Source:http://linkedlifedata.com/resource/pubmed/id/10666520
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2-3
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pubmed:dateCreated |
2000-3-16
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pubmed:abstractText |
Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine IL-1beta, the transcription factor nuclear factor kappa B (NF-kappaB), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0. 3-85nmol), the NF-kappaB inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000pmol), the IL-1 receptor antagonist (IL-1ra) protein (0. 01-100ng), the caspase-1 inhibitor (YVAD) (0.1-300pmol), and the anti-inflammatory cytokine IL-10 (0.1-300ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-kappaB activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Dynorphins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0304-3959
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
84
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
159-67
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10666520-Animals,
pubmed-meshheading:10666520-Cytokines,
pubmed-meshheading:10666520-Dynorphins,
pubmed-meshheading:10666520-Hyperesthesia,
pubmed-meshheading:10666520-Interleukin-1,
pubmed-meshheading:10666520-Interleukin-10,
pubmed-meshheading:10666520-Male,
pubmed-meshheading:10666520-Mice,
pubmed-meshheading:10666520-Mice, Inbred ICR,
pubmed-meshheading:10666520-NF-kappa B,
pubmed-meshheading:10666520-Protein Biosynthesis
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pubmed:year |
2000
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pubmed:articleTitle |
Cytokine involvement in dynorphin-induced allodynia.
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pubmed:affiliation |
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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