RGD Reference Report - Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states. - Rat Genome Database

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Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states.

Authors: Kim, DS  Li, KW  Boroujerdi, A  Peter Yu, Y  Zhou, CY  Deng, P  Park, J  Zhang, X  Lee, J  Corpe, M  Sharp, K  Steward, O  Eroglu, C  Barres, B  Zaucke, F  Xu, ZC  Luo, ZD 
Citation: Kim DS, etal., J Neurosci. 2012 Jun 27;32(26):8977-87. doi: 10.1523/JNEUROSCI.6494-11.2012.
RGD ID: 8553360
Pubmed: PMID:22745497   (View Abstract at PubMed)
PMCID: PMC3408211   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.6494-11.2012   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Thbs4Ratbehavioral response to pain involved_inIMP PMID:22745497UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Thbs4  (thrombospondin 4)

Additional Information