Masaru Tobe

Monoamine-Dependent, Opioid-Independent Antihypersensitivity Effects of Intrathecally Administered Milnacipran, a Serotonin Noradrenaline Reuptake Inhibitor, in a Postoperative Pain Model in Rats

The neurotransmitters serotonin (5-HT) and noradrenaline (NA) have important roles in suppressing nociceptive transmission in the spinal cord. In the present study, we determined the efficacy and nature of the antihypersensitivity effects of milnacipran, a 5-HT and NA reuptake inhibitor (SNRI), in the spinal cord in a rat model of postoperative pain. Sprague-Dawley rats were used in all experiments. An incision was made on the plantar aspect of the hind paw. Mechanical hypersensitivity was measured by determining the withdrawal threshold to von Frey filaments applied to the paw. Drugs were administered intrathecally 24 h after paw incision. Microdialysis studies of the dorsal horn of the lumbar spinal cord were also performed to measure 5-HT and NA levels after systemic injection of milnacipran. Milnacipran (1–30 μg) produced dose-dependent antihypersensitivity effects. The effect lasted 6 h after the 30-μg injection. Doses of 30 μg or less produced no abnormal behavior. The peak antihypersensitivity effect of 10 μg of milnacipran was blocked by intrathecal pretreatment with antagonists of the α2-adrenoceptor (idazoxan; 30 μg) or 5-HT receptors (methysergide; 30 μg). Intrathecal pretreatment with 30 μg of naloxone, a μ-opioid receptor antagonist, did not reverse the effect of milnacipran. Isobolographic analysis indicated antinociceptive synergism between milnacipran and morphine. Microdialysis studies revealed that milnacipran increased both 5-HT and NA levels in the spinal dorsal horn. These findings suggest that the antihypersensitivity effect of intrathecal milnacipran in the postoperative pain model is monoamine-mediated. Combined administration of an SNRI with morphine might be a promising treatment to suppress postoperative hypersensitivity.

Percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy

IntroductionAlthough Gasserian ganglion block is an established treatment for trigeminal neuralgia, the foramen ovale cannot always be clearly visualized by classical X-ray radiography. We present a new method for percutaneous radio-frequency thermocoagulation of the Gasserian ganglion, in which computed tomography (CT) fluoroscopy is used to guide needle placement.MethodsIn the present study, 15 patients with trigeminal neuralgia underwent percutaneous radio-frequency thermocoagulation of the Gasserian ganglion guided by high-speed real-time CT fluoroscopy.ResultsTrigeminal neuralgia was improved in all patients after treatment without any severe complications. Moderate dysesthesia occurred in only one case.ConclusionCT fluoroscopy-guided percutaneous radio-frequency thermocoagulation of the Gasserian ganglion was safe, quick, and effective for patients with intractable idiopathic trigeminal neuralgia.

Long-term Effect of Sciatic Nerve Block with Slow-release Lidocaine in a Rat Model of Postoperative Pain

Background:Postoperative pain management is important for preventing perioperative complications. The authors examined the effectiveness of controlled-release lidocaine for sciatic nerve block in a rat model of postoperative pain. Methods:The authors created a novel slow-release lidocaine sheet (SRLS) with polylactic-coglycolic acid. In male Sprague-Dawley rats (postoperative pain model), the authors applied the SRLS, lidocaine alone, or polylactic-coglycolic acid (control) near the ipsilateral sciatic nerve just before making the paw incision. Mechanical hypersensitivity was assessed using von Frey filaments, and c-fos expression was examined in the spinal cord dorsal horn at segments L4–L5. Neurotoxicity and muscle toxicity were also evaluated via histopathology. Results:The SRLS (30%, w/w) continuously released lidocaine for 1 week in vitro. The withdrawal threshold in the SRLS-treated group was higher than that in the control group at all time points measured (2 h to 7 days). The withdrawal threshold in the lidocaine-treated group was higher than that in the control group only at 2 h after paw incision. The mean number of c-fos immunoreactive neurons in the SRLS-treated group was lower than in the control group at 2, 5, and 48 h after paw incision and lower than in the lidocaine-treated group at 5 and 48 h after paw incision. On histopathology, signs of inflammation were only slightly present in the muscle and nerve tissues of the SRLS-treated group. Conclusions:Single treatment with the SRLS inhibited hyperalgesia and c-fos expression in the spinal cord dorsal horn for 1 week. Slow-release local anesthetics are promising for the management of postoperative pain.

