Chih-Shung Wong

National Taipei University of Nursing Sciences, T’ai-pei, Taipei, Taiwan

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Publications (160)280.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Glutamate and oxidative stress play important roles after subarachnoid hemorrhage (SAH). The ability to modulate glutamate transporter 1 (GLT-1) and the antioxidative effect of rosiglitazone have been demonstrated. We investigated the neuroprotective effect of rosiglitazone after SAH.
    Neurocritical Care 07/2014; · 3.04 Impact Factor
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    ABSTRACT: As known, long-term morphine infusion leads to tolerance. We previously demonstrated that both co-infusion and post-administration of ultra-low dose (±)-naloxone restores the antinociceptive effect of morphine in morphine-tolerant rats. However, whether the mechanism of the action of ultra-low dose (±)-naloxone is through opioid receptors or not. Therefore, in the present study, we further investigated the effect of ultra-low dose (+)-naloxone, it does not bind to opioid receptors, on the antinociceptive effect of morphine. Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one catheter was connected to a mini-osmotic pump, used for morphine (15 μg/h), ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone (15 pg/h) or saline (1 μl/h) infusion for 5 days. On day 5, either ultra-low dose (+)-naloxone (15 pg) or saline (5 μl) was injected via the other catheter immediately after discontinued morphine or saline infusion. Three hours later, morphine (15 μg in 5 μl saline) or saline were given intrathecally. All rats received nociceptive tail-flick test every 30 min for 120 min after morphine challenge at different temperature (45∼52 °C, respective). Our results showed that, both co-infusion and post-treatment of ultra-low dose (+)-naloxone with morphine preserves the antinociceptive effect of morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone further enhances the antinociceptive effect of morphine. This study provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant for patients who need long-term opioid administration for pain management.
    Journal of the Formosan Medical Association 12/2013; · 1.00 Impact Factor
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    ABSTRACT: Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. We designed this investigation to examine whether ultra-low dose naloxone administered alone or in combination with morphine could alter the concentration of the excitatory amino acids (EAAs) glutamate and aspartate, as well as the expression of tumor necrosis factor-α (TNF-α) and its receptors (TNFR1 and TNFR2) in the spinal cord dorsal horn of rats with partial sciatic nerve transection (PST). Male Wistar rats underwent intrathecal catheter implantation for drug delivery and were divided in 7 groups: sham-operated + saline (sham), PST + saline (S), PST + 15 ng naloxone (n), PST + 15 µg naloxone (N), PST + 10 µg morphine (M), PST + 15 ng naloxone + 10 µg morphine (Mn), PST + 15 µg naloxone + 10 µg morphine (MN). Thermal withdrawal latency and mechanical withdrawal threshold, TNF-α and TNFR expression in the spinal cord and dorsal root ganglia, and EAAs glutamate and aspartate concentration in cerebrospinal fluid dialysates were measured. Ten days after PST, rats developed hyperalgesia (P < 0.0001) and allodynia (P < 0.0001), and increased TNF-α (P < 0.0001) and TNFR1 expression (P = 0.0009) were measured in the ipsilateral spinal cord dorsal horn. The antihyperalgesic and antiallodynic effects of morphine (10 μg) were abolished by high-dose naloxone (15 μg; P = 0.0031) but enhanced by ultra-low dose naloxone (15 ng; P = 0.0015), and this was associated with a reduction of TNF-α (P < 0.0001) and TNFR1 (P = 0.0009) expression in the spinal cord dorsal horn and EAAs concentration (glutamate: P = 0.0001; aspartate: P = 0.004) in cerebrospinal fluid dialysate. Analysis of variance (ANOVA) or Student t test with Bonferroni correction were used for statistical analysis. Ultra-low dose naloxone enhances the antihyperalgesia and antiallodynia effects of morphine in PST rats, possibly by reducing TNF-α and TNFR1 expression, and EAAs concentrations in the spinal dorsal horn. Ultra-low dose naloxone may be a useful adjuvant for increasing the analgesic effect of morphine in neuropathic pain conditions.
