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 utilizing the SCN9A gene and expression products thereof for the screening and identification of therapeutic agents, including small organic compounds, which are selective for SCN9A, and are useful in the treatment of pain and other disorders. The invention also relates to methods of using these compounds to treat or otherwise ameliorate such disorders.

1 - 38 . (canceled) 
     
     
         39 . An antisense nucleic acid molecule, comprising a nucleotide sequence that hydridizes to a polynucleotide containing the nucleotide sequence of SEQ ID NO: 1, 3, 5, 15, 17, or 19. 
     
     
         40 . The antisense nucleic acid molecule of  claim 39 , wherein said antisense nucleic acid molecule is a fragment of the nucleotide sequence complementary to SEQ ID NO: 1, 3, 5, 15, 17, or 19. 
     
     
         41 . The antisense nucleic acid molecule of  claim 39 , wherein said antisense nucleic acid is a DNA. 
     
     
         42 . The antisense nucleic acid molecule of  claim 39 , wherein said antisense nucleic acid is an RNA. 
     
     
         43 . The antisense nucleic acid molecule of  claim 39 , wherein said polynucleotide encodes the amino acid sequence of SEQ ID NO: 2, 4, 6, 16, 18 or 20. 
     
     
         44 . A therapeutic composition, comprising a therapeutically effective amount of an anti-sense nucleic acid molecule of  claim 39  in a pharmaceutically acceptable carrier. 
     
     
         45 . An antisense nucleic acid molecule, comprising a nucleotide sequence that hydridizes to a polynucleotide that encodes an SCN9A polypeptide. 
     
     
         46 . A method for treating a mammal afflicted with a condition related to sodium channel activity, comprising administering to said mammal an effective amount of an agent that selectively decreases SCN9A-mediated ion flux activity in said mammal. 
     
     
         47 . The method of  claim 46 , wherein said agent decreases the amount of SCN9A-mediated ion flux activity in said mammal. 
     
     
         48 . The method of  claim 46 , wherein said ion is sodium ion. 
     
     
         49 . The method of  claim 46 , wherein said mammal is a human patient. 
     
     
         50 . The method of  claim 46 , wherein said agent selectively decreases the expression of a gene encoding SCN9A. 
     
     
         51 . The method of  claim 50 , wherein said gene comprises the polynucleotide sequence of SEQ. ID NO. 1, 3, 5, 15, 17, or 19. 
     
     
         52 . The method of  claim 50 , wherein said gene encodes the amino acid sequence of SEQ. ID NO. 2, 4, 6, 16, 18 or 20. 
     
     
         53 . The method of  claim 46 , wherein said condition is chronic pain. 
     
     
         54 . The method of  claim 53 , wherein said chronic pain is neuropathic pain. 
     
     
         55 . The method of  claim 46 , wherein said condition is stroke. 
     
     
         56 . The method of  claim 46 , wherein said condition is epilepsy. 
     
     
         57 . The method of  claim 46 , wherein said agent is an analgesic agent. 
     
     
         58 . The method of  claim 46 , wherein said agent is an antisense nucleic acid. 
     
     
         59 . The method of  claim 58 , wherein said antisense nucleic acid hybridizes to a polynucleotide comprising the nucleotide sequence of SEQ. ID NO. 1, 3, 5, 15, 17, or 19. 
     
     
         60 . The method of  claim 59 , wherein said nucleotide sequence is SEQ. ID NO. 1. 
     
     
         61 . The method of  claim 59 , wherein said antisense nucleic acid is a fragment of the nucleotide sequence of SEQ. ID NO. 1, 3, 5, 15, 17, or 19. 
     
     
         62 . The method of  claim 61 , wherein said antisense nucleic acid is a fragment of the nucleotide sequence of SEQ. ID NO. 1. 
     
     
         63 . The method of  claim 58 , wherein said antisense nucleic acid hybridizes to a polynucleotide that encodes the amino acid sequence of SEQ. ID NO. 2, 4, 6, 16, 18 or 20. 
     
     
         64 . The method of  claim 63 , wherein said amino acid sequence is SEQ. ID NO. 2. 
     
     
         65 . The method of  claim 63 , wherein said antisense nucleic acid is a fragment of the polynucleotide that encodes the amino acid sequence of SEQ. ID NO. 2.