Document Detail


Prolonged nerve blockade delays the onset of neuropathic pain.
MedLine Citation:
PMID:  23045676     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain. Pharmacological blockade of that activity has been shown to mitigate the onset of associated molecular events in the nervous system. However, results in preventing onset of pain behaviors by providing prolonged nerve blockade have been mixed. Furthermore, the experimental techniques used to date to provide that blockade were limited in clinical potential in that they would require surgical implantation. To address these issues, we have used liposomes (SDLs) containing saxitoxin (STX), a site 1 sodium channel blocker, and the glucocorticoid agonist dexamethasone to provide nerve blocks lasting ~1 wk from a single injection. This formulation is easily injected percutaneously. Animals undergoing spared nerve injury (SNI) developed mechanical allodynia in 1 wk; nerve blockade with a single dose of SDLs (duration of block 6.9 ± 1.2 d) delayed the onset of allodynia by 2 d. Treatment with three sequential SDL injections resulting in a nerve block duration of 18.1 ± 3.4 d delayed the onset of allodynia by 1 mo. This very prolonged blockade decreased activation of astrocytes in the lumbar dorsal horn of the spinal cord due to SNI. Changes in expression of injury-related genes due to SNI in the dorsal root ganglia were not affected by SDLs. These findings suggest that formulations of this kind, which could be easy to apply clinically, can mitigate the development of neuropathic pain.
Authors:
Sahadev A Shankarappa; Jonathan H Tsui; Kristine N Kim; Gally Reznor; Jenny C Dohlman; Robert Langer; Daniel S Kohane
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17555-60     Citation Subset:  IM    
Affiliation:
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dexamethasone / administration & dosage
Liposomes
Nerve Block*
Neuralgia / prevention & control*
Rats
Saxitoxin / administration & dosage
Grant Support
ID/Acronym/Agency:
GM073626/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 35523-89-8/Saxitoxin; 50-02-2/Dexamethasone
Comments/Corrections
Erratum In:
Proc Natl Acad Sci U S A. 2013 May 7;110(19):7958

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


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