    Anesthesia and analgesia 12/2013; 117(6):1493-1502. · 3.08 Impact Factor
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    ABSTRACT: Object Baicalein has been shown to offer neuroprotection in the ischemic brain, but its effect in subarachnoid hemorrhage (SAH) is unknown. The authors used a double-hemorrhage model to study the role of early baicalein treatment in SAH. Methods Subarachnoid hemorrhage was induced in male Wistar rats through a repeat injection of autologous blood at a 48-hour interval. Rats subjected or not subjected to SAH received a 30-mg/kg baicalein injection 3 hours after SAH and daily for 6 consecutive days, and results were compared with those obtained in vehicle-treated control rats. Mortality of the rats was recorded. Neurological outcome was assessed daily. Cerebrospinal fluid dialysates were collected and examined for glutamate concentrations. Cerebral vasospasm (CVS), brain water content, neuron variability, expression of glutamate transporter-1 (GLT-1), immunoreactivity of astrocyte, and level of malondialdehyde, activities of superoxide dismutase (SOD), and catalase in brain tissues content were determined on post-SAH Day 7. Results Mortality rate, neuronal degeneration, brain water content, and CVS were decreased and neurological function improved in the baicalein-treated rats. Baicalein increased astrocyte activity and preserved GLT-1, which attenuated the glutamate surge after SAH. Baicalein also provided antioxidative stress by preserving activities of SOD and catalase and decreased malondialdehydelevel after SAH. The glutamate, body weight, neurological scores, and glial fibrillary acidic protein activity were significantly correlated. The CVS was correlated with neuronal degeneration, and GLT-1 was correlated with oxidative stress. Conclusions Early baicalein treatment attenuated CVS and limited neurological injury following SAH. These data may indicate clinical utility for baicalein as an adjunct therapy to reduce brain injury and improve patient outcomes.
    Journal of Neurosurgery 05/2013; · 3.15 Impact Factor
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    ABSTRACT: BACKGROUND/PURPOSE: In a recent study, we found that baicalin exhibited a potent analgesic effect on carrageenan-evoked thermal hyperalgesia. The underlining mechanisms may be associated with inhibition of inflammatory mediator overproduction, including proinflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). In the present study, we examined the effect of baicalin on the antinociceptive effect of morphine and histone deacetylase 1 (HDAC1) expression in the spinal cord dorsal horn in neuropathic pain rats. METHODS: Neuropathic pain was induced by tight ligation of the left L5 spinal nerve of the rats. An intrathecal catheter was implanted for drug administration. Nociception was assessed by using the plantar test with the Hargreaves radiant heat apparatus, and the von Frey test with the dynamic plantar anesthesiometer. Spinal cords were removed for histone acetyl-H3 and HDAC1 western blot analysis at the end of the nociceptive assessment. RESULTS: The results showed that hyperalgesia and allodynia were observed in the spinal nerve ligated (SNL) left hindlimb; it was companied by histone-H3 deacetylation and HDAC1 overexpression on the ipsilateral side of the spinal cord dorsal horn. Intrathecal injection of baicalin (10 μg) significantly attenuated the allodynia and hyperalgesia, and enhanced the antinociceptive effect of morphine (15 μg). Moreover, baicalin reversed the histone-H3 acetylation and suppressed HDAC1 expression on the ipsilateral side of the spinal cord dorsal horn of SNL rats. CONCLUSION: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.
    Journal of the Formosan Medical Association 05/2013; · 1.00 Impact Factor
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    ABSTRACT: A tourniquet is commonly used in limb surgery. Tourniquet inflation after a period of time may produce painful sensation. While the mechanisms of tourniquet-induced pain are still unknown, two components, pressure and ischemia, have been proposed. In this study, in vivo microdialysis was used to detect changes in intrathecal glutamate, an excitatory amino acid highly relevant to pain transmission, following hindlimb tourniquet application and femoral artery occlusion in the rat. Male Wistar rats were used. For the tourniquet study, 6 rats of the study group received 30 minutes right hindlimb tourniquet inflation and another 6 rats as the control group received only tourniquet application without inflation. In the femoral artery occlusion study, 6 rats of the study group received 30 minutes right femoral artery occlusion and another 6 rats as the control group received only sham operation without femoral artery occlusion. Cerebrospinal fluid dialysates were collected prior to, during, and after tourniquet application or femoral artery occlusion. Glutamate was measured by HPLC. A significant increase in intrathecal glutamate release was found during the tourniquet inflation period, and it returned to baseline after tourniquet deflation. No change of glutamate release was noted during femoral artery occlusion or after femoral artery reperfusion. The intrathecal glutamate release was increased by the hindlimb tourniquet inflation, but not influenced by femoral artery occlusion in the rat.
