Osamu Satoh

Roles of monoaminergic, glycinergic and GABAergic inhibitory systems in the spinal cord in rats with peripheral mononeuropathy

The current study was designed to determine if the monoaminergic descending inhibitory system and the glycinergic and GABAergic inhibitory systems were activated in the spinal cord in the presence of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve. The time course of withdrawal latencies to thermal stimuli were assayed in lesioned and sham-operated rats. The levels of monoamines (serotonin; 5-HT, noradrenaline, and dopamine), glycine and gamma-aminobutyric acid (GABA) in the dorsal half of the spinal cord were measured using HPLC with electrochemical detection. Furthermore, on day 7 after nerve ligation, intrathecal methysergide, yohimbine, strychnine or bicuculline was administered in order to investigate the roles of these inhibitory neuromodulators in this pathological pain state. The levels of 5-HT and noradrenaline significantly increased in both ipsi- and contralateral sides of the dorsal half of the lumbar spinal cord in the lesioned, but not sham-operated animals. The levels of glycine and GABA in the ipsilateral dorsal half of the spinal cord increased significantly and were significantly higher than in the contralateral side. Intrathecal antagonists of 5-HT, noradrenaline, glycine and GABA produced enhancement of the magnitude of hyperalgesia on the lesioned hindpaw. We also examined the effects of four daily single treatments with intrathecal MK-801 beginning 15 min prior to nerve ligation on the development of thermal hyperalgesia and on the contents of the neuromodulators in the ligation model. MK-801 treatment effectively abolished the increases in 5-HT, noradrenaline, glycine and GABA levels as well as preventing the development of hyperalgesia. The results of the present study suggest that the pathological pain state activates or increases the activity of these inhibitory systems.

Spinal antinociceptive action of an N-type voltage-dependent calcium channel blocker and the synergistic interaction with morphine

Background Four different voltage‐dependent calcium channels (L‐, N‐, T‐, and P‐types) are distinguished in the central nervous system. Both L‐ and N‐type calcium channels have been implicated in the release of neurotransmitters from sensory neurons in the spinal cord. It has been demonstrated that intrathecal L‐type calcium channel blockers, which alone do not exhibit any antinociceptive effects, potentiate the antinociceptive effects of intrathecal morphine. The current study was designed to investigate the antinociceptive effects of the intrathecally administered N‐type calcium channel blocker, omega‐conotoxin GVIA (omega‐CgTx). The interaction between morphine and omega‐CgTx at the level of the spinal cord also was examined. Methods In male Sprague‐Dawley rats, lumbar intrathecal catheters were chronically implanted. Tail flick and mechanical paw pressure tests were used to assess thermal and mechanical nociceptive thresholds, respectively. Morphine, omega‐CgTx, or a combination of morphine and omega‐CgTx was administered intrathecally, and the nociceptive thresholds were determined. Isobolographic analyses were used to define the nature of the functional interactions between morphine and omega‐CgTx. Results Intrathecal omega‐CgTx produced antinociception in a dose‐ and time‐dependent manner. Isobolographic analyses revealed that intrathecal omega‐CgTx and morphine interacted synergistically in both nociceptive tests. Conclusions This study indicates the importance of the N‐type calcium channel in the spinal cord on nociception and suggests the functional interaction between the N‐type calcium channel blocker and opioid at the level of the spinal cord.

Analgesic effect of epidural neostigmine after abdominal hysterectomy.

STUDY OBJECTIVE To evaluate the effects of epidurally administered neostigmine on pain after abdominal hysterectomy. DESIGN Prospective, randomized, double-blind study. SETTING Teaching hospital. PATIENTS 45 ASA physical status I adult patients scheduled for abdominal hysterectomy. INTERVENTIONS All patients received identical general and epidural anesthesia. At the end of the surgery, they received epidural bupivacaine (10 mg) with either saline (control group, n = 15), 5 micro g/kg (5-micro g group, n = 15), or 10 micro g/kg neostigmine (10-micro g group, n = 15). Postoperatively, 50 mg diclofenac suppository was given for pain relief on patient demand. MEASUREMENTS AND MAIN RESULTS The time to first diclofenac administration and the number of times diclofenac was required during the first 24 postoperative hours were recorded. Pain was assessed using a 10-cm visual analog pain scale (VAS) at rest at the first diclofenac request, and at 15 and 24 hours after surgery. The time to first diclofenac administration was significantly longer (p < 0.05) in the 10-micro g group (223 +/- 15 min) than in the control (78 +/- 17 min) or 5-micro g groups (88 +/- 18 min). However, epidural neostigmine at both doses did not reduce the number of postoperative diclofenac administrations. There were no differences in VAS among the three groups. CONCLUSIONS Epidural neostigmine of 10 micro g/kg in bupivacaine provides a longer duration of analgesia than does bupivacaine alone or with 5 micro g/kg of neostigmine after abdominal hysterectomy.

