Pain treatment using ERK2 inhibitors
This application describes methods and compositions for reducing, inhibiting and/or treating pain that involve use of ERK2 inhibitors.
1. A method for treating or inhibiting pain in an animal comprising administering to the animal specific inhibitor of extracellular signal-regulated kinase 2 (ERK2) to thereby treat or inhibit pain in the animal without reducing inflammation, wherein the inhibitor is a nucleic acid that can inhibit the expression of ERK2.
2. The method of claim 1 , wherein the animal is a human, domesticated animal, experimental animal or a zoo animal.
3. The method of claim 1 , wherein the inhibitor is administered locally.
4. The method of claim 1 , wherein the nucleic acid can hybridize to an mRNA encoding a ERK2 polypeptide with SEQ ID NO: 2.
5. The method of claim 1 , wherein the nucleic acid can hybridize to an ERK2 polynucleotide comprising SEQ ID NO:2 and/or SEQ ID NO:771.
6. The method of claim 1 , wherein the nucleic acid is a small interfering RNA.
7. The method of claim 1 , wherein the nucleic acid has a modified backbone or one or more non-natural internucleoside linkages.
8. The method of claim 1 , wherein the nucleic acid is a small interfering RNA comprising a DNA or RNA sequence with any of SEQ ID NO:3-162, 166-764, 765, 769, 770, 773, 774, 775, or a combination thereof; and/or a DNA or RNA that can specifically hybridize to any of SEQ ID NO:3-162, 166-764, 765, 769, 770, 773, 774, 775, or a combination thereof.
9. The method of claim 1 , wherein the nucleic acid is a small interfering RNA comprising a DNA or RNA sequence with any of SEQ ID NO: 765, 769, 770, 773, 774, 775, or a combination thereof; and/or a DNA or RNA that can specifically hybridize to any of SEQ ID NO: 765, 769, 770, 773, 774, 775, or a combination thereof.
10. The method of claim 1 , wherein the nucleic acid is a small interfering RNA comprising a DNA or RNA sequence corresponding to any one SEQ ID NO: 773, 774, 775, 779, 782, 785, or a combination thereof.
11. The method of claim 1 , wherein the nucleic acid is encoded within an expression cassette comprising a promoter and a polynucleotide segment comprising a DNA or RNA corresponding to any of SEQ ID NO: SEQ ID NO:3-162, 166-764, 765, 769, 770, 773-775, 779, 782, 785, or a combination thereof.
12. The method of claim 11 , wherein the segment comprises X-L-Y, wherein X is a sense sequence, L is a spacer linked to the 3′ end of the sense sequence, and Y is an antisense sequence linked to the 3′ end of the linker, and wherein the Y antisense sequence is complementary to the X sequence so that upon expression of the polynucleotide segment, a short hairpin RNA (shRNA) is generated.
13. The method of claim 11 , wherein the expression cassette is present in an expression vector.
14. The method of claim 11 , wherein the expression vector is within a neurotropic recombinant adeno-associated virus (rAAV).
15. The method of claim 1 , wherein administering the nucleic acid that can inhibit the expression of ERK2 does not significantly change ERK1 expression.
16. The method of claim 1 , wherein the pain is neuropathic pain.
17. The method of claim 1 , wherein the nucleic acid is expressed from a viral vector, which is a neurotropic recombinant adeno-associated virus vector.
18. A method for treating or inhibiting inflammatory pain in an animal comprising administering to the animal's central nervous system or spinal fluid a specific inhibitor of extracellular signal-regulated kinase 2 (ERK2) to thereby treat or inhibit pain in the animal without reducing inflammation, wherein the inhibitor is a nucleic acid that can inhibit the expression of ERK2.