Nitrous Oxide Produces Antinociceptive Response via α2Band/or α2CAdrenoceptor Subtypes in Mice 

1999 ◽  
Vol 90 (2) ◽  
pp. 470-476 ◽  
Author(s):  
Tian-Zhi Guo ◽  
Frances M. Davies ◽  
Wade S. Kingery ◽  
Andrew J. Patterson ◽  
Lee E. Limbird ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Transgenic Mice ◽  
Time Course ◽  
Antinociceptive Effect ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Tail Flick ◽  
Wild Type ◽  
Tail Flick Latency ◽  
In The Wild

Background Opiate receptors in the periaqueductal gray region and alpha2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2O). The availability of genetically altered mice facilitates the detection of the precise protein species involved in the transduction pathway. In this study, the authors establish the similarity between rats and mice in the antinociceptive action of N2O and investigate which alpha2 adrenoceptor subtypes mediate this response. Methods After obtaining institutional approval, antinociceptive dose-response and time-course to N2O was measured in wild-type and transgenic mice (D79N), with a nonfunctional alpha2A adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemically with yohimbine (nonselective alpha2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral alpha2-antagonist) and prazosin (alpha2B- and alpha2C-selective antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective alpha2 agonist, was tested in wild-type and transgenic mice. Results N2O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic mice. Antinociception from N2O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinociceptive response could be dose dependently antagonized by opiate receptor and selective alpha2B-/alpha2C-receptor antagonists but not by a central nervous system-impermeant alpha2 antagonist (L659,066). Whereas dexmedetomidine exhibited no antinociceptive response in the D79N mice, the robust antinociceptive response in the wild-type litter mates could not be blocked by a selective alpha2B-/alpha2C-receptor antagonist. Conclusion These data confirm that the antinociceptive response to an exogenous alpha2-agonist is mediated by an alpha2A adrenoceptor and that there appears to be a role for the alpha2B- or alpha2C-adrenoceptor subtypes, or both, in the analgesic response to N2O.

Antinociceptive Response to Nitrous Oxide Is Mediated by Supraspinal Opiate and Spinal α2Adrenergic Receptors in the Rat

1996 ◽  
Vol 85 (4) ◽  
pp. 846-852 ◽  
Author(s):  
Tian-Zhi Guo ◽  
Lawrence Poree ◽  
Wendy Golden ◽  
Joshua Stein ◽  
Masahiko Fujinaga ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Opiate Receptors ◽  
Opioid Analgesics ◽  
Opiate Receptor ◽  
Antagonistic Effect ◽  
Tail Flick ◽  
Endogenous Opiates ◽  
Tail Flick Latency ◽  
Latency Response ◽  
Enclosed Chamber

Background Despite nearly 150 years of clinical use, the mechanism(s) of action of nitrous oxide (N2O) remains in doubt. In some but not all studies the analgesic properties of N2O can be attenuated by opiate receptor antagonists. The purported mechanism for the opiate antagonistic effect relates to the finding that N2O increases supraspinal levels of endogenous opiates, although this finding has been disputed. Based on the observations that (1) N2O promotes the release of catecholamines, including the endogenous alpha 2 adrenergic agonist norepinephrine, and (2) that descending noradrenergic inhibitory pathways are activated by opioid analgesics, this study sought to determine whether alpha 2 adrenergic receptors are involved in the antinociceptive action of nitrous oxide. Methods Institutional approval was obtained for the study. Rats breathed 70% N2O and 30% O2 in an enclosed chamber. After a 30-min exposure, significant antinociception was indicated by an increase in the latency response to a noxious stimulus (tail-flick latency). The tail-flick latency was tested in rats exposed to 70% N2O after either systemic or regional (intrathecal or intracerebroventricular) injections with either competitive (atipamezole; yohimbine) or noncompetitive (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) alpha 2 adrenoceptor antagonists, or the opiate receptor antagonist naloxone. Results When administered systemically, both the opiate (naloxone) and alpha 2 adrenoceptor antagonists (atipamezole, yohimbine, and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) blocked the enhanced tail-flick latency response to N2O-Naloxone administered intracerebroventricularly, but not intrathecally, blocked the enhanced tail-flick latency response to N2O. Conversely, atipamezole administered intrathecally, but not intracerebroventricularly, blocked the enhanced tail-flick latency response to N2O. Conclusions These data suggest that both supraspinal opiate and spinal alpha 2 adrenoceptors play a mediating role in the antinociceptive response to N2O in rats. A possible mechanism may involve a descending inhibitory noradrenergic pathway that may be activated by opiate receptors in the periaqueductal gray region of the brain stem in the rat after exposure to N2O.

