Method for identifying compounds for treatment of pain

• US 7,718,382 B2
• Filed: 05/13/2005
• Issued: 05/18/2010
• Est. Priority Date: 05/14/2004
• Status: Expired due to Fees

• Current Assignee: Universite Laval
• Original Assignee: Universite Laval
• Inventors: Coull, Jeffrey A. M., De Koninck, Yves
• Primary Examiner(s): Saoud; Christine J
• Assistant Examiner(s): LOCKARD, JON MCCLELLAND
• Application Number:
  US11/596,087
• Publication Number:
  US 20080260718A1
• Time in Patent Office: 1,831 Days
• Field of Search: None
• US Class Current: 435/7.2
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/132 having two or more amino groups, e.g. spermidine, putrescine
• CPC Class Codes: A61K 31/265 of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: C07K 16/40 : against enzymes
• CPC Class Codes: C12N 15/1137 : against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/11 : Antisense
• CPC Class Codes: C12N 2310/14 : interfering N.A.
• CPC Class Codes: C12Q 1/44 : involving esterase
• CPC Class Codes: C12Y 301/04003 : Phospholipase C (3.1.4.3)
• CPC Class Codes: G01N 2333/916 : acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/5023 : on expression patterns

Abstract

The present invention provides methods of preventing and treating pain, by modulating, e.g. inhibiting, the activity, function and/or expression of a PLC_γ in a subject. The invention further relates to methods of identifying agents capable of modulating the activity and/or expression of a PLC_γ, or capable of modulating binding of a ligand or binding partner to a PLC_γ, and their use thereof for the prevention and/or treatment of pain. In a further aspect, the invention provides methods for the diagnosis and prognostication of pain by determining whether there is modulation of activity and/or expression of a PLC_γ relative to a corresponding control.

Claims

1. A method of identifying an agent for treatment of pain, comprising:

contacting the agent with a cell expressing a PLCγ

; and

determining whether there is inhibition of activity of said PLCγ

in the presence of the agent,

wherein inhibition of said activity is an indication that the agent may be used for the treatment of pain.

3. The method of claim 1, wherein the method comprises determining whether the agent inhibits the activity of said PLCγ

in a CNS cell or tissue.

4. The method of claim 3, wherein the CNS cell or tissue is a spinal cord cell or tissue.

5. The method of claim 3, wherein a pain signal originates in a PNS cell or sensory fiber transsynaptic to the CNS cell.

6. The method of claim 1, wherein the pain is neuropathic pain.

7. The method of claim 6, wherein the neuropathic pain is associated with a nerve or tract injury.

8. The method of claim 6, wherein the neuropathic pain is selected from the group consisting of somatic and visceral pain.

9. The method of claim 1, wherein the pain is selected from the group consisting of chronic inflammatory pain, pain associated with arthritis, fibromyalgia, back pain, cancer-associated pain, pain associated with digestive disease, pain associated with Crohn'"'"'s disease, pain associated with autoimmune disease, pain associated with endocrine disease, pain associated with diabetic neuropathy, phantom limb pain, spontaneous pain, chronic post-surgical pain, chronic temporomandibular pain, causalgia, post-herpetic neuralgia, AIDS-related pain, complex regional pain syndromes type I and II, trigeminal neuralgia, chronic back pain, pain associated with spinal cord injury and recurrent acute pain.

2. A method of identifying an agent for treatment of pain, comprising:

contacting the agent with a PLCγ

; and

determining whether there is inhibition of the activity of the PLCγ

in the presence of the agent,

wherein inhibition of said activity is an indication that the agent may be used for treatment of pain.

10. The method of claim 2, wherein the pain is neuropathic pain.

11. The method of claim 10, wherein the neuropathic pain is associated with a nerve or tract injury.

12. The method of claim 10, wherein the neuropathic pain is selected from the group consisting of somatic and visceral pain.

13. The method of claim 2, wherein the pain is selected from the group consisting of chronic inflammatory pain, pain associated with arthritis, fibromyalgia, back pain, cancer-associated pain, pain associated with digestive disease, pain associated with Crohn'"'"'s disease, pain associated with autoimmune disease, pain associated with endocrine disease, pain associated with diabetic neuropathy, phantom limb pain, spontaneous pain, chronic post-surgical pain, chronic temporomandibular pain, causalgia, post-herpetic neuralgia, AIDS-related pain, complex regional pain syndromes type I and II, trigeminal neuralgia, chronic back pain, pain associated with spinal cord injury and recurrent acute pain.