Biomarkers for Painful Intervertebral Discs and Methods of Use Thereof

Abstract

The present disclosure provides methods of diagnosing painful intervertebral discs. The present disclosure also provides methods of treating a painful intervertebral disc.

What is claimed is: 
     
         1 . A method of identifying a painful intervertebral disc, the method comprising assaying for an expression level of a gene product of at least one pain indicator gene selected from COL2A, COL9A3, AGC1, DCN, MMP3, MMP13, TIMP1, TIMP3, CD44, HIF1, IL8, IL1R, PLA2, TSG6, MMP9, Col1A1, Col3, BMP7, TNF-α, IL1β, PGE2, HIF1A, and ADAMTS5,
 wherein a decreased expression level of a gene product selected from COL2A, COL9A3, AGC1, DCN, MMP3, MMP13, TIMP1, TIMP3, CD44, HIF1, IL8, IL1R, PLA2, TSG6, MMP9, Col1A1, and Col3 in an intervertebral disc tissue, compared to a normal control value, indicates that the intervertebral disc is painful, and wherein an increased expression level of a gene product selected from BMP7, TNF-α, IL1β, PGE2, HIF1A, and ADAMTS5 in an intervertebral disc tissue, compared to a normal control value, indicates that the intervertebral disc is painful. 
 
     
     
         2 . The method of  claim 1 , wherein the intervertebral disc tissue is annulus fibrosus. 
     
     
         3 . The method of  claim 1 , wherein the intervertebral disc tissue is nucleus pulposus. 
     
     
         4 . The method of  claim 1 , wherein the gene product is a nucleic acid. 
     
     
         5 . The method of  claim 1 , wherein the gene product is a polypeptide. 
     
     
         6 . The method of  claim 5 , wherein the method comprises contacting the intervertebral disc tissue with an antibody specific for the polypeptide. 
     
     
         7 . The method of  claim 6 , wherein the antibody is detectably labeled. 
     
     
         8 . The method of  claim 7 , wherein binding of the detectably labeled antibody to the polypeptide is detected using an imaging method selected from magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. 
     
     
         9 . The method of  claim 1 , wherein the pain indicator gene product is a TSG6 gene product. 
     
     
         10 . The method of  claim 1 , further comprising administering a therapy for treatment of the painful intervertebral disc. 
     
     
         11 . The method of  claim 10 , wherein the therapy comprises surgery. 
     
     
         12 . The method of  claim 10 , wherein the therapy comprises administration of an agent. 
     
     
         13 . The method of  claim 1 , further comprising generating a report comprising information and/or a statement regarding the presence of a painful intervertebral disc in the individual. 
     
     
         14 . The method of  claim 13 , wherein the report is provided in an electronic medium. 
     
     
         15 . The method of  claim 13 , wherein the report is provided in a tangible medium. 
     
     
         16 . A method of treating intervertebral disc pain, the method comprising administering to an individual having intervertebral disc pain an effective amount of a tumor necrosis factor-alpha-induced protein 6 (TSG6) polypeptide, a polynucleotide comprising a nucleotide sequence encoding a TSG6 polypeptide, or a small molecule agent that increases the level of a TSG6 polypeptide in a cell. 
     
     
         17 . The method of  claim 16 , wherein said administering is local administration. 
     
     
         18 . The method of  claim 17 , wherein said administering is via bolus injection. 
     
     
         19 . The method of  claim 17 , wherein said administering is carried out using a device that provides for sustained release. 
     
     
         20 . The method of  claim 19 , wherein the device is a depot. 
     
     
         21 . The method of  claim 19 , wherein the device is a pump. 
     
     
         22 . The method of  claim 16 , wherein the TSG6 polypeptide comprises an amino acid sequence having at least about 75% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:1. 
     
     
         23 . The method of  claim 16 , wherein the agent comprises 2-methoxyestradiol.