Low Concentrations of Halothane Increase Response to a Noxious Thermal Stimulus and Attenuate the Antinociceptive Effect of Intraventricular but Not Intrathecal Morphine

2001 ◽  
Vol 94 (2) ◽  
pp. 298-302 ◽  
Author(s):  
Kenneth Drasner
Keyword(s):  
Pain Perception ◽  
Intrathecal Morphine ◽  
Antinociceptive Effect ◽  
Maximum Effect ◽  
Tail Flick ◽  
Temperature Threshold ◽  
Thermal Stimulus ◽  
Descending Inhibition ◽  
Low Concentrations ◽  
Tail Flick Latency

Background Classically, the first plane of anesthesia is known as the stage of analgesia. Nonetheless, clinical evidence suggests that low doses of inhaled agents might enhance pain perception. The present experiments test the hypothesis that low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular morphine via disruption of descending inhibition. Methods In the first experiment, the temperature at which rats withdraw their tails from a heat source was measured in animals breathing various concentrations of halothane. In the second experiment, the effect of intraventricular or intrathecal morphine on tail-flick latency was assessed in rats breathing either oxygen or 0.23% halothane. Results Low concentrations of halothane decreased the temperature threshold for tail-flick with a maximum effect at 0.06% atmospheres. Halothane attenuated the antinociceptive potency of intraventricular morphine but enhanced the efficacy of intrathecal morphine. Conclusions Subanesthetic concentrations of halothane may enhance response to a noxious stimulus. The differential effect on intraventricular and intrathecal morphine suggests that this enhancement results from disruption of descending inhibition.

Dexmedetomidine Enhances Analgesic Action of Nitrous Oxide

2004 ◽  
Vol 100 (4) ◽  
pp. 894-904 ◽  
Author(s):  
Cecilia Dawson ◽  
Daqing Ma ◽  
Andre Chow ◽  
Mervyn Maze
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Neuronal Activity ◽  
Locus Ceruleus ◽  
Tail Flick ◽  
Receptor Subtypes ◽  
Dental Surgery ◽  
Analgesic Effects ◽  
Adrenoceptor Antagonist ◽  
Tail Flick Latency

Background Nitrous oxide and dexmedetomidine are thought to mediate analgesia (antinociception in a noncommunicative organism) via alpha 2B- and alpha 2A-adrenergic receptor subtypes within the spinal cord, respectively. Nitrous oxide and dexmedetomidine exert diametrically opposite effects on neuronal activity within the locus ceruleus, a pivotal site for modulation of analgesia. Because of these differences, the authors explored whether the two analgesics in combination would provide satisfactory analgesia. Methods The analgesic effects of nitrous oxide and dexmedetomidine given both intraperitoneally and intrathecally were evaluated using the tail-flick latency test in rats. For investigation of the interaction, rats were pretreated with dexmedetomidine, either intraperitoneally or intrathecally, immediately before nitrous oxide exposure such that peak antinociceptive effects of each drug coincided. For assessment of the effect on tolerance, dexmedetomidine was administered as tolerance to nitrous oxide developed. Expression of c-Fos was used to assess neuronal activity in the locus ceruleus. Results Nitrous oxide and dexmedetomidine increased tail-flick latency with an ED50 (mean +/- SEM) of 55.0 +/- 2.2% atm for nitrous oxide, 27.6 +/- 5.1 for microg/kg intraperitoneal dexmedetomidine, and 2.9 +/- 0.1 microg for intrathecal dexmedetomidine. Combinations of systemically administered dexmedetomidine and nitrous oxide produced an additive analgesic interaction; however, neuraxially administered dexmedetomidine interacted synergistically with nitrous oxide. Tolerance to nitrous oxide was reversed by coadministration of dexmedetomidine. Prazosin, the alpha 1-/alpha 2B-adrenoceptor antagonist, attenuated the analgesic effect of nitrous oxide and prevented dexmedetomidine-induced reversal of tolerance to nitrous oxide. Nitrous oxide-induced increase of neuronal activity in the locus ceruleus was reversed by dexmedetomidine. Conclusion The synergistic analgesic interaction between nitrous oxide and dexmedetomidine within the spinal cord is obscured by a supraspinal antagonism when dexmedetomidine is administered systemically in the pretolerant state. After tolerance to nitrous oxide develops, supraspinal functional antagonism no longer obtains exposing the synergistic action at the level of the spinal cord, which expresses itself as a reversal of the tolerant state. The authors speculate that the addition of dexmedetomidine to nitrous oxide is likely to provide enhanced and more durable analgesia in settings in which nitrous oxide is currently used alone (e.g., labor and dental surgery).

