Keiji Ishizaki

Epidural block with mepivacaine before surgery reduces long-term post-thoracotomy pain

PurposeTo examine the effect of continuous epidural block initiated before thoracic surgery upon early and long-term postoperative pain.MethodsIn a double-blind study, 70 patients scheduled for thoracic surgery under general anesthesia were assigned randomly to receive continuous epidural block with mepivacaine 1.5% initiated either 20 min before surgical incision (Pre group) or at completion of surgery (Post group). In both groups the initial dose was 4 ml, followed by a continuous infusion at 4 ml·hr−1 until 72 hr after operation. Indomethadn suppositories, 50 mg, were administered on request as supplementary analgesics. Visual analogue scale at rest was assessed four hours after operation, and then every 24 hr after operation on postoperative days 1 through 7, and also days 14 and 30. At three and six months after operation, all patients were interviewed by telephone with respect to postoperative pain. The most severe pain was assessed using modified numerical rating scale.ResultsBy a visual analogue scale, postoperative pain was less in the Pre group than in the Post group at four hours, two and three days after operation (P < 0.05). By a numerical rating scale six months after operation, pain was less in the Pre group than in the Post group (P = 0.015). The percentage of pain-free patients was higher in the Pre group than in the Post group at three (P = 0.035) and six (P = 0.0086) months after operation.ConclusionContinuous epidural block initiated prior to surgery may reduce long-term post-thoracotomy pain.RésuméObjectifExaminer l’effet d’un blocage épidural continu, amorcé avant une intervention chirurgicale thoracique, sur la douleur postopératoire précoce et de long terme.MéthodeLétude à double insu a porté sur 70 patients qui devaient subir une opération thoracique sous anesthésie générale. Répartis au hasard, ils ont reçu un blocage épidural continu avec de la mépivacaïne à 1,5 %, administrée soit 20 min avant l’incision chirurgicale (groupe Pré), soit à la fin de l’intervention (groupe Post). Pour tous, la dose initiale a été de 4 ml suivie d’une perfusion continue à 4 ml·hr−1 jusqu’à 72 h après l’opération. Des suppositoires de 50 mg d’indométhacine ont été administrés sur demande pour compléter l’analgésie. La douleur a été évaluée au repos selon l’échelle visuelle analogique, 4 h après l’opération et puis à toutes les 24 h des jours 1 à 7 et aussi les jours 14 et 30. Trois mois et six mois après l’opération, tous les patients ont été interrogés par téléphone au sujet de la douleur postopératoire. La douleur la plus sévère a été évaluée en utilisant une échelle d’estimation numérique modifiée.RésultatsSelon l’échelle visuelle analogique, la douleur postopératoire était plus faible chez les patients du groupe Pré que chez ceux du groupe Post à 4 h, deux et trois jours après l’opération (P < 0,05). Selon une échelle d’estimation numérique, la douleur était moins intense chez les patients du groupe Pré que chez ceux du groupe Post (P = 0,015) six mois après l’opération. Le pourcentage de patients sans douleur était plus élevé dans le groupe Pré que dans le groupe Post à trois mois (P = 0,035) et à six mois (P = 0,0086) après l’opération.ConclusionLe blocage épidural continu amorcé avant l’intervention chirurgicale peut réduire la douleur qui se prolonge après une thoracotomie.

Effects of 5-HT2 and 5-HT3 receptors on the modulation of nociceptive transmission in rat spinal cord according to the formalin test

We used the formalin test to clarify the 5-hydroxytryptamine (5-HT) receptor subtypes involved in the modulation of spinal nociceptive transmission in rats. Intrathecal administration of a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetraline (8-OH-DPAT; 1, 10, and 30 microg), or a 5-HT1B receptor agonist, 1, 4-dihydro-3-(1, 2, 3, 6-tetrahydro-4-pyridinyl)-5H-pyrrol (3, 2-b) pyridin-5-one (CP 93129; 1 and 10 microg), produced no significant change in the number of flinches. A 5-HT(2) receptor agonist, (+/-)-2, 5-dimethoxy-4-iodoamphetamine (DOI; 10, 30, and 100 microg), and a 5-HT3 receptor agonist, 2-methyl-5-HT (100 and 300 microg), produced dose-dependent decreases in the number of flinches in phases 1 (1 to 6 min) and 2 (10 to 61 min) of the test. The antinociceptive effects of DOI and 2-methyl-5-HT were antagonized by intrathecal pretreatment with a 5-HT2 receptor antagonist, ketanserin, and a 5-HT3 receptor antagonist, 3-tropanyl-3, 5-dichlorobenzoate (MDL-72222), respectively. These results suggest that 5-HT2 and 5-HT3 receptors in the spinal cord mediate antinociception to chemical stimuli.

