Claims
- 1. A method for treating pain in a subject in need thereof, comprising administering to the subject a therapeutically effective dose of a composition that decreases the current mediated by an HCN pacemaker channel in a sensory cell of the subject.
- 2. The method of claim 1 wherein the composition is delivered in combination with an analgesic.
- 4. The method of claim 1 wherein said pain is an inflammatory pain.
- 5. The method of claim 1, wherein said composition decreases the expression of an HCN protein subunit in a sensory cell of the subject.
- 6. The method of claim 1, wherein said composition decreases open probability of an HCN pacemaker channel in a sensory cell of the subject.
- 7. The method of claim 1, wherein said composition decreases the conductance of an HCN pacemaker channel to ions in a sensory cell of the subject.
- 8. The method of claim 1, wherein said composition is an inhibitor of an HCN1 or HCN3 channel.
- 9. The method of claim 1 wherein the pain is selected from the group consisting of carpal tunnel syndrome pain, back pain, neck pain, sciatica, intercostal neuralgia, opioid resistant pain, headache, cluster headache, migraine, trigeminal neuralgia, arthritis, osteoarthritis, and cancer-related pain.
- 10. The method of claim 1, wherein said composition is selected from ZD7288, ZM-227189, Zatebradine, DK-AH268, alinidine, and ivabradine.
- 11. The method of claim 1 wherein said other analgesic is selected from morphine or other opiate receptor agonists; nalbuphine or other mixed opioid agonist/antagonists; tramadol; baclofen; clonidine or other alpha-2 adrenoreceptor agonists; amitriptyline or other tricyclic antidepressants; gabapentin or pregabalin, carbamazepine, phenytoin, lamotrigine, or other anticonvulsants; and/or lidocaine, tocainide, or other local anesthetics/antiarrhythmics.
- 12. A method for treating pain in a subject in need thereof, comprising administering to the subject a therapeutically effective dose of a composition that decreases the expression of an HCN subunit in a sensory cell of the subject.
- 13. The method of claim 12 wherein the composition comprises an antisense nucleic acid or siRNA molecule specific for an HCN gene and wherein the antisense nucleic acid or siRNA molecule specifically suppresses HCN gene expression.
- 14. The method of claim 13 wherein said antisense nucleic acid or siRNA molecule specifically suppresses HCN1 or HCN3 gene expression.
- 15. An antibody that selectively binds to the carboxy-terminus of a HCN protein.
- 16. The antibody of claim 15 wherein the antibody selectively binds to the carboxy-terminus of a HCN1 or HCN3 protein.
- 17. A method of identifying a compound useful for treating pain, comprising the steps of:
(a) contacting a test compound with an HCN pacemaker protein; and (b) determining the ability of the to decrease a current mediated by an HCN pacemaker channel.
- 18. The method of claim 17 further comprising the step of testing the compound in at least one animal model for pain.
- 19. The method of claim 17, wherein the protein is an HCN1 or HCN3 pacemaker subunit.
- 20. The method of claim 17 wherein said HCN pacemaker protein is substantially purified.
- 21. The method of claim 17 wherein said HCN pacemaker protein is associated with a membrane.
- 22. The method of claim 17 wherein said HCN pacemaker protein is expressed from a host cell.
- 23. A method of identifying a compound useful for treating pain, comprising the steps of:
(a) contacting a test compound with a regulatory sequence for an HCN pacemaker gene or a cellular component that binds to the regulatory sequence for an HCN pacemaker gene; and (b) determining whether the test compound decreases the expression of a gene controlled by said regulatory sequence.
- 24. The method of claim 23 further comprising the step of testing the compound to at least one animal model for pain.
- 25. The method of claim 23 wherein the regulatory sequence is a regulatory sequence for an HCN1 or HCN3 gene.
- 26. The method of claim 23 wherein the gene controlled by the HCN regulatory sequence is a reporter gene.
- 27. The method of claim 23 wherein the gene controlled by the HCN regulatory sequence is an HCN gene.
- 28. The method of claim 23 wherein the regulatory sequence and the controlled gene thereof are inside a host cell.
- 29. A method of identifying a compound useful for treating pain, comprising the steps of:
(a) combining a test compound, a measurably labeled ligand for an HCN pacemaker protein, and an HCN pacemaker protein; and (b) measuring binding of the compound to the HCN pacemaker protein by a reduction in the amount of labeled ligand binding to the HCN pacemaker protein.
- 30. The method of claim 29 additionally comprising the step of testing the compound in at least one animal model for pain.
- 31. The method of claim 29 wherein said HCN pacemaker protein is substantially purified.
- 32. The method of claim 29 wherein said HCN pacemaker protein is associated with a membrane.
- 33. The method of claim 29 wherein said HCN pacemaker protein is expressed in a host cell.
- 34. The method of claim 29 wherein said protein is an HCN1 or HCN3 pacemaker protein.
- 35. A method for treating pain in an animal comprising the step of administering to the animal a composition including one or more inhibitors of an HCN pacemaker protein.
- 36. A method for treating inflammatory pain comprising administering to an animal a composition comprising one or more inhibitors of an HCN pacemaker protein.
FIELD OF THE INVENTION
[0001] This Patent application claims priority from U.S. Provisional Patent Application No. 60/297,108 filed Jun. 8, 2001 entitled “DRG 1H and HCN Association with Neuropathic Pain”, from U.S. Provisional Patent Application No. 60/347,945 filed Nov. 7, 2001 and entitled “Markedly Increased 1H and Regulation of HCN accompany Neuropathic Pain in the Rat”, and from U.S. Provisional Patent Application No. 60/373,012 filed Apr. 16, 2002 entitled “Treating Pain By Targeting Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channels”, the contents of which are hereby incorporated herein in their entirety.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60297108 |
Jun 2001 |
US |
|
60347945 |
Nov 2001 |
US |
|
60373012 |
Apr 2002 |
US |