Dependence of monocyte chemoattractant protein 1 induced hyperalgesia on the isolectin B4-binding protein versican
- PMID: 19167466
- PMCID: PMC2684808
- DOI: 10.1016/j.neuroscience.2008.12.049
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.
Figures




Similar articles
-
IB4-saporin attenuates acute and eliminates chronic muscle pain in the rat.Exp Neurol. 2012 Feb;233(2):859-65. doi: 10.1016/j.expneurol.2011.12.019. Epub 2011 Dec 27. Exp Neurol. 2012. PMID: 22206923 Free PMC article.
-
Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat.Pain. 2014 Jun;155(6):1161-1167. doi: 10.1016/j.pain.2014.03.004. Epub 2014 Mar 15. Pain. 2014. PMID: 24637038 Free PMC article.
-
GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versican.Eur J Neurosci. 2008 Jul;28(1):12-9. doi: 10.1111/j.1460-9568.2008.06308.x. Epub 2008 Jun 28. Eur J Neurosci. 2008. PMID: 18616564 Free PMC article.
-
Hyperalgesic priming is restricted to isolectin B4-positive nociceptors.Neuroscience. 2010 Aug 11;169(1):431-5. doi: 10.1016/j.neuroscience.2010.04.082. Epub 2010 May 10. Neuroscience. 2010. PMID: 20457222 Free PMC article.
-
Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy.J Pain. 2008 May;9(5):463-72. doi: 10.1016/j.jpain.2008.01.335. Epub 2008 Mar 24. J Pain. 2008. PMID: 18359667
Cited by
-
IB4-saporin attenuates acute and eliminates chronic muscle pain in the rat.Exp Neurol. 2012 Feb;233(2):859-65. doi: 10.1016/j.expneurol.2011.12.019. Epub 2011 Dec 27. Exp Neurol. 2012. PMID: 22206923 Free PMC article.
-
Versican-A Critical Extracellular Matrix Regulator of Immunity and Inflammation.Front Immunol. 2020 Mar 24;11:512. doi: 10.3389/fimmu.2020.00512. eCollection 2020. Front Immunol. 2020. PMID: 32265939 Free PMC article. Review.
-
Extracellular matrix proteoglycan plays a pivotal role in sensitization by low pH of mechanosensitive currents in nociceptive sensory neurones.J Physiol. 2012 Jul 1;590(13):2995-3007. doi: 10.1113/jphysiol.2012.229153. Epub 2012 May 8. J Physiol. 2012. PMID: 22570376 Free PMC article.
-
The role(s) of cytokines/chemokines in urinary bladder inflammation and dysfunction.Biomed Res Int. 2014;2014:120525. doi: 10.1155/2014/120525. Epub 2014 Mar 12. Biomed Res Int. 2014. PMID: 24738044 Free PMC article. Review.
-
Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat.Pain. 2014 Jun;155(6):1161-1167. doi: 10.1016/j.pain.2014.03.004. Epub 2014 Mar 15. Pain. 2014. PMID: 24637038 Free PMC article.
References
-
- Alessandri-Haber N, Yeh JJ, Boyd AE, Parada CA, Chen X, Reichling DB, Levine JD. Hypotonicity induces TRPV4-mediated nociception in rat. Neuron. 2003;39:497–511. - PubMed
-
- Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999;68:729–777. - PubMed
-
- Bhangoo S, Ren D, Miller RJ, Henry KJ, Lineswala J, Hamdouchi C, Li B, Monahan PE, Chan DM, Ripsch MS, White FA. Delayed functional expression of neuronal chemokine receptors following focal nerve demyelination in the rat: a mechanism for the development of chronic sensitization of peripheral nociceptors. Molecular pain. 2007;3:38. - PMC - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous