Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin–treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway

Tsai, Ray Jui-Fang; Tai, Yueh-Hua; Tzeng, Jann Inn; Lin, Sheng-Hsiung; Shen, Ching-Hui; Yang, Ching‐Wen; Hsin, Shih-Tai; Wang, C.-B.; Wong, Chih Shung

doi:10.1016/j.neuroscience.2009.01.058

Cited by 28 publications

(34 citation statements)

References 52 publications

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“…Ultra-low dose naloxone suppresses microglia activation and induces IL-10 expression in spinal neuron and microglia in PTX-treated rats As in our previous study (Tsai et al, 2008(Tsai et al, , 2009b, weak immunostaining was observed in resting microglia (Fig. 1A).…”

Section: Resultssupporting

confidence: 79%

“…In our previous studies, intrathecal administration of ultra-low dose naloxone restored the antinociceptive effect of morphine, revered the coupling of μ-opioid receptors from Gs-protein to Gi-protein (Tsai et al, 2009a), suppressed microglia activation, inhibited the expression of IL-1β, IL-6, and phosphorylated p38 (P-p38) mitogen-activated protein kinase (MAPK) (Tsai et al, 2008(Tsai et al, , 2009b in PTX-treated rats. However, the anti-inflammation mechanisms of ultra-low dose naloxone remain unclear.…”

Section: Introductionmentioning

confidence: 94%

“…Spinal cord lysates, as described previously, were analyzed for TNF-α, IL-1β, IL-6, and IL-10 in a simultaneous multiplexed format using a microbead and flow-based protein detection system (Bio-Plex Suspension Array System, Bio-Rad Laboratories Inc., Hercules, CA, USA) (Tsai et al, 2009b;Lin et al, 2010). In this quantitative assay system, specific antibodies directed against each cytokine are conjugated to the surface of fluorescence-coded microbeads, each fluorescencecoded microbead type being conjugated to one specific capture antibody.…”

Section: Measurement Of Cytokine Proteinsmentioning

confidence: 99%

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Ultra-low dose naloxone restores the antinocicepitve effect of morphine in PTX-treated rats: Association of IL-10 upregulation in the spinal cord

et al. 2012

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Section: Resultssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 94%

Section: Measurement Of Cytokine Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Ultra-low dose naloxone restores the antinocicepitve effect of morphine in PTX-treated rats: Association of IL-10 upregulation in the spinal cord

et al. 2012

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“…We opted to use them instead of more traditional anti-inflammatory agents because naloxone in ultralow concentrations has been suggested to have anti-inflammatory properties (27) in addition to its powerful effect as a -opioid receptor antagonist. Also, ultralow dose naloxone is effective in restoration of the antinociceptive effect of morphine in rats and in addition increases anti-inflammatory cytokine IL-10 expression (26).…”

Section: Discussionmentioning

confidence: 97%

“…We hypothesized that the astrocytes are influenced by the inflammation inducer LPS and that it is possible to restore some aspects of the cells to a homeostatic state using exposure to a substance that may have anti-inflammatory properties. We aimed to test this using naloxone, particularly in very low concentrations (26,27). We further aimed to test ouabain in low and high concentrations and its effects of Na ϩ /K ϩ -ATPase activity (28) and evoked Ca 2ϩ transients in astrocytes (28 -30).…”

Section: Interleukin-1␤ (Il-1␤) Release Was Increased After 24 H In Lpsmentioning

confidence: 99%

Naloxone and Ouabain in Ultralow Concentrations Restore Na+/K+-ATPase and Cytoskeleton in Lipopolysaccharide-treated Astrocytes

Forshammar

Block

Lundborg

et al. 2011

Journal of Biological Chemistry

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Infection, tissue damage, or other conditions can lead to a neuroinflammatory state. Lipopolysaccharide (LPS) exposure can be used experimentally as a model to generate an inflammatory response both in vitro and in vivo. Endotoxin, or LPS, is a potent inflammatory activator (1) in astrocytes and microglia, with stimulation of Toll-like receptor 4 (TLR4) (2). The expression of TLR4 is up-regulated in astrocytes under neuroinflammatory conditions (3). Activation of TLR4 leads to activation of nuclear factor-B, a factor that regulates expression of genes involved in immune responses, including release of the proinflammatory cytokines tumor necrosis factor-␣ (TNF-␣) and interleukin-1␤ (IL-1␤) (2).Astrocytes in networks, positioned between the vasculature and synapses, monitor neuronal signaling, including rebuilding of synapses (4, 5). Astrocytes express almost the same repertoire of receptors and ion channels as neurons. They regulate synaptic transmission via a bidirectional communication with neurons, and they release gliotransmitters as well as factors, including cytokines, fatty acid metabolites, and free radicals (6 -8).The Ca 2ϩ signaling in astrocytes over long distances is analogous to, but much slower than, the propagation of action potentials in neurons (9). These astrocytic Ca 2ϩ waves (10, 11) can be evoked by transmitters released from neurons and glial cells, followed by activation of especially G protein-coupled receptors. Cytosolic Ca 2ϩ plays a key role as a second messenger, and the control of Ca 2ϩ signals is therefore critical. This involves coordination of Ca 2ϩ entry across the plasma membrane (PM), 2 Ca 2ϩ release from the endoplasmatic reticulum (ER), refilling of the ER stores, and extrusion across the PM (12). The Na ϩ -Ca 2ϩ exchanger, a Ca 2ϩ transporter that controls the intracellular Ca 2ϩ concentrations, is driven by the Na ϩ electrochemical gradient across the PM. This Na ϩ pump, Na ϩ /K ϩ -ATPase, indirectly modulates Ca 2ϩ signaling (13), and inflammatory stimuli influence Ca 2ϩ homeostasis in the astrocyte networks (5, 14 -16).The cytoskeleton seems to be important in this system for controlling of PM microdomains and the ER complex. The adaptor protein ankyrin B is associated with the Na ϩ pump and also with ER proteins, such as the inositol 1,4,5-trisphosphate (IP 3 ) receptor. The main cytoplasmic matrix of proteins, spectrin and actin, are attached to ankyrin B. An intact cytoskeleton is required for the propagation of astrocytic Ca 2ϩ waves (17)

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Ultra-low-dose naloxone enhances the antinociceptive effect of morphine in PTX-treated rats: Regulation on global histone methylation

Tsai

Shen

Feng

et al. 2012

Acta Anaesthesiologica Taiwanica

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show abstract

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin–treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway

Cited by 28 publications

References 52 publications

Ultra-low dose naloxone restores the antinocicepitve effect of morphine in PTX-treated rats: Association of IL-10 upregulation in the spinal cord

Ultra-low dose naloxone restores the antinocicepitve effect of morphine in PTX-treated rats: Association of IL-10 upregulation in the spinal cord

Naloxone and Ouabain in Ultralow Concentrations Restore Na+/K+-ATPase and Cytoskeleton in Lipopolysaccharide-treated Astrocytes

Ultra-low-dose naloxone enhances the antinociceptive effect of morphine in PTX-treated rats: Regulation on global histone methylation

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