Cellular correlates of anxiety in CA1 hippocampal pyramidal cells of 5-HT1A receptor knockout mice

5-HT1A receptor knockout (1AKO) mice have a robust anxiety phenotype. Tissue-specific “rescue” strategies and electrophysiology have implicated a critical role for postsynaptic 5-HT1A receptors, particularly in the CA1 region of the hippocampus. In this study, we evaluated differences in membrane properties and synaptic activity in CA1 hippocampal pyramidal cells between 1AKOs and wild-type (WT) controls to better understand the cellular correlates of anxiety in this mouse model. Whole-cell patch-clamp recordings were conducted in CA1 pyramidal cells in hippocampal brain slices from 1AKOs and WTs that had previously been screened for anxiety with the elevated-plus maze. Spontaneous miniature inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) and stimulus-evoked eIPSCs and eEPSCs were recorded in addition to the effect of the benzodiazepine agonist diazepam or the inverse agonist FG 7142 on ?-aminobutyric acid (GABA)ergic eIPSCs. Evoked EPSC amplitude was greater in 1AKOs than WTs. When subjects were pooled across genotypes, anxiety measures correlated with eEPSC amplitude, indicating enhanced postsynaptic glutamate synaptic activity under conditions of synaptic activation in anxious subjects. While GABA synaptic activity and sensitivity to diazepam were not affected by genotype or correlated with anxiety, sensitivity to the anxiogenic FG 7142 was smaller in anxious subjects. These data indicate enhanced postsynaptic glutamate receptor sensitivity and decreased GABAergic inhibition by a benzodiazepine inverse agonist in CA1 hippocampal neurons of anxious mice are produced by deletion of the 5-HT1A receptor. These data provide new information about interactions between 5-HT, GABA, and glutamate systems during the expression of chronic anxiety. Keywords  Serotonin - 5-HT1A receptor - Hippocampus - Anxiety - Elevated-plus maze - Electrophysiology

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Causes and Consequences of Inadequate Management of Acute Pain

Causes and Consequences of Inadequate Management of Acute Pain - Sinatra - 2010 - Pain Medicine - Wiley Online LibrarySkip to Main Content

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PUBLICATIONSBROWSE BY SUBJECTRESOURCESABOUT US LOGIN Enter e-mail address Enter password REMEMBER ME NOT REGISTERED ?FORGOTTEN PASSWORD ?INSTITUTIONAL LOGIN > JOURNAL TOOLS Get New Content Alerts Get RSS feed Save to My Profile Get Sample Copy JOURNAL MENU Journal Home FIND ISSUES Current IssueAll IssuesVirtual Issues FIND ARTICLES Early View GET ACCESS Subscribe / Renew FOR CONTRIBUTORS Author GuidelinesSubmit an Article ABOUT THIS JOURNAL Society InformationNewsOverviewEditorial BoardPermissionsAdvertiseContact SPECIAL FEATURES Professional OpportunitiesPainPoints Blog Causes and Consequences of Inadequate Management of Acute PainRaymond Sinatra MD, PhDArticle first published online: 28 OCT 2010

DOI: 10.1111/j.1526-4637.2010.00983.x

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Issue

Pain MedicineEarly View (Articles online in advance of print)

Additional Information

How to CiteSinatra, R. , Causes and Consequences of Inadequate Management of Acute Pain. Pain Medicine, no. doi: 10.1111/j.1526-4637.2010.00983.x

Author Information

Department of Anesthesiology, Yale School of Medicine, Yale?New Haven Hospital, New Haven, Connecticut, USA

*Correspondence: Raymond Sinatra, MD, PhD, Department of Anesthesiology, Yale School of Medicine, 20 York Street, Yale?New Haven Hospital, Tompkins Building, 3rd Floor, New Haven, Connecticut, USA. Tel: 203?785?2802; Fax: 203?785?6664; E?mail: rss9@email.med.yale.edu.

Publication HistoryArticle first published online: 28 OCT 2010 SEARCH Search Scope All contentPublication titlesIn this journalIn this issue Search String Advanced >Saved Searches > SEARCH BY CITATION Volume: Issue: Page: ARTICLE TOOLSGet PDF (342K)Save to My ProfileE-mail Link to this ArticleExport Citation for this ArticleRequest Permissions AbstractArticleReferencesCited By View Full Article (HTML) Get PDF (342K) Keywords:Acute Pain;Analgesia;Chronic Pain;OpioidAbstract

Context.? Intense acute pain afflicts millions of patients each year. Despite the recently increased focus on the importance of pain control, management of acute pain has remained suboptimal.

Objective.? The objective of this study was to identify through a review of recent literature the barriers to effective treatment of acute pain and the potential consequences of inadequate pain management.

Design.? A comprehensive literature review was conducted to identify articles relevant to the management of acute pain. Information regarding the underlying causes of inadequate pain management, as well as the sequelae associated with undermanaged pain was extracted and summarized.

Results.? Studies indicate that treatment of acute pain remains suboptimal due to attitudes and educational barriers on the part of both physicians and patients, as well as the intrinsic limitations of available therapies. Inadequate management of acute pain negatively impacts numerous aspects of patient health, and may increase the risk of developing chronic pain. Although opioids are the preferred treatment for most moderate to severe acute pain, their side effects can impede their use, and thus, their clinical effectiveness. Analgesic regimens with an improved efficacy/tolerability balance have the potential to improve acute pain management, and thus reduce the incidence of chronic pain. Studies examining the use of multiple analgesics with different mechanisms of action suggest that multimodal therapies may offer an improved efficacy/tolerability balance over single agent regimens.

Conclusions.? There exists a significant need for effective, well?tolerated analgesic therapies to limit the negative consequences of undermanaged acute pain. The use of multimodal therapy has demonstrated increasing promise and is supported by current practice guidelines.

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Copyright ? 1999-2010 John Wiley & Sons, Inc. All Rights Reserved.

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Preoperative Statin Use Reduces Mortality in Coronary Bypass Patients

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Esophageal stethoscope: an old tool with a new role, detection of residual flow during video-assisted thoracoscopic patent ductus arteriosus closure

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Cardiac intervention using high‐intensity focused ultrasound: creation of interatrial communication in beating heart of an anesthetized rabbit

Cardiac intervention using high?intensity focused ultrasound: creation of interatrial communication in beating heart of an anesthetized rabbit - Fujisaki - 2010 - Ultrasound in Obstetrics and Gynecology - Wiley Online LibrarySkip to Main Content

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Cardiac intervention using high?intensity focused ultrasound: creation of interatrial communication in beating heart of an anesthetized rabbitM. Fujisaki1,*, T. Chiba3, S. Enosawa4, T. Dohi2, S. Takamoto1Article first published online: 27 OCT 2010

DOI: 10.1002/uog.8830

Copyright ? 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Issue

Ultrasound in Obstetrics and GynecologyVolume 36, Issue 5, pages 607–612, November 2010

Additional Information

How to CiteFujisaki, M., Chiba, T., Enosawa, S., Dohi, T. and Takamoto, S. (2010), Cardiac intervention using high?intensity focused ultrasound: creation of interatrial communication in beating heart of an anesthetized rabbit. Ultrasound in Obstetrics and Gynecology, 36: 607–612. doi: 10.1002/uog.8830

Author Information1

Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

2

Department of Mechano?informatics, Graduate School of Information Science and Technology, University of Tokyo, Tokyo, Japan

3

Department of Strategic Medicine, National Center for Child Health and Development, Tokyo, Japan

4

Department of Regenerative Medicine Systems Biomedicine Unit, National Research Institute for Child Health and Development, Tokyo, Japan

Email: M. Fujisaki (masafujicardio@yahoo.co.jp)

*Correspondence: M. Fujisaki, Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, 7?3?1 Hongo Bunkyo?Ku Tokyo, Tokyo 1138655, Japan

Publication HistoryIssue published online: 27 OCT 2010Article first published online: 27 OCT 2010Accepted manuscript online: 14 SEP 2010 09:54AM ESTManuscript Accepted: 16 DEC 2009 SEARCH Search Scope All contentPublication titlesIn this journalIn this issue Search String Advanced >Saved Searches > SEARCH BY CITATION Volume: Issue: Page: ARTICLE TOOLSGet PDF (400K)Save to My ProfileE-mail Link to this ArticleExport Citation for this ArticleRequest Permissions AbstractArticleReferencesCited By View Full Article (HTML) Get PDF (400K) Keywords:balloon atrioseptostomy;BAS;cardiac intervention;computer?assisted;HIFU;high?intensity focused ultrasound;highly restrictive atrial septumAbstractObjective

Current fetal cardiac intervention for restrictive atrial septum is invasive and technically demanding. We investigated the feasibility of computer?assisted high?intensity focused ultrasound (HIFU) for cardiac intervention on the atrial septum of a beating heart.

Methods

To create an interatrial communication in the beating heart of nine anesthetized rabbits, the heart was exposed surgically and placed under a water?filled tank, in contact with the tank's membranous base. A HIFU transducer (3.3 MHz) coupled with a diagnostic ultrasound probe (10.0 MHz) was placed in the tank over the beating heart. The focus of the HIFU transducer was set so that it could create a hole in the target area on the atrial septum during the early diastolic phase. HIFU delivery was controlled based on ultrasound images captured with real?time image?recognition software. We attempted to create interatrial communication using HIFU and assessed the cardiac tissue specimen pathologically.

Results

In eight of nine rabbits, small holes in the atrial septum were successfully created. Serious complications occurred in two animals: a fatal atrioventricular block in one and a cardiac tamponade in the other.

Conclusion

HIFU combined with a computer?assisted imaging system might be useful to create interatrial communication in beating hearts. This procedure may be helpful for making current fetal cardiac intervention less invasive. Copyright ? 2010 ISUOG. Published by John Wiley & Sons, Ltd.

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Copyright ? 1999-2010 John Wiley & Sons, Inc. All Rights Reserved.

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