with morphine compared to both drugs alone.In this study, both observers and patients were blinded to patient group assignment. Sixty patients scheduled to undergo lower abdominal surgery were enrolled. Patients were randomized to one of three postoperative treatment groups: 1) combination group (a combination of 0.2% ropivacaine and 0.003% morphine); 2) morphine group (0.003% morphine); or 3) ropivacaine group (0.2% ropivacaine). Postoperatively, all solutions were administered epidurally at a rate of 6 mL.hr(-1) for 24 hr. Patients were given iv flurbiprofen as a supplemental analgesic on demand.The combination group showed lower visual analogue scale scores than those of patients receiving either drug alone, both at rest and on coughing. The combination group showed a slight motor block at two hours after the continuous epidural infusion, while the ropivacaine and morphine groups did not show any motor block. The incidence of itching was significantly increased in the morphine and combination groups, compared to the ropivacaine group. There was no significant difference between the numbers of patients with nausea in the three groups. No hypotension or respiratory complications were observed in the three groups.The combination of epidural 0.2% ropivacaine and 0.003% morphine has more effective analgesic effects than either of the drugs alone for postoperative pain relief after lower abdominal surgery.

A 50-year-old woman was scheduled for laparoscopic cholecystectomy under general anesthesia. She was suffering from Charcot-Marie-Tooth (CMT) disease for 21 years, and implanted with a permanent pacemaker for IIIrd degree AV block. Anesthesia was induced with fentanyl and propofol, and maintained with oxygen-air-sevoflurane. Neuromuscular blockade was not used because of the presence of peripheral neuropathy and respiratory muscle weakness. We suggest that sevoflurane anesthesia might be useful for anesthetic management of CMT patient with a risk of postoperative respiratory failure.

Beta blockers are thought to exert beneficial effects on the ischemic heart. The authors examined the effects of landiolol (ONO 1101), a highly selective beta1 antagonist, propranolol, a nonspecific beta blocker, and esmolol, a selective beta1 antagonist, on postischemic contractile recovery. Drugs were given prophylactically.Ischemia-reperfusion in isolated guinea pig hearts was induced by stopping the perfusion for 45 min and reperfusing for 60 min. Hearts (n = 7 in each group) were treated with or without propranolol (1 or 10 microM), esmolol (5 or 50 microM), or landiolol (20, 100 or 500 microM) ten minutes before inducing ischemia.At the end of reperfusion, left ventricular pressure (LVP) recovered to 64 +/- 3% of the baseline value in the control group. With 1 and 10 microM propranolol, LVP recovered to 90 +/- 5% and 100 +/- 6% of the baseline value at 60 min after reperfusion, respectively. Fifty microM but not 5 microM of esmolol resulted in restoration of LVP to 97 +/- 17% of the pre-ischemic value at 60 min after reperfusion. In hearts pretreated with 100 and 500 microM landiolol, LVP was restored to 109 +/- 5% and 104 +/- 5% of the baseline value, respectively. Landiolol 100 microM did not depress LVP in the pre-ischemic period.The present study shows that landiolol, an ultra-short-acting cardioselective beta1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three beta blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period.