scholarly journals Effect of arsenite on swimming motility delays surface colonization in Herminiimonas arsenicoxydans

Microbiology ◽  
2010 ◽  
Vol 156 (8) ◽  
pp. 2336-2342 ◽  
Author(s):  
M. Marchal ◽  
R. Briandet ◽  
S. Koechler ◽  
B. Kammerer ◽  
P. N. Bertin
Keyword(s):  
Laser Scanning ◽  
Time Course ◽  
Wild Type Strain ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Wild Type ◽  
Arsenite Oxidase ◽  
Swimming Motility ◽  
In The Wild ◽  
Biofilm Development

Herminiimonas arsenicoxydans is a Gram-negative bacterium able to detoxify arsenic-contaminated environments by oxidizing arsenite [As(III)] to arsenate [As(V)] and by scavenging arsenic ions in an extracellular matrix. Its motility and colonization behaviour have been previously suggested to be influenced by arsenite. Using time-course confocal laser scanning microscopy, we investigated its biofilm development in the absence and presence of arsenite. Arsenite was shown to delay biofilm initiation in the wild-type strain; this was partly explained by its toxicity, which caused an increased growth lag time. However, this delayed adhesion step in the presence of arsenite was not observed in either a swimming motility defective fliL mutant or an arsenite oxidase defective aoxB mutant; both strains displayed the wild-type surface properties and growth capacities. We propose that during the biofilm formation process arsenite acts on swimming motility as a result of the arsenite oxidase activity, preventing the switch between planktonic and sessile lifestyles. Our study therefore highlights the existence, under arsenite exposure, of a competition between swimming motility, resulting from arsenite oxidation, and biofilm initiation.

Nitrous Oxide Lacks the Antinociceptive Effect on the Tail Flick Test in Newborn Rats

2000 ◽  
Vol 91 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Masahiko Fujinaga ◽  
Ryan Doone ◽  
M. Frances Davies ◽  
Mervyn Maze
Keyword(s):  
Nitrous Oxide ◽  
Antinociceptive Effect ◽  
Tail Flick ◽  
Newborn Rats ◽  
Tail Flick Test

scholarly journals Time course of neuropathological events in hyperhomocysteinemic amyloid depositing mice reveals early neuroinflammatory changes that precede amyloid changes and cerebrovascular events

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Erica M. Weekman ◽  
Tiffany L. Sudduth ◽  
Brittani R. Price ◽  
Abigail E. Woolums ◽  
Danielle Hawthorne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Time Course ◽  
Control Diet ◽  
Interleukin 1 ◽  
Amyloid Deposition ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Co Morbidity ◽  
In The Wild

