Methods For Identifying Analgesic Agents

Abstract

The present invention relates to the discovery that mutations in SCN9A are causative of Congenital Indifference to Pain (CIP) in humans. The invention also relates to methods of using compounds small organic compounds to treat pain as well as to predict the effect of analgesic agents in patients, such as those possessing gain of function mutations.

What is claimed is: 
     
         1 . A method of treating pain in a patient having a gain of function nucleotide polymorphism in an SCN9A gene, comprising administering to said patient a sodium channel blocking agent that selectively inhibits SCN9A polypeptide. 
     
     
         2 . The method of  claim 1 , wherein said gain of function polymorphism results in an SCN9A polypeptide having a tryptophan at amino acid 1150. 
     
     
         3 . The method of  claim 1 , wherein said sodium channel blocking agent is compound A. 
     
     
         4 . The method of  claim 1 , wherein said SCN9A gene without said polymorphism has the nucleotide sequence of SEQ ID NO: 3. 
     
     
         5 . The method of  claim 1 , wherein said SCN9A polypeptide has the amino acid sequence of SEQ ID NO: 2. 
     
     
         6 . A method of predicting the analgesic effect of a sodium channel blocking agent that selectively inhibits SCN9A polypeptide in a mammal, comprising:
 (a) determining in said mammal the presence of a gain of function polymorphism in an SCN9A gene of said mammal,   (b) administering to said mammal an effective amount of Compound A, and   (c) determining a positive analgesic effect in said mammal due to said administering of step (b),   wherein said positive analgesic effect in step (c) indicates a positive analgesic effect by said sodium channel blocking agent.   
     
     
         7 . The method of  claim 6 , wherein said gain of function polymorphism results in an SCN9A polypeptide having a tryptophan at amino acid 1150. 
     
     
         8 . The method of  claim 6 , wherein said sodium channel blocking agent is an analog of compound A. 
     
     
         9 . The method of  claim 6 , wherein said SCN9A gene without said polymorphism has the nucleotide sequence of SEQ ID NO: 3. 
     
     
         10 . The method of  claim 6 , wherein said SCN9A polypeptide has the amino acid sequence of SEQ ID NO: 2. 
     
     
         11 . The method of  claim 6 , wherein said mammal is a human being.