Antiallodynic effect of intrathecally administered 5-HT2 agonists in rats with nerve ligation

&NA; We examined the antiallodynic effect of intrathecally administered serotonin receptor agonists including 5‐HT1A, 5‐HT1B, 5‐HT2 and 5‐HT3 receptor subtypes in a rat model using spinal nerve ligation at L5 and L6. Administration of the 5‐HT2 receptor agonist, &agr;‐methyl‐5‐hydroxytryptamine maleate (&agr;‐m‐5‐HT; 3–100 &mgr;g) or (±)‐1‐(4‐iodo‐2,5‐dimethoxyphenyl)‐2‐aminopropane hydrochloride (DOI; 10–100 &mgr;g), showed dose‐dependent antiallodynic actions with no associated motor weakness. The antiallodynic action of &agr;‐m‐5‐HT was more potent than that of DOI. The effects of 5‐HT2 agonists on tactile allodynia were reversed by intrathecal pretreatment with the selective 5‐HT2 antagonist ketanserin and with the mixed 5‐HT1 and 5‐HT2 antagonist methysergide. Neither the mixed 5‐HT1A and 5‐HT1B antagonist cyanopindolol nor the selective 5‐HT3 antagonist MDL72222 attenuated antiallodynic effects induced by 5‐HT2 agonists. In contrast, the selective 5‐HT1A agonist 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin hydrobromide (8‐OH‐DPAT; 1–50 &mgr;g), the 5‐HT1B agonist 5‐methoxy‐3‐(1,2,5,6‐tetrahydro‐4‐pyridinil)‐1H‐indol (RU‐24969; 10–100 &mgr;g) and the 5‐HT3 agonist 2‐methyl‐5‐hydroxytryptamine maleate (2‐m‐5‐HT; 30–300 &mgr;g) all lacked significant antiallodynic action with intrathecal administration. These results indicate that the 5‐HT2 receptor plays an essential role in spinal suppression of neuropathic pain by 5‐HT.

The long lasting effects of peripheral nerve blocks for trigeminal neuralgia using a high concentration of tetracaine dissolved in bupivacaine

The management of trigeminal neuralgia in older patients who do not want neurolytic block and/or surgical treatment may be problematic. This paper describes three patients who had first and/or second division trigeminal neuralgia. The analgesic effects of infraorbital nerve block using 0.5% bupivacaine or 1% mepivacaine dissipated within a few days, however, the effects of nerve blocks using 4% tetracaine dissolved in 0.5% bupivacaine continued for more than 3 months. Hypesthesia was observed in two patients within a week following the block, but sensory level returned to normal within 2 weeks and there were no further complications in any patient.

The effect of intrathecal magnesium sulphate on nociception in rat acute pain models.

We examined the antinociceptive effect of intrathecally administered magnesium sulphate (MgSO4) in rats, using acute pain models including mechanical pressure, heat and subcutaneous formalin injection. According to the locomotion test 10 μl of 6.2% MgSO4 did not produce motor paralysis. At the same dose, responses to pressure and heat were intact, compared with controls given saline. MgSO4 produced depression of pain responses only after the first 10 min in the formalin test. Our studies indicated that MgSO4 did not show remarkable antinociceptive effects in acute pain models.