    Journal of the Formosan Medical Association 05/2013; 112(5):259-62. · 1.00 Impact Factor
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    ABSTRACT: The purpose of this preliminary study was to examine whether collateral meridian (CM) therapy was feasible in treating knee osteoarthritis (OA) pain. Twenty-eight patients with knee OA and knee pain were randomly allocated to 2 groups. The CM group patients received CM therapy, whereas the control patients received placebo treatment for knee pain relief. Patients in the CM group received 2 CM treatments weekly for 3 weeks. The outcome measures were pain intensity on a visual analog scale, and knee function was determined using the Western Ontario and McMaster Universities Osteoarthritis Index. In the CM group, the posttreatment visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were lower than those of the control group; a significant reduction in pain intensity (P = .02, P = .01, respectively) and improvement in knee function (P = .04, P = .03, respectively) were shown in the CM group at the second and third week. Collateral meridian therapy may be feasible and effective for knee OA pain relief and knee function recovery. Therefore, additional randomized control trials are warranted.
    Journal of manipulative and physiological therapeutics 01/2013; 36(1):51-6. · 1.06 Impact Factor
  • Ching-Hui Shen, Ru-Ying Tsai, Chih-Shung Wong
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    ABSTRACT: Opioids have been used as potent analgesics in clinics for decades; however, their long-term administration leads to tolerance. Two possible mechanisms for drug tolerance are postulated as within-system and between-systems adaptation. The within-system tolerance is involved in the signal transduction of opioid receptors, including downregulation of opioid receptors, uncoupling of G-protein from opioid receptors, and β-arrestin recruitment to opioid receptors, which causes receptor desensitization and internalization/endocytosis. The between-systems tolerance comprehends the glutamatergic receptor system and glial activation with the release of proinflammatory cytokines, and thus the analgesic effect of morphine is reduced. Tumor necrosis factor-α (TNF-α) is a vital proinflammatory cytokine and exerts either a neurotoxic or neuroprotective effect on different diseases of the central nervous system. TNF-α has also been demonstrated to correlate with neuronal plasticity via activation of spinal glial cells and enhancement of glutamatergic transmission. Previous studies had revealed an increased expression of TNF-α in morphine tolerance. This review article focuses on the role of TNF-α in neuroinflammation and the glutamatergic receptor system in morphine tolerance. It may provide another adjuvant therapy for morphine tolerance, which extends the effectiveness of opioids in clinical pain management.
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists. 12/2012; 50(4):178-82.
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    ABSTRACT: An intravenous bolus of fentanyl often induces a cough reflex. This study investigates whether priming with rocuronium can effectively attenuate fentanyl-induced coughing. The study involved 260 participants, aged between 18 and 80 years of age, who were undergoing various elective surgeries. They were randomly assigned to two groups. Patients in the study group (the rocuronium group) were treated with intravenous (IV) 0.06 mg/kg rocuronium, whereas those in the control group were treated with the same volume of normal saline. Fentanyl (1.5 μg/kg IV, given over 2 seconds) was administered 30 seconds after the injection of rocuronium or normal saline. We recorded the number of coughs for 1 minute after the fentanyl injection. Patients in the rocuronium group showed a significantly lower incidence of coughing (8.5% vs. 23.1%, in the control group; p < 0.05) and a milder severity of cough in comparison with the patients in the control group. Pretreatment with IV rocuronium (0.06 mg/kg) suppressed the cough reflex induced by fentanyl. Therefore, priming with rocuronium may be a clinically useful method for preventing fentanyl-induced cough.
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists. 12/2012; 50(4):147-9.
