期刊
NEUROSCIENCE
卷 159, 期 2, 页码 780-786出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.12.049
关键词
IB4; MCP-1; versican; sensory neurons; pain; inflammation
资金
- NINDS NIH HHS [P01 NS053709, P01 NS053709-02, R01 NS053880-04, R01 NS053880] Funding Source: Medline
The type 1 chemokine monocyte chemoattractant protein (MCP-1) has been implicated in the generation of inflammatory and neuropathic pain, but the underlying mechanism remains poorly understood. Here we show that mechanical hyperalgesia induced by intradermal injection of MCP-1 in the rat is blocked by the intrathecal administration of isolectin B4 (IB4)-saporin, a selective neurotoxin for IB4(+)/Ret(+)-nociceptors. MCP-1-induced hyperalgesia is also attenuated by intrathecal antisense oligodeoxynucleotides targeting mRNA for versican, a molecule that binds MCP-1 and that also renders the Ret-expressing nociceptors IB4-positive (+). Finally, peripheral administration of ADAMTS-4 or chondroitinase ABC, two enzymes that disrupt versican integrity by the degradation of the versican core-protein or its chondroitin sulfate glycosaminoglycan side chains, respectively, also attenuated MCPA hyperalgesia at the site of nociceptive testing. We suggest that versican's glycosaminoglycan side chains present MCP-1 to a CCR2 expressing cell type in the skin that, in turn, selectively activates IB4(+)/Ret(+) nociceptors, thereby contributing to enhanced mechanical sensitivity under inflammatory conditions. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
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