Antinociception in rat by sarpogrelate, a selective 5-HT2A receptor antagonist, is peripheral

The antinociceptive effect of sarpogrelate, a new selective 5-hydroxytriptamine (5-HT)(2A) receptor antagonist, in the formalin test was examined in rats. Sarpogrelate was administered intraperitoneally, locally (subcutaneously at the formalin test site) or intrathecally 10 min before formalin injection. Intraperitoneal (1-100 mg/kg) and local (0.01-1 mg) administration of sarpogrelate suppressed flinching behavior in both phases 1 (0-9 min) and 2 (10-60 min) in a dose-dependent manner. Intraperitoneal (100 mg/kg) and local (1 mg) injection 7 min after formalin injection reduced phase 2 flinches to the same degree as with the pre-treatment. Intrathecal administration (1-100 microg) showed no antinociceptive action, and facilitated phase 2 flinches at 10 microg. The plasma concentration of sarpogrelate after local administration of 1 mg was lower than after intraperitoneal administration of 10 mg/kg, although local administration produced more potent antinociception. The data imply that the antinociceptive effect of sarpogrelate results mainly from an action at peripheral sites.

Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats

PurposeWe studied the effects of intrathecal administration of an N-methyl-D-aspartate (NMDA) receptor antagonist and an antagonist of the glycine site of the NMDA receptor on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats, and on locomotor activity in conscious rats.MethodsIn Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after the administration of saline (control group); the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)pro-pyl-1-phosponic acid(CPP) at 0.01, 0.1, and 1.0 nM; and the selective antagonist of the glycine site on the NMDA receptor complex 7-chlorokynurenic acid (7CKA) at 0.1, 1.0, and 10 nM. After measurement of MAC following administration of the antagonist, the equipotent reversal dose of NMDA or D-serine was administered. The rats were examined for the presence of locomotor dysfunction by intrathecal administration of NMDA receptor antagonists, NMDA and D-serine in conscious rats. All of the experiments were performed using randomization and masking of drugs.ResultsCPP at 0.1 and 1.0 nM decreased the MAC of isoflurane by 9.9–17.6% (P < 0.05). 7CKA at 1.0 and 10 nM reduced MAC from 10.5–15.5% (P < 0.05). Intrathecal administration of NMDA or D-serine reversed the decreases in MAC to control values. Locomotor activity was not changed.ConclusionsWe believe that NMDA receptor plays an important role in determining the MAC of isoflurane in the spinal cord.RésuméObjectifÉtudier l’influence de l’administration d’un antagoniste du récepteur N-méthyl-D-aspartate (NMDA) et d’un antagoniste du site glycine du NMDA sur la concentration anesthésique alvéolaire minimum (MAC) de l’isoflurane chez le rat anesthésié et sur l’activité locomotrice chez le rat conscient.MéthodesChez des rats Wistar porteurs d’un cathéter sousarachnoïdien implantés, nous avons déterminé le MAC après l’administration de soluté physiologique (groupe contrôle); de l’antagoniste compétitif du récepteur NMDA. l’acide 3-(2-car-boxyperazine-4-yl) propyl-l-phosphonique (CPP) à 0,01, 0,1 et 1,0 nM; et l’antagoniste sélectif du site glycine du complexe récepteur NMDA l’acide 7-chlorokynurénique (7CKA) à 0,1 1,0 et 10 nM. Après la mesure du MAC à la suite de l’administration de l’antagoniste, des doses de neutralisation équipotentes de NMDA ou de D-sérine ont été administrées. La présence d’un dysfonctionnement locomoteur a été recherchée par l’administration sousarachoïdienne de l’antagoniste du récepteur NMDA, de NMDA et de D-sérine chez les rats conscients. Toutes les expériences ont été conduites aléatoirement et avec masquage des produits.RésultatsLe CPP à 0,1 et 1,0 nM a diminué le MAC de l’isoflurane de 9,9–17.6% (P < 0,05). Le 7CKA à 1,0 et 10 nM a réduit le MAC de 10,5–15,5% (P < 0,05). Administration sousarachnoïdienne de NMDA ou de D-sérine a ramené le MAC aux valeurs de contrôle. L’activité locomotrice n’a pas changé.ConclusionNous croyons que le récepteur NMDA joue au niveau de la moelle épinière un rôle important dans la délimination du MAC.