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    ABSTRACT: We previously demonstrated that intrathecal IL-1β caused thermal hyperalgesia in rats. This study was conducted to examine the effects and cellular mechanisms of glial inhibitors on IL-1β-induced nociception in rats. The effects of minocycline (20 μg), fluorocitrate (1 nmol), and SB203580 (5 μg) on IL-1β (100 ng) treatment in rats were measured by nociceptive behaviors, western blotting of p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) expression, cerebrospinal fluid nitric oxide (NO) levels, and immunohistochemical analyses. The results demonstrated that intrathecal IL-1β activated microglia and astrocytes, but not neurons, in the dorsal horn of the lumbar spinal cord, as evidenced by morphological changes and increased immunoreactivity, phosphorylated p38 (P-p38) MAPK, and iNOS expression; the activation of microglia and astrocytes peaked at 30 min and lasted for 6 h. The immunoreactivities of microglia and astrocytes were significantly increased at 30 min (6.6- and 2.7-fold, respectively) and 6 h (3.3- and 4.0-fold, respectively) following IL-1β injection, as compared with saline controls at 30 min (all P < 0.01). IL-1β induced P-p38 MAPK and iNOS expression predominantly in microglia and less in astrocytes. Minocycline, fluorocitrate, or SB203580 pretreatment suppressed this IL-1β-upregulated P-p38 MAPK mainly in microglia and iNOS mainly in astrocytes; minocycline exhibited the most potent effect. Minocycline and fluorocitrate pretreatment abrogated IL-1β-induced NO release and thermal hyperalgesia in rats. In conclusion, minocycline, fluorocitrate, and SB203580 effectively suppressed the IL-1β-induced central sensitization and hyperalgesia in rats. © 2012 Wiley Periodicals, Inc.
    Glia 09/2012; 60(12):2004-17. · 5.07 Impact Factor
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    ABSTRACT: Epigenetic reprogramming may have a possible role in neuropathic pain development; the present study examined the global patterns of lysine histone modification. In this serial study we analyzed the levels of histone 3 lysine 4 monomethylation, histone 3 lysine 4 dimethylation, and histone 3 lysine 9 trimethylation in pertussis toxin (PTX)-induced thermal hyperalgesic rat spinal cords. Male Wistar rats implanted with an intrathecal catheter received a single intrathecal PTX (1μg in 5μl saline) injection. Four days later, they were randomly assigned to receive either a single injection of saline, or ultra-low-dose naloxone (15ng in 5μl saline), followed by morphine (10μg in 5μl saline) injection 30 minutes later. The results showed that PTX injection induced thermal hyperalgesia and significant increase of global histone methylation in the spinal cords. Intrathecal morphine alone did not affect the thermal hyperalgesia and global histone methylation. In contrast, intrathecal administration of ultra-low-dose naloxone plus morphine significantly attenuated the PTX-induced thermal hyperalgesia and down-regulated the global histone methylation. The results suggest that ultra-low-dose naloxone might be clinical valuable for neuropathic pain management via regulating global histone modification.
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists. 09/2012; 50(3):106-11.
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    ABSTRACT: Ultra-low dose naloxone has been shown to restore the antinociceptive effect of morphine in pertussis toxin (PTX)-treated rats by suppressing spinal microglia activation and inhibiting inflammatory cytokine expression. This study was further investigated the mechanism by which ultra-low dose naloxone promotes analgesia in pertussis toxin-treated rats. Male Wistar rats were implanted with an intrathecal (i.t.) catheter and injected either saline or PTX (1 μg). Four days later, rats randomly received either saline, or ultra-low dose naloxone, or recombinant rat interleukin-10 (rrIL-10) (1 μg) injection followed by saline or morphine (10 μg) 30 min later. In some experiments, mouse anti-rat IL-10 antibody (10 μg) was injected intrathecally into PTX injected rats daily on days 4, 5, 6, and 7. On day 7, ultra-low dose naloxone was given 1h after antibody injection with or without subsequent morphine injection. PTX injection induced notable thermal hyperalgesia and mechanical allodynia. Injection of ultra-low dose naloxone preserved the antinociceptive effect of morphine in PTX-treated rats and associated an increasing of IL-10 protein expression. Intrathecal injection rrIL-10 alone or in combination with morphine, not only reversed mechanical allodynia but also partially restored the antinociceptive effect of morphine; injection of anti-rat IL-10 antibody attenuated the effect of morphine plus ultra-low dose naloxone on mechanical allodynia and completely inhibited the antinociceptive effect of morphine. These results indicate that intrathecal ultra-low dose naloxone induces IL-10 expression in spinal neuron and microglia, which suppresses PTX-induced neuroinflammation and restores the antinociceptive effect of morphine.
