[Anesthetic Management of a Patient with Double Outlet Right Ventricle and Situs Inversus for Dilatation and Curettage of the Uterus].

A 30-year-old woman with a double outlet right ven- tricle and situs inversus was scheduled for dilatation and curettage of the uterus. We selected intravenous anesthesia which allowed spontaneous respiration, because of the short operation time and the low invasive surgery. We administered dexmedetomidine hydrochloride 1.1 µg · kg⁻¹ · hr⁻¹ and fentanyl (total amount 150 µg, three doses of 50 µg each) during operation. We accomplished anesthesia without appar- ent hemodynamic change or respiratory depression. We should select anesthetic method and anesthetic cautiously, considering patient's state.

The antihyperalgesic effects of intrathecal bupropion, a dopamine and noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.

BACKGROUND: Antidepressants are often used for the treatment of neuropathic pain, and their analgesic effects rely on increased noradrenaline and serotonin levels in the spinal cord. Clinical studies have also shown that bupropion, a dopamine and noradrenaline reuptake inhibitor, has strong efficacy in neuropathic pain; however, the role of spinal cord dopamine in neuropathic pain is unknown. We hypothesized that bupropion inhibits neuropathic pain by increasing noradrenaline and dopamine in the spinal cord. In the present study, we determined the efficacy and underlying mechanisms of intrathecal administration of bupropion in a rat model of neuropathic pain. METHODS: Male Sprague-Dawley rats were anesthetized, and right L5 spinal nerve ligation (SNL) was performed to produce mechanical hyperalgesia of the hindpaw. Withdrawal threshold to a paw pressure test was measured before and after intrathecal administration of bupropion, without or with intrathecal antagonists for α2-adrenoceptors and dopamine D2 receptors. In vivo microdialysis was performed in the dorsal horn of the lumbar spinal cord to measure noradrenaline and dopamine concentrations after intrathecal injection of bupropion. We also measured the noradrenaline and dopamine contents in the ipsilateral dorsal lumbar spinal cord in normal rats and in rats 2, 3, and 4 weeks after SNL. RESULTS: Intrathecal injection of bupropion produced a dose-dependent antihyperalgesic effect (3, 10, 30, and 100 µg, P < 0.001). The effect (30 µg) was dose-dependently reversed by intrathecal pretreatment (15 minutes before bupropion injection) with the α2-adrenoceptor antagonist idazoxan (3, 10, and 30 µg, P < 0.001) and D2 receptor antagonist sulpiride (3, 10, and 30 µg, P < 0.001). Microdialysis revealed that noradrenaline and dopamine concentrations in the spinal dorsal horn were increased after intrathecal injection of bupropion (30 µg, P < 0.001 and P = 0.001, respectively). Furthermore, the noradrenaline and dopamine contents in the spinal dorsal horn were increased 2 weeks after SNL (P < 0.001 and P = 0.044, respectively) and then decreased gradually. CONCLUSIONS: These findings suggest that plasticity of descending inhibitory pathways such as the noradrenaline and dopamine systems contributes to the maintenance of neuropathic pain and that spinal cord noradrenaline and dopamine both play an inhibitory role in neuropathic pain.

CT-guided nerve block: a review of the features of CT fluoroscopic guidance for nerve blocks.

Nerve blocks are an attractive interventional therapy in pain medicine. Several image guidance methods are available to secure the safety, accuracy, and selectivity of the nerve block. Computed tomography (CT) guidance provides a clear view of the vital viscera and vessels that should be avoided by the needle, and accurate placement of the needle tip before neuro-destructive procedures. A recent advance in CT technology is multi-slice CT fluoroscopy, which allows for rapid and easy correction of needle tip placement during insertion. To reduce the radiation dose for both patients and staff, the lowest radiation setting, intermittent quick-check fluoroscopy, and shortening of the planning scan should be used. Preliminary CT scanning with excellent spatial resolution may facilitate the application of CT fluoroscopic guidance to various types of nerve blocks. Here we review celiac plexus and splanchnic nerve blocks, trigeminal nerve block, neurolytic sympathectomy, and spinal intervention performed under CT guidance. Additional large-scale studies are needed to optimize the use of image guidance, especially CT fluoroscopy guidance, for nerve blocks.

An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat.

Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. Male Sprague-Dawley rats underwent spinal nerve ligation (SNL), and the withdrawal threshold to paw pressure was measured. Intraperitoneal injection of milnacipran (3-30mg/kg) produced a dose-dependent antihyperalgesic effect. The effect was reversed by intrathecal injection of the α(2)-adrenoceptor antagonist idazoxan (30µg), but not by various 5-HT receptor antagonists. Paroxetine produced an antihyperalgesic effect only at the highest dose tested (10mg/kg). This effect was reversed by intrathecal injection of both idazoxan and ondansetron (30µg), a 5-HT3 receptor antagonist. Maprotiline produced an antihyperalgesic effect (10 and 30mg/kg), and the effect was reversed by intrathecal idazoxan. In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs.

Location of major vessels in prone-positioned patients undergoing percutaneous lumbar sympathectomy.

INTRODUCTION: The topographic relationship between major vessels and the sympathectomy target is not identical across patients and may not be clear, especially in patients in the prone position. The aim of this study was to provide anatomic data regarding the location of the major vessels (i.e., vena cava and aorta) based on computed tomography (CT) images obtained during lumbar sympathectomy under CT fluoroscopic guidance. METHODS: Thirty-six patients with peripheral arterial occlusive disease or chronic pain syndrome were treated using fluoroscopic CT-guided percutaneous lumbar sympathectomy between April 2006 and March 2010. We analyzed the shortest distances between the sympathectomy target and the major vessels, and the relationship between the location of the major vessels and the vertebral anterior line using CT images obtained during the procedure. RESULTS: At the L3 level, the shortest distances from the right side target to the inferior vena cava were significantly shorter than the other distances (P < 0.05). In 11 of 36 patients (30.6%), the IVC was located dorsal to the vertebral anterior line at the L3 level. CONCLUSION: Needle insertion for right side sympathectomy at the L3 level may present a higher risk of major vessel puncture than sympathectomy at other sites. CT guidance is recommended for lumbar sympathectomy to reduce the risk of vascular puncture.

Lack of analgesic efficacy of spinal ondansetron on thermal and mechanical hypersensitivity following spinal nerve ligation in the rat.

The balance between descending inhibition and facilitation is thought to be disturbed in chronic pain states. Increased facilitation by spinally released serotonin has been suggested by demonstration that mechanically evoked neuronal responses of wide dynamic range neurons are inhibited by 5-HT3 receptor antagonists in rats following spinal nerve ligation (SNL) but not sham operation. Despite these physiologic data, the effects of spinal 5-HT3 receptor blockade on behavioral hypersensitivity and neurochemical alterations in spinal serotonergic system have not been thoroughly investigated following spinal nerve ligation in the rat. To test this, we acutely injected intrathecal ondansetron in rats between 14 and 30 days after SNL and assessed effects on thermal and mechanical hypersensitivity. We also determined the density of serotonergic nerve fibers, serotonin content and the levels of 5-HT3 receptors within the spinal cord at this time point. Intrathecal ondansetron (1, 3, 10, 30, and 100microg) produced no effect on behavioral measures of thermal or mechanical hypersensitivity whereas intrathecal morphine (1microg) and gabapentin (200microg) partially reversed thermal and mechanical hypersensitivity following SNL. In addition, SNL did not alter the density of serotonergic fibers or 5-HT3 receptor immunoreactivity or spinal tissue content of 5-HT within the dorsal horn. These results do not support anatomic plasticity of descending serotonergic pathways or tonic 5-HT3 receptor activity in maintaining hypersensitivity after nerve injury and in contrast to previous studies fail to demonstrate an anti-hypersensitivity effect of intrathecal injection of the 5-HT3 receptor antagonist ondansetron. Importantly, behavioral measures of mechanical hypersensitivity assess threshold responses whereas physiological studies of mechanically evoked neuronal responses involve application of suprathreshold stimuli. Thus, suprathreshold or more intense stimuli may be necessary to recruit descending serotonergic facilitatory drive required to observe the inhibitory effects of ondansetron on spinal neuronal excitability and behavioral hypersensitivity.

[Woman with mitochondrial encephalomyopathy who died of cardiogenic shock after surgery].

