Methods for identifying analgesic agents
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. A method of predicting the analgesic effect on a human patient afflicted with chronic pain by an analgesic agent that selectively inhibits human SCN9A activity comprising determining in a cDNA or mRNA from said patient the presence or absence of a polymorphism that induces a mutated SCN9A polypeptide
wherein the absence of such polymorphism indicates that said agent is likely to produce an analgesic effect in said patient,
wherein the presence of said polymorphism indicates that said agent is less likely to produce an analgesic effect in said patient, and
wherein said mutated SCN9A polypeptide comprises the mutation Y328X, R830X, W1689X or a truncation of said polypeptide.
2. The method of claim 1 , wherein said chronic pain is neuropathic pain.
3. The method of claim 1 , wherein said polymorphism is identified by hybridizing an oligonucleotide complementary to a polynucleotide encoding said mutated SCN9A polypeptide.
4. The method of claim 3 , wherein said polynucleotide is a cDNA.
5. The method of claim 3 , wherein said polynucleotide is a mRNA.
6. The method of claim 1 , wherein the presence or absence of said polymorphism is determined by sequencing the gene for SCN9A.
7. The method of claim 1 , wherein said determination is made in a cDNA.
8. The method of claim 1 , wherein said determination is made in a mRNA.