Document Detail


Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain.
MedLine Citation:
PMID:  11246166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The expression of interleukin-1beta and tumor necrosis factor has previously been shown to be up-regulated in the spinal cord of several rat mononeuropathy models. This present study was undertaken to determine whether blocking the action of central interleukin-1beta and tumor necrosis factor attenuates mechanical allodynia in a gender-specific manner in a rodent L5 spinal nerve transection model of neuropathic pain, and whether this inhibition occurs via down-regulation of the central cytokine cascade or blockade of glial activation. Interleukin-1 receptor antagonist or soluble tumor necrosis factor receptor was administered intrathecally via lumbar puncture to male Holtzman rats in a preventative pain strategy, in which therapy was initiated 1h prior to surgery. Administration of soluble tumor necrosis factor receptor attenuated mechanical allodynia, while interleukin-1 receptor antagonist alone was unable to decrease allodynia. Interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor, administered to both male and female rats in a preventative pain strategy, significantly reduced mechanical allodynia in a dose-dependent manner (P<0.01). The magnitude of attenuation in allodynia was similar in both males and females. Immunohistochemistry on L5 spinal cord revealed similar astrocytic and microglial activation regardless of treatment. At days 3 and 7 post-transection, animals receiving daily interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibited significantly less interleukin-6, but not interleukin-1beta, in the L5 spinal cord compared to vehicle-treated animals. In an existing pain paradigm, in which treatment was initiated on day 7 post-transection, interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor attenuated mechanical allodynia (P<0.05) in male rats. These findings further support a role for central interleukin-1beta and tumor necrosis factor in the development and maintenance of neuropathic pain through induction of a proinflammatory cytokine cascade.
Authors:
S Sweitzer; D Martin; J A DeLeo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroscience     Volume:  103     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2001  
Date Detail:
Created Date:  2001-03-14     Completed Date:  2001-06-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  529-39     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Hinman Box 7650, Dartmouth College, Hanover, NH 03755, USA. sarah.sweitzer@dartmouth.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Drug Therapy, Combination
Female
Immunoglobulin G / pharmacology*
Injections, Spinal
Interleukin 1 Receptor Antagonist Protein
Interleukin-1 / metabolism
Interleukin-6 / metabolism
Male
Neuralgia / drug therapy*,  immunology,  metabolism*
Neuroglia / immunology,  metabolism
Neurons / immunology,  metabolism
Rats
Rats, Sprague-Dawley
Receptors, Tumor Necrosis Factor
Sex Factors
Sialoglycoproteins / pharmacology*
Spinal Cord / cytology,  metabolism,  physiology
Spinal Nerves / physiopathology,  surgery
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
DA11276/DA/NIDA NIH HHS; F31 DA05969/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Immunoglobulin G; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; 0/Interleukin-6; 0/Receptors, Tumor Necrosis Factor; 0/Sialoglycoproteins; 0/Tumor Necrosis Factor-alpha; 185243-69-0/TNFR-Fc fusion protein

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


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