Effects of cardiopulmonary resuscitation at high altitudes on the physical condition of untrained and unacclimatized rescuers.

OBJECTIVE The authors experienced a case of prolonged cardiopulmonary resuscitation (CPR) on Mount Fuji (3776 m) that demanded strenuous work by the rescuers. The objective of this study was to provide information regarding the physiologic effects on the rescuers of performing CPR at moderate altitude. METHODS The effects of CPR at 2700 m and 3700 m above sea level on the physical condition of the rescuers were studied in 8 male volunteers. RESULTS Cardiopulmonary resuscitation for 5 minutes at 3700 m significantly reduced arterial blood oxygen saturation and increased rate-pressure products (P < .05). Scores on the Borg scale, a subjective score of fatigue, after CPR action at 2700 m (P < .05) and 3700 m (P < .01) were higher than the scores at sea level. CONCLUSIONS Prolonged CPR at high altitude exerts a significant physical effect upon the condition of rescuers. A role for mechanical devices should be considered wherever possible.

Percutaneous Radiofrequency Mandibular Nerve Rhizotomy Guided by High-Speed Real-Time Computed Tomography Fluoroscopy

We present a new method of percutaneous radiofrequency mandibular nerve rhizotomy for pain relief in the mandibular region, in which needle placement is guided by high-speed real-time computed tomography (CT) fluoroscopy. Eleven patients (13 procedures) with idiopathic trigeminal neuralgia underwent the procedure. CT fluoroscopy simultaneously provided 3 slices (1-mm interval series, craniocaudally) in 1 fluoroscopic view, allowing for accurate needle placement. Trigeminal neuralgia improved in all patients without severe complications. The mean numerical rating scales of pain intensity (±SD) decreased from 6.5 (±1.8, pretreatment) to 1.8 (±1.7, 1 month after treatment) and to 0.9 (±1.0, 3 months after treatment). Our limited-case series suggests potential advantages for the new CT fluoroscopy guidance, but these findings await confirmation from randomized controlled trials and large-case series.

Anatomic analysis of computed tomography images obtained during fluoroscopic computed tomography-guided percutaneous lumbar sympathectomy

PurposeThe fluoroscopic computed tomography (CT)-guidance technique increases the accuracy and safety of needle placement for percutaneous lumbar sympathectomy. The aim of the present study was to provide anatomic data from CT images and to discuss the safest route for needle insertion.MethodsWe retrospectively analyzed CT images that were obtained from 25 patients (14 men, 11 women; 37—89 years of age [mean, 68.4 years]) during fluoroscopic CT-guided percutaneous lumbar sympathectomy. The anatomy around the inserted needle was measured and the correlations between patient characteristics and the procedure-related distances were assessed.ResultsThe distance from the midline (spinous process) to the entry point and the depth to the target site correlated with body size, especially height and weight. The maximal distance from midline to the insertion point in the range of safe needle insertion at L2 was less than 7.0 cm in approximately 20% of the patients.ConclusionThe present study was performed to determine the anatomic details required to guide safe percutaneous lumbar sympathectomy based on CT images. The use of CT guidance is recommended for lumbar sympathectomy, especially at the L2 spinal level.

Long-term effect of epidural injection with sustained-release lidocaine particles in a rat model of postoperative pain

BACKGROUND Single applications of sustained-release local anaesthetics may provide prolonged pain relief without requiring indwelling catheters, but have not yet been investigated for epidural postoperative pain management. We synthesized injectable sustained-release lidocaine particles (SRLPs) from biodegradable polymers and examined their effect in a rat model of postoperative pain. METHODS Two types of polylactic acid particles, SRLP-10 and SRLP-25, containing 10% or 25% lidocaine, respectively, were generated and the lidocaine release was evaluated in vitro for 14 days. The SRLPs were then injected epidurally in the male Sprague-Dawley rats immediately before they received a hindpaw incision (the postoperative pain model), and hindpaw hypersensitivity was evaluated with the von Frey test. Motor paralysis and coordination were also assessed using a paralysis score and rota-rod test. Neurotoxicity and inflammation of the spinal cord, cauda equina, and tissue surrounding the injection site were histologically evaluated. RESULTS In vitro, SRLP-10 and SRLP-25 released lidocaine over 7 and 3 days, respectively. The in vivo injection of SRLP-10 (80 mg) produced anti-hypersensitivity with no evidence of motor paralysis for 7 days after the paw incision, and SRLP-25 (60 mg) inhibited postoperative hypersensitivity for 7 days. Temporary motor paralysis (15 min) was observed after the injection of SRLP-25 (even with 40 mg). Foreign body reactions were observed around the SRLP injection site at 1 and 4 weeks after injection. No histopathological changes were observed at 1 or 4 weeks. CONCLUSIONS The epidural injection of SRLPs produced prolonged anti-hypersensitivity in a rat model of postoperative pain with no major complications.