    Life sciences 07/2012; 91(5-6):213-20. · 2.56 Impact Factor
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    ABSTRACT: In the present study, we examined the effects and mechanisms of the Chinese herb resveratrol on attenuation of morphine tolerance in rats. Male Wistar rats were implanted with 2 intrathecal catheters; one catheter was connected to a mini-osmotic pump, used for either morphine (15 μg/h) or saline (1 μL/h) infusion for 5 days. On day 5, resveratrol (7.5, 15, 30, or 60 μg), dimethyl sulfoxide (5 μL), or saline (5 μL) was injected via the other catheter immediately after the discontinued morphine infusion. Three hours later, intrathecal morphine (15 μg in 5 μL saline) was given. All rats received the nociceptive tail-flick test every 30 minutes for 120 minutes after the morphine challenge. Long-term morphine infusion induced antinociceptive tolerance and up-regulated N-methyl-d-aspartate receptor (NMDAR) subunit NR1 and NR2B expression in the synaptosome fraction of the tolerant spinal cord dorsal horn. Resveratrol pretreatment provided a significant antinociceptive effect of morphine in morphine-tolerant rats, and it was associated with reversal of the up-regulated NR1 and NR2B subunits in the synaptosome fraction of morphine-tolerant rat spinal cords. NR1/NR2B-specific antagonist ifenprodil treatment produced a similar effect as that of resveratrol. Furthermore, an increase of postsynaptic density-95/NR1/NR2B complex immunoprecipitation in morphine-tolerant rat spinal cord was also inhibited by resveratrol pretreatment. Moreover, chronic morphine infusion activated glial cells with an increase of proinflammatory cytokine tumor necrosis factor-α, interleukin-1β, and interleukin-6 mRNA expression in morphine-tolerant rat spinal cords and these effects were suppressed by resveratrol pretreatment before the morphine challenge. Resveratrol attenuates morphine tolerance by inhibiting neuroinflammation and down-regulating NMDAR NR1 and NR2B subunit expression. Resveratrol regulates the NMDAR expression, which might be involved in a loss of scaffolding postsynaptic density-95 protein.
    Anesthesia and analgesia 06/2012; 115(4):944-52. · 3.08 Impact Factor
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    ABSTRACT: The tricyclic antidepressant amitriptyline binds with high affinity to N-methyl-d-aspartate receptors (NMDARs) and inhibits NMDAR-mediated events. Activation of the postsynaptic density protein-95 (PSD-95)/NMDAR-mediated downstream signaling cascade, including neuronal nitric oxide synthase (nNOS) and protein kinase gamma (PKCγ), has been shown to be involved in morphine tolerance. The present study examined the potential effect of amitriptyline on chronic morphine infusion-induced spinal PSD-95/NMDAR/nNOS/PKCγ signaling in morphine tolerance. Male Wistar rats were implanted with an intrathecal catheter and received an intrathecal infusion of saline or amitriptyline (15 μg/h), morphine+saline (tolerance induction, 15 μg/h), or morphine+amitriptyline for 5 days. Co-administration of amitriptyline with morphine not only preserved the antinociceptive effect of morphine, but also attenuated astrocyte activation in the rat spinal cord dorsal horn. On day 5 after drug infusion, increased expression and phosphorylation of spinal membrane NMDAR NR1 subunit and expression of PSD-95 were observed following chronic morphine infusion and these effects were attenuated by amitriptyline co-infusion. Upregulation of NMDAR-induced intracellular nNOS expression was also inhibited by amitriptyline co-infusion in chronic morphine-infused rats. Furthermore, amitriptyline co-infusion significantly inhibited morphine-induced PKCγ expression in both the cytosol and membrane of spinal neurons. These findings suggest that the attenuation of morphine tolerance caused by amitriptyline is due to downregulation of NMDAR NR1 subunit expression in the synaptosomal membrane accompanied by decreased expression of the scaffolding protein PSD-95. The effects of amitriptyline in attenuating astrocyte activation and reversing tolerance to morphine may be due, at least in part, to inhibition of the PSD-95/NMDAR NR1/nNOS/PKCγ signaling cascade.