Suppression of the thyrotropin response to thyrotropin-releasing hormone and its association with severity of critical illness.

Objective: To study whether the suppression of the thyrotropin (thyroid‐stimulating hormone, TSH) response to thyrotropin‐releasing hormone (TRH) correlates with severity of illness and death in patients with nonthyroidal critical illness. Design: Prospective study. Setting: Intensive care unit (ICU) of a university hospital. Patients: Forty‐one critically ill patients without thyroid disease with multiple organ failure who were admitted to the ICU. Measurements and Main Results: The TSH response to TRH was tested within 24 hrs of ICU admission. Blood samples were obtained just before, and at 15, 30, 60, 90, and 120 mins after 500‐&mgr;g injection of synthetic TRH. Triiodothyronine, free‐triiodothyronine, thyroxine, free‐thyroxine and TSH concentrations were measured in the samples obtained just before TRH injection. Acute Physiology and Chronic Health Evaluation (APACHE II) scores and Sepsis scores were calculated based on the data obtained within 24 hrs of ICU admission. Individual variables were compared between survivors and nonsurvivors. The APACHE II scores and Sepsis scores of nonsurvivors were significantly higher than those scores of survivors. The overall occurrence of suppressed TSH response to TRH was 88%. Peak TSH concentration of the TSH response was significantly lower in nonsurvivors than in survivors. Serial measurement of the TSH response showed that nonsurvivors experienced a decrease in peak TSH concentration from 1.55 ± 0.78 to 0.55 ± 0.30 &mgr;IU/mL; in survivors, it increased from 2.10 ± 0.26 to 7.38 ± 1.83 &mgr;IU/mL. Conversely, the basal TSH concentration did not change in either survivors or nonsurvivors. The “severity” of illness of nonsurvivors remained high; their mean APACHE II score varied from 20.0 ± 1.9 to 22.1 ± 1.3 and the mean Sepsis score varied from 20.0 ± 4.3 to 25.4 ± 4.0, while the same scores for survivors decreased significantly ( p < .05): their APACHE II score decreased from 16.2 ± 0.7 to 7.6 ± 2.0 and the Sepsis score went from 14.0 ± 1.9 to 6.0 ± 1.6. Conclusions: In critically ill patients with multiple organ failure, suppression of the TSH response to TRH frequently occurs and correlates with severity of illness and outcome. Our data indicate that measurement of the TSH response is helpful in evaluating the severity of illness and prognosis for critically ill patients. (Crit Care Med 1994; 22:1603–1609)

Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal hysterectomy

Purpose: To assess whether perioperative intravenous administration of flurbiprofen, a non-steroidal anti-inflammatory drug, reduced postoperative pain after abdominal hysterectomy.Methods: Forty-five patients undergoing abdominal hysterectomy were randomly assigned to one of three groups of equal size. A control group (CONT) received a placebo 30 min before and at the end of surgery. The other two groups, PRE and POST, received 1 mg·kg−1 flurbiprofeniv 30 min before and at the end of surgery, respectively. All patients received identical general and epidural anesthesia. Postoperatively, 50 mg diclofenacpr was given for pain relief on patient demand. One of the authors assessed pain using a 10 cm visual analog scale at rest and during coughing at the first request for diclofenac, and at 15, 24, 48, and 72 hr after surgery. The number of times diclofenac was required during the first 24 hr after surgery was also recorded.Results: The number of diclofenac requests in the PRE (1.8±0.4) and POST groups (2.0±0.4) were less than in the CONT group (3.0±0.4). The PRE group showed lower visual analog scale at rest at 15 and 24 hr and on coughing at 24, 48, and 72 hr after surgery than the CONT and POST groups.Conclusion: intravenous 1 mg·kg− flurbiprofen administered during anesthesia reduces postoperative rescue analgesic requirement after abdominal hysterectomy. Moreover, flurbiprofen is more effective when given before than after surgery.RésuméObjectif: Vérifier si l’administration intraveineuse périopératoire de flurbiprofène, un anti-inflammatoire non stéroïdien, réduit la douleur postopératoire d’une hystérectomie abdominale.Méthode: Quarante-cinq patientes devant subir une hystérectomie abdominale ont été réparties au hasard en trois groupes égaux. Un groupe témoin (TEM) a reçu un placebo, 30 min avant et à la fin de l’opération. Les deux autres groupes, PRE et POST, ont reçu 1 mg·kg−1 de flurbiprofèneiv 30 min avant et à la fin de l’intervention, respectivement. Toutes les patientes ont reçu une anesthésie générale et épidurale identique. Après l’intervention, 50 mg de diclofénacpr ont été administrés sur demande comme analgésie. Un des auteurs a évalué la douleur en utilisant une échelle visuelle analogique de 10 cm, au repos et pendant la toux à la première demande de diclofénac et, puis à 15, 24, 48 et 72 h après l’opération. On a aussi noté le nombre de demandes de diclofénac pendant les 24 premières heures postopératoires.Résultats: Les demandes de diclofénac dans les groupes PRE (1,8±0,4) et POST (2,0±0,4) ont été moins nombreuses que dans le groupe TEM (3,0±0,4). Le groupe PRE a donné des scores plus bas à l’EVA au repos à 15 et 24 h et lors de la toux à 24, 48, et 72 h après l’intervention, en comparaison avec les groupes TEM et POST.Conclusion: L’administration intraveineuse de 1 mg·kg−1 de flurbiprofène pendant l’anesthésie réduit les besoins d’analgésie postopératoire à la suite d’une hystérectomie abdominale. De plus, le flurbiprofène est plus efficace lorsqu’on l’adminsitre avant qu’après l’intervention chirurgicale.

Effects of verapamil on spinal anesthesia with local anesthetics.

The primary mode of action of local anesthetics is through sodium channel and axonal conduction blockade.Local anesthetics also have extensive effects on presynaptic calcium channels that must function to stimulate the release of neurotransmitters. Thus, interference with calcium channel conductance may enhance spinal anesthesia with local anesthetics. The present study was designed to investigate the effects of the intrathecal calcium channel blocker, verapamil, on the spinal anesthesia from lidocaine and tetracaine. Male Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters. Tail-flick (TF) and mechanical paw pressure (MPP) tests were used to assess thermal and mechanical nociceptive threshold, respectively. Motor function was assessed using a modified Langermans scale. Intrathecal lidocaine or tetracaine alone showed the prolongation of TF latency, the increase of MPP threshold, and the increase in motor function scale in a time- and dose-dependent manner. Although intrathecal verapamil alone demonstrated neither sensory nor motor block at the doses used (50-200 micro gram), the combination of lidocaine (20, 50, 100, or 200 micro gram) or tetracaine (10, 20, 50, or 100 micro gram) and verapamil (50 micro gram) produced the more potent and prolonged antinociception and motor block when compared with local anesthetics alone. We interpreted these results to indicate that the intrathecal calcium channel blocker, verapamil, potentiates spinal anesthesia with local anesthetics. (Anesth Analg 1995;80:444-8)

Rupture of pulmonary artery induced by balloon occlusion pulmonary angiography

A case of pulmonary artery rupture induced by balloon occlusion pulmonary angiography (BOPA) is reported. A flow-directed pulmonary artery catheter had been inserted for hemodynamic monitoring in a septic shock patient complicated by acute respiratory distress syndrome. To check for pulmonary damage, BOPA was performed immediately after hemodynamic measurement. Just as the hand injection of contrast medium was ending, the patient began to cough and a small amount of hemoptysis was observed. The angiogram showed the extravasation of contrast medium from the distal pulmonary artery to the situation of catheter tip. Pulmonary hemorrhage was controlled with mechanical ventilatory support with 10 cmH2O positive end-expiratory pressure and no specific therapy was required. This complication should be kept in mind and using a power injector to avoid injurious transient high pressure pulse is recommended.

Two minutes of sevoflurane does not improve intubating conditions under vecuronium priming

Sevoflurane has a low blood/gas partit ion coefficient which shortens anesthesia induction and recovery times because of its rapid uptake and elimination [1,2]. Sevoflurane also exerts a strong potentiating effect on neuromuscular block by vecuronium, in approximate proport ion to its inhaled concentration [3]. However, there are no published evaluations of intubating conditions after priming with vecuronium under sevoflurane anesthesia. The present study examined whether sevoflurane administration for 2 min prior to intubation facilitates intubating conditions with vecuronium priming, as reported by Taboada et al. [4].