Local anesthetic toxicity: acute and chronic management

Local anesthetics are commonly used medicines in clinical settings. They are used for pain management during minor interventional treatments, and for postoperative care after major surgeries. Cocaine is the well‐known origin of local anesthetics, and the drug and related derivatives have long history of clinical usage for more than several centuries. Although illegal use of cocaine and its abuse are social problem in some countries, other local anesthetics are safely and effectively used in clinics and hospitals all over the world. However, still this drug category has several side‐effects and possibilities of rare but serious complications. Acute neurotoxicity and cardiac toxicity are derived from unexpected high serum concentration. Allergic reactions are observed in some cases, especially following the use of ester structure drugs. Chronic toxicity is provoked when nerve fibers are exposed to local anesthetics at a high concentration for a long duration. Adequate treatments for acute toxic reactions can secure complete recovery of patients, and careful use of drugs prevents long‐lasting neurological complications. In addition to respiratory and circulatory management, effectiveness of lipid rescue in the acute toxicity treatment has been certified in many clinical guidelines. Prevention of the use of high concentration of local anesthetics is also validated to be effective to decrease the possibility of nerve fiber damage.

Effect of different blood glucose target levels on the incidence of hypoglycemia during insulin therapy in the intensive care unit (在重症监护病房中使用胰岛素治疗后不同的血糖目标水平对低血糖发生率的影响)

Prior to 2003, the target blood glucose level at our institute was <200 mg/dL. This target was reassessed in 2004 and again in 2006 based on reports showing decreased mortality in patients with target glucose levels between 80 and 110 mg/dL and results from subsequent randomized controlled trials. The aim of the present study was to determine the incidence of hypoglycemia due to IIT. The primary endpoint of the study was the incidence of hypoglycemia, with secondary outcomes of morbidity and mortality in three different periods.

Hemodynamic changes during electroconvulsive therapy under propofol anesthesia

Informed consent was obtained from each patient or, where necessary, the appropriate relative. The study protocol was approved by a local Clinical Study Committee, which considers the ethics and legal aspects of clinical investigations. ECT was prescribed to 30 patients suffering from endogenous depression. The patients ranged from 15 to 78 years of age and were in good physical heath. No patient had any known cardiovascular or cerebrovascular complication or drug allergy. All patients were treated more than six times (three times per week at 2-day intervals). The data were obtained in the second ECT trial in each case. To avoid an unfavorable parasympathetic reflex, atropine (0.01mg·kg 1) was given intramuscularly as premedication. Arterial blood pressure was measured continuously at the right radial artery by a tonometric BP monitor (CBM-7000; Colin, Komaki, Japan). General anesthesia was induced with propofol (1mg·kg 1). Propofol was administered over 15 s through an intravenous catheter. After loss of consciousness, succinylcholine chloride (1mg·kg 1) was administered and ventilation was assisted by a face mask with 100% oxygen. One minute after succinylcholine chloride injection, an electrical current was applied bilaterally for 5s at the minimal stimulus intensity, which had been determined in the first ECT trial by stepwise increasing electrical intensity. The electroshock stimulus was delivered by a trained psychiatrist using an ECT-stimulator (CS-1; Sakai Iryo, Tokyo, Japan). The efficacy of electrical stimulation was determined by the so-called tourniquet technique, which requires observation of convulsive movements of the distal leg, around which an inflated tourniquet was set to block the distribution of muscle relaxant. The end-expiratory CO2 partial pressure (endtidal CO2) at the nostrils and arterial blood oxygen saturation (SpO2) were monitored by a respiration monitor (Capnomac Ultima; Datex, Helsinki, Finland). The