    Behavioural brain research 04/2012; 229(2):401-11. · 3.22 Impact Factor
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    Chih-Shung Wong, Chun-Chang Yeh, Shan-Chi Ko
    Pain Management - Current Issues and Opinions, 01/2012; , ISBN: 978-953-307-813-7
  • Chih-Shung Wong
    Journal of the Formosan Medical Association 10/2011; 110(10):666; author reply 667. · 1.00 Impact Factor
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    ABSTRACT: Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.
    Anesthesiology 09/2011; 115(6):1229-38. · 5.16 Impact Factor
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    ABSTRACT: In this study, we examined the effects of ultra-low dose naloxone on the antinociceptive effect of morphine and on spinal cord dorsal horn glutamate transporter expression in rats with neuropathic pain. Neuropathic pain was induced in male Wistar rats by partial transection of the left sciatic nerve and an intrathecal catheter was implanted for drug administration; in some rats, an intrathecal microdialysis probe for cerebrospinal fluid (CSF) dialysate collection was also implanted. Nociception was assessed using the plantar test, a Hargreaves radiant heat apparatus, and by the von Frey test, using a dynamic plantar anesthesiometer. Glutamate transporter protein expression in the left spinal cord dorsal horn was examined by Western blotting and immunohistochemistry. Levels of the excitatory amino acids (EAAs) glutamate and aspartate in the CSF dialysate were measured using high-performance liquid chromatography. Reduced astrocyte expression of glutamate transporters (GLT-1 and GLAST levels were 55% and 53%, respectively, of that in sham-operated rats) in laminae I and II of the spinal cord dorsal horn ipsilateral to the partial sciatic nerve transection (PST), and hyperalgesia and allodynia in the PST hindlimb were observed. High-dose naloxone (15 μg) attenuated the antihyperalgesia and antiallodynia effects of the morphine (10 μg). In contrast, ultra-low dose (15 ng) naloxone enhanced the antinociceptive effect of morphine (10 μg), with an increase in the paw withdrawal threshold to thermal stimulus (from 19% to 35%) and to tactile stimulus (from 33% to 55%) compared with morphine treatment alone, and this was associated with restoration of GLAST and GLT-1 expression to control levels (102% and 114%, respectively) in the astrocytes of laminae I and II in the spinal cord dorsal horn ipsilateral to the PST hindlimb and a decrease in EAA levels in the CSF dialysate (glutamate: 10.0 μM; aspartate: 1.1 μM). Ultra-low dose naloxone enhanced the antinociceptive effect of morphine in PST rats, possibly by restoration of GLAST and GLT-1 expression in astrocytes, which inhibited the accumulation of EAAs in the synapses, resulting in a neuroprotective effect.
    Anesthesia and analgesia 08/2011; 113(6):1490-500. · 3.08 Impact Factor
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    ABSTRACT: Local anesthetic-induced neurotoxicity is one of the potential causes of postspinal anesthesia neurologic injury. Many experimental and clinical studies have demonstrated that lidocaine is more neurotoxic than bupivacaine. The mechanisms of local anesthetic-induced neurotoxicity remain unclear. Glutamate is an excitatory amino acid and widely exists in the central nervous system. Overstimulation of the glutamate receptors may produce neuronal toxic effect. In this study, we used in vivo microdialysis to examine the glutamate release in cerebrospinal fluid (CSF) after intrathecal lidocaine and bupivacaine injection. Male Wistar rats were used. Administration of lidocaine (5 groups: normal saline, 2.5%, 5%, 10%, and 10% + MK-801 intrathecally injected) and bupivacaine (4 groups: normal saline, 0.25%, 0.5%, and 1% intrathecally injected) was performed in both microdialysis and postinjection neurologic sequelae studies. After intrathecal injection of the studied agents, the CSF dialysates were collected in 10-minute intervals for 2 hours. Cerebrospinal fluid glutamate concentrations were measured by high-performance liquid chromatography. In addition, tail-flick latencies were examined daily before and after microdialysis for 4 days. Intrathecal lidocaine concentration-dependently elevated glutamate release in CSF. Pretreatment with MK-801 significantly inhibited the glutamate release induced by 10% lidocaine. Intrathecal bupivacaine has no influence on glutamate release in CSF. The tail-flick latencies were significantly prolonged for 4 days after intrathecal lidocaine injection, and these effects were in a concentration-dependent manner. Pretreatment with MK-801 significantly reversed the 10% lidocaine-induced prolonged tail-flick latencies. There was no difference of the tail-flick latencies among the bupivacaine-treated groups. Intrathecal lidocaine caused a concentration-dependent increase of the CSF glutamate release and postinjection neurologic impairment; these effects can be reversed by MK-801. However, intrathecal bupivacaine shows no influence. We suggest that glutamate may be involved in the pathogenesis of lidocaine-induced spinal neurotoxicity.
