| HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS). | |
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MedLine Citation:
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PMID: 15288392 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It has become clear that spinal cord glia (microglia and astrocytes) importantly contribute to the creation of exaggerated pain responses. One model used to study this is peri-spinal (intrathecal, i.t.) administration of gp120, an envelope protein of HIV-1 known to activate glia. Previous studies demonstrated that i.t. gp120 produces pain facilitation via the release of glial proinflammatory cytokines. The present series of studies tested whether spinal nitric oxide (NO) contributes to i.t. gp120-induced mechanical allodynia and, if so, what effect NO has on spinal proinflammatory cytokines. gp120 stimulation of acutely isolated lumbar dorsal spinal cords released NO as well as proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta (IL1), interleukin-6 (IL6)), thus identifying NO as a candidate mediator of gp120-induced behavioral effects. Behaviorally, identical effects were observed when gp120-induced mechanical allodynia was challenged by i.t. pre-treatment with either a broad-spectrum nitric oxide synthase (NOS) inhibitor (L-NAME) or 7-NINA, a selective inhibitor of NOS type-I (nNOS). Both abolished gp120-induced mechanical allodynia. While the literature pre-dominantly documents that proinflammatory cytokines stimulate the production of NO rather than the reverse, here we show that gp120-induced NO increases proinflammatory cytokine mRNA levels (RT-PCR) and both protein expression and protein release (serial ELISA). Furthermore, gp120 increases mRNA for IL1 converting enzyme and matrix metalloproteinase-9, enzymes responsible for activation and release of proinflammatory cytokines. |
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Authors:
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Adelina Holguin; Kevin A O'Connor; Joseph Biedenkapp; Jay Campisi; Julie Wieseler-Frank; Erin D Milligan; Michael K Hansen; Leah Spataro; Elena Maksimova; Courtenay Bravmann; David Martin; Monika Fleshner; Steven F Maier; Linda R Watkins |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Pain Volume: 110 ISSN: 0304-3959 ISO Abbreviation: Pain Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-08-03 Completed Date: 2004-11-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7508686 Medline TA: Pain Country: Netherlands |
Other Details:
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Languages: eng Pagination: 517-30 Citation Subset: IM |
Affiliation:
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Department of Psychology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, CO 80309, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytokines / physiology* Enzyme Activation / drug effects, physiology HIV Envelope Protein gp120 / pharmacology* Inflammation Mediators / physiology* Male Nitric Oxide Synthase / metabolism*, physiology Nitric Oxide Synthase Type I Pain / enzymology*, virology Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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AI48555/AI/NIAID NIH HHS; AI51093/AI/NIAID NIH HHS; DA015642/DA/NIDA NIH HHS; MH00314/MH/NIMH NIH HHS; NS38020/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/HIV Envelope Protein gp120; 0/Inflammation Mediators; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nos1 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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