Abstract Background Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind only Alzheimer’s disease (AD); however, VCID is commonly found as a co-morbidity with sporadic AD. We have previously established a mouse model of VCID by inducing hyperhomocysteinemia in both wild-type and amyloid depositing mice. While we have shown the time course of neuropathological events in the wild-type mice with hyperhomocysteinemia, the effect of amyloid deposition on this time course remains unknown; therefore, in this study, we determined the time course of neuropathological changes in our mouse model of hyperhomocysteinemia-induced VCID in amyloid depositing mice. Methods APP/PS1 mice were placed on either a diet deficient in folate and vitamins B6 and B12 and enriched in methionine to induce hyperhomocysteinemia or a control diet for 2, 6, 10, 14, or 18 weeks. Immunohistochemistry and gene expression analysis were used to determine neuroinflammatory changes. Microhemorrhages and amyloid deposition were analyzed using histology and, finally, behavior was assessed using the 2-day radial arm water maze. Results Neuroinflammation, specifically a pro-inflammatory phenotype, was the first pathological change to occur. Specifically, we see a significant increase in gene expression of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and interleukin 12a by 6 weeks. This was followed by cognitive deficits starting at 10 weeks. Finally, there is a significant increase in the number of microhemorrhages at 14 weeks on diet as well as redistribution of amyloid from the parenchyma to the vasculature. Conclusions The time course of these pathologies points to neuroinflammation as the initial, key player in homocysteine-induced VCID co-morbid with amyloid deposition and provides a possible therapeutic target and time points.

Altered cytokinin distribution in the shootless maize mutant ed*41

2001 ◽  
Vol 28 (4) ◽  
pp. 307 ◽  
Author(s):  
Adriana Chiappetta ◽  
Walter de Witte ◽  
Milvia L. Racchi ◽  
Maria B. Bitonti ◽  
Henri van Onckelen ◽  
...  
Keyword(s):  
Zea Mays ◽  
Apical Meristem ◽  
Time Course ◽  
Zea Mays L ◽  
Wild Type ◽  
Vascular Connection ◽  
Vascular Tissues ◽  
In The Wild ◽  
Specific Synthesis

The distribution of cytokinins is strongly altered in seedlings of the shootless ed*41 mutant of maize (Zea mays L.), compared with wild-type. Immunolocalisation of zeatin and analysis of cytokinin levels clearly indicate that these hormones are not present in the shoot apex zone of the mutant. Since an anomalous differentiation of vascular tissues has also been observed in the mutant, a major role of vascular connection in hormone translocation affecting development of the shoot apical meristem is proposed. Immunolocalisation of zeatin was confined to the root cap, cortex and vascular tissues of both mutant and wild-type seedlings suggesting a tissue-specific synthesis of this hormone in the root. A time-course of cytokinin distribution in the wild-type developing shoot provided evidence that the tunica and corpus zones become competent to respond to cytokinins in subsequent periods, very probably in conjunction with photomorphogenesis. On the contrary, this pathway is totally disrupted in the mutant. Taken together, the data point to a relationship between the ed*41 mutation, inadequate vascular connection and disrupted hormone translocation.

Antinociceptive effects of intrathecally administered human β-endorphin in the rat and cat

1978 ◽  
Vol 56 (5) ◽  
pp. 754-759 ◽  
Author(s):  
Tony L. Yaksh ◽  
James L. Henry
Keyword(s):  
Subarachnoid Space ◽  
Antinociceptive Effect ◽  
Intrathecal Injection ◽  
Opiate Receptor ◽  
Tail Flick ◽  
Dose Ratio ◽  
Response Curves ◽  
Indwelling Catheter ◽  
Spinal Subarachnoid Space

Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-plate and tail-flick response latencies following the injection of human β-endorphin into the lumbar spinal subarachnoid space through the indwelling catheter. β-Endorphin was approximately 25 times more potent than morphine on a molar basis. Matching morphine and β-endorphin doses such that approximately equal submaximal effects occurred, it was observed that the antinociception produced by β-endorphin lasted approximately three times longer than that produced by morphine. Experiments with intrathecal injection of β-endorphin into the spinal subarachnoid space of cats fitted with intrathecal catheters also revealed a potent antinociceptive effect which was completely antagonized by naloxone. In the rats, naloxone administered systemically in doses of 10–100 μg/kg produced a parallel shift in the dose–response curves of both nociceptive measures suggesting a competitive antagonism. Using a dose ratio analysis, an in vivo pA2 of 7.1 for naloxone was obtained. These data and those derived from previous work based on the pA2 suggest that the interaction of morphine, certain pentapeptides, and β-endorphin is the same with regard to the spinal opiate receptor population mediating behavioraily defined analgesia.

scholarly journals Transcriptional Control by A-Factor of Two Trypsin Genes in Streptomyces griseus