    Regional anesthesia and pain medicine 08/2011; 36(5):452-6. · 4.16 Impact Factor
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    ABSTRACT: Long-term exposure to morphine leads to analgesic tolerance. In addition to an opioid receptor conformational change, enhancing the glutamatergic signal transmission is also involved in morphine tolerance. Tumor necrosis factor-α has been demonstrated to correlate with neuronal plasticity via activation of glutamatergic transmission. We examined the effect of etanercept, a tumor necrosis factor-α inhibitor on morphine tolerance in rats. Male Wistar rats were implanted with 2 intrathecal (IT) catheters, and 1 IT catheter was connected to a mini-osmotic pump, used for either morphine infusion (15 μg/h) or saline (1 μL/h) infusion for 5 days. On day 5, either etanercept (50 μg) or saline (10 μL) was injected after discontinued morphine infusion. Three hours later, acute morphine (15 μg/10 μL, IT) treatment was given and all rats received a nociceptive tail-flick test. The results showed that acute etanercept (50 μg) treatment caused a significant antinociceptive effect of morphine in morphine-tolerant rats. Western blotting indicated that etanercept attenuated the downregulation of membrane glutamate transporters GLT-1 and GLAST in morphine-tolerant rats. Etanercept also inhibited the upregulation of surface AMPA-receptor and N-methyl-d-aspartate-receptor subunits, including GluR1/GluR2 and NR1/NR2A. These results demonstrate that etanercept partially restores the antinociceptive effect of morphine in morphine tolerance after a morphine challenge. Etanercept has potential for use in the clinical management of pain, particularly in patients who require long-term opioid treatment, and the effectiveness of which can be hampered by tolerance.
    Anesthesia and analgesia 07/2011; 113(1):184-90. · 3.08 Impact Factor

Publication Stats

1k Citations
280.63 Total Impact Points

Institutions

  • 2013
    • National Taipei University of Nursing Sciences
      T’ai-pei, Taipei, Taiwan
  • 2010–2013
    • Cathay General Hospital
      T’ai-pei, Taipei, Taiwan
  • 2006–2013
    • Taichung Armed Forces General Hospital
      臺中市, Taiwan, Taiwan
    • Chang Gung Memorial Hospital
      T’ai-pei, Taipei, Taiwan
    • Duke University Medical Center
      • Department of Anesthesiology
      Durham, NC, United States
  • 1999–2013
    • Tri-Service General Hospital
      T’ai-pei, Taipei, Taiwan
    • Buddhist Tzu Chi General Hospital
      T’ai-pei, Taipei, Taiwan
  • 2005–2012
    • National Yang Ming University
      • Department of Anesthesiology
      T’ai-pei, Taipei, Taiwan
  • 2005–2011
    • Taoyuan Armed Forces General Hospital
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2002–2011
    • National Defense Medical Center
      • • Department of Anesthesiology
      • • Tri-Service General Hospital
      T’ai-pei, Taipei, Taiwan
  • 2009
    • Johns Hopkins University
      • Department of Anesthesiology and Critical Care Medicine
      Baltimore, Maryland, United States
  • 2007
    • Kaohsiung Armed Forces General Hospital
      Kao-hsiung-shih, Kaohsiung, Taiwan
    • Taipei Veterans General Hospital
      • Department of Anesthesiology
      Taipei, Taipei, Taiwan
  • 2006–2007
    • Shin Kong Wu Ho-Su Memorial Hospital
      T’ai-pei, Taipei, Taiwan
  • 2004–2005
    • National Defense University, Taiwan
      Taoyuan City, Taiwan, Taiwan
  • 2003
    • VGHKS Kaohsiung Veterans General Hospital
      Kao-hsiung-shih, Kaohsiung, Taiwan