The effect of intrathecal administration of magnesium sulphate in rats

Somatosensory evoked potential, locomotion and vocalisation upon tail pinch in rats was studied in order to determine whether intrathecal magnesium sulphate administration causes spinal anaesthesia. In Wistar rats with indwelling intrathecal catheters, cortical somatosensory evoked potential was recorded following stimulation via electrodes inserted into the hind paw under chloral hydrate anaesthesia before and after intrathecal administration of 10 μl of either magnesium sulphate (12.3% or 24.6%) or lignocaine (4% or 8%). Locomotion and vocalisation after tail pinch were tested following intrathecal administration of the same two drugs in conscious rats. Somatosensory evoked potential amplitude was diminished after administration of lignocaine (p < 0.05) but did not change after magnesium sulphate. Latency of P1 was increased by lignocaine and by magnesium sulphate 12.3% (p < 0.05). Although lower extremity paralysis was observed in both groups, its duration with magnesium sulphate was much longer than with lignocaine. Vocalisation was recognised after magnesium sulphate 12.3%, but was not observed after lignocaine 8% during paralysis (p < 0.05). We believe that magnesium sulphate caused motor paralysis, but not complete analgesia.

Hyperventilation after tourniquet deflation prevents an increase in cerebral blood flow velocity

PurposeIn this study we examined whether normocapnia maintained by hyperventilation after lower limb tourniquet deflation prevents an increase in cerebral blood flow velocity.MethodsThirteen patients, undergoing elective orthopedic surgery, requiring a pneumatic tourniquet around the lower extremity, were divided into two groups. In group I, ventilation was controlled at tidal volume of 10 mL·kg−1 and respiratory rate of eight per minute after tourniquet release. In group 2, ventilation was controlled to maintain PETCO2 between 30 and 35 mmHg after tourniquet release. Arterial blood pressure, heart rate, peak and mean middle cerebral artery (MCA) flow velocity, and arterial blood gas were measured every minute for ten minutes after tourniquet release. The MCA blood flow velocity was measured using Transcranial Doppler ultrasonography (TCD).ResultsIn group I, the maximum peak MCA flow velocity was 53 ± 6 cm·sec−1 (50 % ± 6% increase compared with pre-release value), and achieved 3 ± 0.4 min after tourniquet release. In group 2, there was no increase either in mean or peak MCA velocity after tourniquet release.ConclusionsNormocapnia maintained by hyperventilation after tourniquet deflation prevents an increase in cerebral blood flow velocity.RésuméObjectifVérifier si la normocapnie maintenue par l’hyperventilation après le dégonflage d’un garrot autour du membre inférieur empêche l’augmentation de la vitesse du flux sanguin cérébral.MéthodeTreize patients, admis pour une chirurgie orthopédique nécessitant un garrot pneumatique autour du membre inférieur, ont été répartis en deux groupes. Après le relâchement du garrot, on note que: dans le Groupe I, la ventilation était maintenue au volume courant de 10 ml·kg−1 et la fréquence respiratoire à huit par minute; dans le Groupe 2, la ventilation était contrôlée pour maintenir la PETCO2.entre 30 et 35 mmHg: la tension artérielle, la fréquence cardiaque, la vitesse moyenne et maximale du flux de l’artère cérébrale moyenne (ACM) et les gaz du sang artériel étaient mesurés à chaque minute pendant dix minutes. La vitesse du flux de l’ACM a été mesurée par échographie-Doppler transcrânienne (DTC).RésultatsDans le Groupe I, la vitesse maximale du flux de l’ACM a été de 53 ± 6 cm·sec−1 (50 % ± 6 % d’augmentation en comparaison des valeurs précédant la libération du garrot), et a été atteinte 3 ± 0,4 min après le garrot. Dans le Groupe 2, il n’y a pas eu d’augmentation de la vitesse moyenne ou maximale du flux de l’ACM après le garrot.ConclusionLa normocapnie maintenue par l’hyperventilation après le dégonflage du garrot peut empêcher une augmentation de la vitesse du flux sanguin cérébral.

Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats.

Background: Intravenous administration of N‐methyl‐D‐aspartate (NMDA) receptor antagonists and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor antagonists reportedly reduce the minimum alveolar anaesthetic concentration (MAC) for inhalation anaesthetics. If pain perception can be prevented by the intrathecal administration of antinociceptive receptor antagonists, these agents may reduce the requirements for inhalation anaesthetics. We studied the effect of intrathecal administration of an AMPA/kainate receptor antagonist, a metabotropic glutamate (mGlu) receptor antagonist and co‐administration of NMDA and a neurokinin‐1(NK‐1) receptor antagonist drugs at low doses on the MAC.