Dependence of monocyte chemoattractant protein 1 induced hyperalgesia on the isolectin B4-binding protein versican.

Abstract

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 MCP-1 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.

• Authors: O Bogen, O A Dina, R W Gear, J D Levine
• Journal: Neuroscience (Neuroscience) Vol. 159 Issue 2 Pg. 780-6 (Mar 17 2009) ISSN: 0306-4522 [Print] United States
• PMID: 19167466 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• IB4-saporin conjugate
• Lectins
• Neurotoxins
• Oligoribonucleotides, Antisense
• Ribosome Inactivating Proteins, Type 1
• Versicans
• Saporins
• ADAM Proteins
• Procollagen N-Endopeptidase
• ADAMTS4 Protein
• Chondroitin ABC Lyase

Topics

• ADAM Proteins (pharmacology)
• ADAMTS4 Protein
• Analysis of Variance
• Animals
• Chemokine CCL2
• Chondroitin ABC Lyase (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Hyperalgesia (chemically induced, drug therapy, metabolism)
• Lectins (therapeutic use)
• Male
• Neurotoxins (therapeutic use)
• Oligoribonucleotides, Antisense (therapeutic use)
• Pain Measurement (methods)
• Pain Threshold (drug effects)
• Procollagen N-Endopeptidase (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Ribosome Inactivating Proteins, Type 1 (therapeutic use)
• Saporins
• Time Factors
• Versicans (genetics, metabolism)