Methods for treating neuropathological states and neurogenic inflammatory states and methods for identifying compounds useful therein

Abstract

The present invention provides methods for treating neuropathological states and neurogenic inflammatory states in a subject. The present invention also provides methods for identifying compounds that can be used to treat such states. Preferably, the compounds alter the distribution of NMDA glutamate receptor NR1 subunit in cells, and/or alter the production of TNFα by cells.

1 . A method for treating a neuropathological state in a subject, the method comprising: 
 administering to the subject an effective amount of a tyrosine kinase inhibitor.    
   
   
       2 . The method of  claim 1  wherein the tyrosine kinase inhibitor is selected from the group consisting of Genistein, Lavendustin A, K252a, and a combination thereof.  
   
   
       3 . The method of  claim 1  wherein the neuropathological state comprises a condition selected from the group consisting of persistent pain, arthritis, ulcerative colitis, inflammatory bowel disease, Crohn's disease, pancreatitis, asthma, stroke, brain injury, spinal cord injury, epileptogenesis, and viral invasion.  
   
   
       4 . (canceled)  
   
   
       5 . A method for treating a neuropathological state in a subject, the method comprising: 
 administering to the subject an effective amount of a compound that decreases the amount of NR1 subunit associated with a nucleus of a cell of the subject, wherein the cell comprises an NMDA glutamate receptor.    
   
   
       6 . The method of  claim 5  wherein the cell is a neuron.  
   
   
       7 . The method of  claim 5  wherein the neuron is a sensitized neuron.  
   
   
       8 . The method of  claim 5  wherein the neuron is prevented from being converted to a sensitized state.  
   
   
       9 . The method of  claim 5  wherein the neuropathological state comprises a condition selected from the group consisting of persistent pain, arthritis, ulcerative colitis, inflammatory bowel disease, Crohn's disease, pancreatitis, asthma, stroke, brain injury, spinal cord injury, epileptogenesis, and viral invasion.  
   
   
       10 . The method of  claim 5  where in the compound is a tyrosine kinase inhibitor.  
   
   
       11 . The method of  claim 10  wherein the tyrosine kinase inhibitor is selected from the group consisting of Genistein, Lavendustin A, K252a, and a combination thereof.  
   
   
       12 . (canceled)  
   
   
       13 . A method for treating a neuropathological state in a subject, the method comprising: 
 administering to the subject an effective amount of a compound that decreases the amount of Tumor Necrosis Factor α (TNFα) produced by a cell of the subject, wherein the cell comprises an NMDA glutamate receptor.    
   
   
       14 . The method of  claim 13  wherein the cell is a synovial cell.  
   
   
       15 . The method of  claim 13  wherein the neuropathological state comprises a condition selected from the group consisting of persistent pain, arthritis, ulcerative colitis, inflammatory bowel disease, Crohn's disease, pancreatitis, asthma, stroke, brain injury, spinal cord injury, and viral invasion.  
   
   
       16 . The method of  claim 13  wherein the compound is a tyrosine kinase inhibitor.  
   
   
       17 . The method of  claim 16  wherein the tyrosine kinase inhibitor is selected from the group consisting of Genistein, Lavendustin A, K252a, and a combination thereof.  
   
   
       18 - 24 . (canceled)  
   
   
       25 . A method for treating a neurogenic inflammatory state in a subject, the method comprising: 
 administering to the subject an effective amount of a compound that decreases the amount of TNFα produced by a cell of the subject, wherein the cell comprises an NMDA glutamate receptor.    
   
   
       26 . The method of  claim 25  wherein the compound is a tyrosine kinase inhibitor.  
   
   
       27 . The method of  claim 25  wherein the cell is a synovial cell.  
   
   
       28 - 31 . (canceled)