We describe a case of 39-year-old woman with mitochondrial encephalomyopathy who underwent radical operation of proctoptosis under general anesthesia. She had chronic renal failure, hypertrophic cardiomyopathy, WPW syndrome, and some other complications with this disease, and her ADL had been decreasing. Since there are few reports about mitochondrial encephalomyopathy and the anesthesia, we did not know the effect of spinal anesthesia or muscle relaxant on this disease, and we selected general anesthesia with laryngeal mask. Operation and general anesthesia went on without any accident; however, on the 4th postoperative day, she died of cardiogenic shock. Autopsy was not performed. We came to a conclusion that there is little relation between her death and general anesthesia, and she died of this disease itself. Of course, general anesthesia might have some effects on her death, but it is difficult to establish the relation of general anesthesia and her death. Great care should be taken for the patient with mitochondrial encephalomyopathy during and after surgery.

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 microg) produced dose-dependent antihypersensitivity effects. The effect lasted 6 h after the 30-microg injection. Doses of 30 microg or less produced no abnormal behavior. The peak antihypersensitivity effect of 10 microg of milnacipran was blocked by intrathecal pretreatment with antagonists of the alpha(2)-adrenoceptor (idazoxan; 30 microg) or 5-HT receptors (methysergide; 30 microg). Intrathecal pretreatment with 30 microg of naloxone, a mu-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.

The nociceptive mechanism of 5-hydroxytryptamine released into the peripheral tissue in acute inflammatory pain in rats.

The present study examined the contribution of 5-hydroxytryptamine (5-HT) to acute peripheral inflammatory pain in rats. We used formalin test in this study. After formalin injection into the rat hind paw, biphasic pain-related behavior (phases 1 and 2) was observed. A microdialysis study revealed that 5-HT was released into the formalin injection site in a formalin concentration-dependent manner (1.25-5%), and its peak time was 18min after the injection. Previous studies suggest that peripheral 5-HT2 receptors are involved in inflammatory pain. Therefore, we next examined whether 5-HT2A and 5-HT2C receptors are involved, and from where 5-HT is released in the formalin test. Local pretreatment with a selective 5-HT2A receptor antagonist, ketanserin, and selective 5-HT2C receptor antagonists, RS102221 and SB242084, inhibited the number of flinches in early part of phase 2 (phase 2A) of the formalin test in a dose-dependent manner. Peripheral pretreatment with sodium cromoglycate (cromolyn), a mast cell membrane stabilizer, completely suppressed 5-HT release and inhibited phase 2 responses of the formalin test. These drugs inhibited c-fos expression in the superficial layer of the spinal dorsal horn of segments L4-5 at 2h after formalin injection. These results indicate that 5-HT released into peripheral tissue and its receptors, 5-HT2A as well as 5-HT2C, at the periphery have an important role in pain-related behaviors during acute peripheral inflammation.

Gabapentin acts within the locus coeruleus to alleviate neuropathic pain.

BACKGROUND: Gabapentin recruits descending inhibition to produce analgesia after nerve injury, but whether this is a local action in the brainstem is unknown. The authors hypothesized that gabapentin activates noradrenergic neurons in the locus coeruleus (LC) by a local action. METHODS: Male rats underwent L5-L6 spinal nerve ligation (SNL) and received drugs by intra-LC or systemic routes for behavior testing, immunohistochemistry in the LC, and microdialysis in the spinal dorsal horn. In other studies, brainstem slices from normal and SNL animals were used for immunohistochemistry. RESULTS: SNL increased phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB)-expressing nuclei bilaterally in the LC, and increased noradrenaline release in the spinal dorsal horn. Gabapentin, whether in isolated brainstem slices or in conscious or anesthetized animals, increased pCREB-expressing nuclei in the LC. The net increase in pCREB expression by gabapentin did not differ between normal and SNL conditions. This gabapentin-induced pCREB activation in LC neurons was abolished by an AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Intra-LC-injected gabapentin reduced hypersensitivity in SNL rats in a dose-dependent manner. Both intra-LC coadministration of CNQX and intrathecal administration of the alpha2-adrenoceptor antagonist idazoxan blocked antihypersensitivity by intra-LC gabapentin. Intravenous gabapentin induced noradrenaline release in the spinal dorsal horn. The net amount of noradrenaline release by gabapentin is larger in SNL rats compared with the normal condition, although the percentage increases from the baseline were the same. CONCLUSIONS: These results suggest that gabapentin acts directly in the brainstem via a glutamate-dependent mechanism to stimulate descending inhibition to produce antihypersensitivity after peripheral nerve injury.