Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states

Doo Sik Kim, Kang Wu Li, Amin Boroujerdi, Yanhui Peter Yu, Chun Yi Zhou, Ping Deng, John Park, Xia Zhang, Joshua Lee, Michael Corpe, Kelli Sharp, Oswald Steward, Cagla Eroglu, Ben Barres, Frank Zaucke, Zao C. Xu, Z. David Luo

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Neuropathic pain is a common cause of pain after nerve injury, but its molecular basis is poorly understood. In a post-gene chip microarray effort to identify new target genes contributing to neuropathic pain development, we report here the characterization of a novel neuropathic pain contributor, thrombospondin-4 (TSP4), using a neuropathic pain model of spinal nerve ligation injury. TSP4 is mainly expressed in astrocytes and significantly upregulated in the injury side of dorsal spinal cord that correlates with the development of neuropathic pain states. TSP4 blockade by intrathecal antibodies, antisense oligodeoxynucleotides, or inactivation of the TSP4 gene reverses or prevents behavioral hypersensitivities. Intrathecal injection of TSP4 protein into naive rats is sufficient to enhance the frequency of EPSCs in spinal dorsal horn neurons, suggesting an increased excitatory presynaptic input, and to cause similar behavioral hypersensitivities. Together, these findings support that injury-induced spinal TSP4 may contribute to spinal presynaptic hypersensitivity and neuropathic pain states. Development of TSP4 antagonists has the therapeutic potential for target-specific neuropathic pain management.

Original languageEnglish (US)
Pages (from-to)8977-8987
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number26
DOIs
StatePublished - Jun 27 2012

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states'. Together they form a unique fingerprint.

  • Cite this

    Kim, D. S., Li, K. W., Boroujerdi, A., Yu, Y. P., Zhou, C. Y., Deng, P., Park, J., Zhang, X., Lee, J., Corpe, M., Sharp, K., Steward, O., Eroglu, C., Barres, B., Zaucke, F., Xu, Z. C., & David Luo, Z. (2012). Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states. Journal of Neuroscience, 32(26), 8977-8987. https://doi.org/10.1523/JNEUROSCI.6494-11.2012