Document Detail


Propofol produces immobility via action in the ventral horn of the spinal cord by a GABAergic mechanism.
MedLine Citation:
PMID:  19372332     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We investigated the actions of propofol and isoflurane on nociceptive responses of neurons in the spinal cord.
METHODS: We determined nociceptive responses of lumbar neurons in the dorsal horn (<1200 microm) and ventral horn (>1200 microm) of decerebrate rats before and during propofol (1 effective dose, ED(50)) or isoflurane (1 minimum alveolar concentration) anesthesia. During recording of ventral horn neurons, we administered picrotoxin by infusion to determine whether isoflurane and propofol differed in their effects at the gamma aminobutyric acid (GABA) Type A receptors. We also determined whether decerebration altered propofol requirements to produce immobility.
RESULTS: Decerebration did not affect propofol requirements. The ED(50) for propofol was 497 +/- 58 microg x kg(-1) x min(-1) in intact rats and 420 +/- 65 microg x kg(-1) x min(-1) in decerebrated rats (P > 0.05), with corresponding propofol blood concentrations of 8.1 +/- 1.1 microg/mL and 7.3 +/- 1.1 microg/mL, respectively (P > 0.05). Propofol did not significantly depress dorsal horn neurons, but isoflurane depressed the responses to 56% of control (P < 0.05). Propofol depressed ventral horn neurons to 47% of control, whereas isoflurane depressed ventral horn neurons to 20% of control. Picrotoxin significantly reversed the depressant effect of propofol on ventral horn neuronal responses (79% of control, not significantly different from control). Pic- rotoxin, however, had no effect on isoflurane's depression of ventral horn neuronal responses (26% of control).
CONCLUSIONS: Propofol acts in the spinal cord to produce immobility. This depressive effect occurs in the ventral horn and is mediated mainly by GABA(A) receptors. Isoflurane also depresses neurons in the ventral horn; however, isoflurane actions at the GABA(A) receptor are either weak or overridden by other effects in the ventral horn.
Authors:
Gudrun Kungys; Jongbun Kim; Steven L Jinks; Richard J Atherley; Joseph F Antognini
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  108     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-17     Completed Date:  2009-04-30     Revised Date:  2011-08-09    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1531-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology and Pain Medicine, University of California, Davis, California 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials
Anesthetics, Inhalation / administration & dosage
Anesthetics, Intravenous / administration & dosage*
Animals
Anterior Horn Cells / drug effects*,  metabolism
Decerebrate State
GABA Antagonists / administration & dosage
Immobilization*
Isoflurane / administration & dosage
Male
Movement / drug effects*
Pain Threshold / drug effects
Picrotoxin / administration & dosage
Posterior Horn Cells / drug effects,  metabolism
Propofol / administration & dosage*
Rats
Rats, Sprague-Dawley
Receptors, GABA-A / drug effects,  metabolism
gamma-Aminobutyric Acid / metabolism*
Grant Support
ID/Acronym/Agency:
GM47818/GM/NIGMS NIH HHS; GM61283/GM/NIGMS NIH HHS; GM78167/GM/NIGMS NIH HHS; P01 GM047818-12/GM/NIGMS NIH HHS; P01 GM047818-150006/GM/NIGMS NIH HHS; R01 GM061283-04/GM/NIGMS NIH HHS; R01 GM061283-07/GM/NIGMS NIH HHS; R01 GM078167-03/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Anesthetics, Intravenous; 0/GABA Antagonists; 0/Receptors, GABA-A; 124-87-8/Picrotoxin; 2078-54-8/Propofol; 26675-46-7/Isoflurane; 56-12-2/gamma-Aminobutyric Acid
Comments/Corrections
Comment In:
Anesth Analg. 2010 Feb 1;110(2):638; author reply 638   [PMID:  20081142 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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