2005 ◽  
Vol 187 (1) ◽  
pp. 286-295 ◽  
Author(s):  
Jun-ya Kato ◽  
Won-Jae Chi ◽  
Yasuo Ohnishi ◽  
Soon-Kwang Hong ◽  
Sueharu Horinouchi
Keyword(s):  
Type Strain ◽  
Transcriptional Control ◽  
Time Course ◽  
Wild Type Strain ◽  
Streptomyces Griseus ◽  
Trypsin Activity ◽  
Wild Type ◽  
Regulatory Cascade ◽  
Transcriptional Start Point ◽  
In The Wild

ABSTRACT AdpA is the key transcriptional activator for a number of genes of various functions in the A-factor regulatory cascade in Streptomyces griseus, forming an AdpA regulon. Trypsin-like activity was detected at a late stage of growth in the wild-type strain but not in an A-factor-deficient mutant. Consistent with these observations, two trypsin genes, sprT and sprU, in S. griseus were found to be members of the AdpA regulon; AdpA activated the transcription of both genes by binding to the operators located at about −50 nucleotide positions with respect to the transcriptional start point. The transcription of sprT and sprU, induced by AdpA, was most active at the onset of sporulation. Most trypsin activity exerted by S. griseus was attributed to SprT, because trypsin activity in an sprT-disrupted mutant was greatly reduced but that in an sprU-disrupted mutant was only slightly reduced. This was consistent with the observation that the amount of the sprT mRNA was much greater than that of the sprU transcript. Disruption of both sprT and sprU (mutant ΔsprTU) reduced trypsin activity to almost zero, indicating that no trypsin genes other than these two were present in S. griseus. Even the double mutant ΔsprTU grew normally and developed aerial hyphae and spores over the same time course as the wild-type strain.

scholarly journals Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage

2006 ◽  
Vol 5 (10) ◽  
pp. 1688-1704 ◽  
Author(s):  
Iran Malavazi ◽  
Marcela Savoldi ◽  
Sônia Marli Zingaretti Di Mauro ◽  
Carlos Frederico Martins Menck ◽  
Steven D. Harris ◽  
...  
Keyword(s):  
Dna Damage ◽  
Aspergillus Nidulans ◽  
Mutant Strain ◽  
Deletion Mutant ◽  
Time Course ◽  
Excision Repair ◽  
Wild Type ◽  
Significant Difference ◽  
Mutant Strains ◽  
In The Wild

ABSTRACT We have used an Aspergillus nidulans macroarray carrying sequences of 2,787 genes from this fungus to monitor gene expression of both wild-type and uvsB ATR (the homologue of the ATR gene) deletion mutant strains in a time course exposure to camptothecin (CPT). The results revealed a total of 1,512 and 1,700 genes in the wild-type and uvsB ATR deletion mutant strains that displayed a statistically significant difference at at least one experimental time point. We characterized six genes that have increased mRNA expression in the presence of CPT in the wild-type strain relative to the uvsB ATR mutant strain: fhdA (encoding a forkhead-associated domain protein), tprA (encoding a hypothetical protein that contains a tetratrico peptide repeat), mshA (encoding a MutS homologue involved in mismatch repair), phbA (encoding a prohibitin homologue), uvsC RAD51 (the homologue of the RAD51 gene), and cshA (encoding a homologue of the excision repair protein ERCC-6 [Cockayne's syndrome protein]). The induced transcript levels of these genes in the presence of CPT require uvsB ATR. These genes were deleted, and surprisingly, only the ΔuvsC mutant strain was sensitive to CPT; however, the others displayed sensitivity to a range of DNA-damaging and oxidative stress agents. These results indicate that the selected genes when inactivated display very complex and heterogeneous sensitivity behavior during growth in the presence of agents that directly or indirectly cause DNA damage. Moreover, with the exception of UvsC, deletion of each of these genes partially suppressed the sensitivity of the ΔuvsB strain to menadione and paraquat. Our results provide the first insight into the overall complexity of the response to DNA damage in filamentous fungi and suggest that multiple pathways may act in parallel to mediate DNA repair.

Sign in / Sign up

Export Citation Format

Share Document