阅读说明：本技术 神经周施用树脂毒素治疗适应不良性疼痛 (Treatment of maladaptive pain with perinervous resiniferatoxin administration ) 是由 亚历西斯·拿哈马 于 2019-12-20 设计创作，主要内容包括：本文公开了神经周施用树脂毒素(RTX)以治疗适应不良性疼痛的方法和用于此类方法中的组合物。(Disclosed herein are methods of perineurally administering Resiniferatoxin (RTX) to treat maladaptive pain and compositions for use in such methods.)

1. A method of treating maladaptive pain comprising perineurally administering a Resiniferatoxin (RTX) to a subject in need of treatment for maladaptive pain.

2. A composition comprising a Resiniferatoxin (RTX) for use in a method of treating maladaptive pain, the method comprising peripherically administering the RTX to a subject in need of treatment for maladaptive pain.

3. The method or composition for use according to claim 1 or 2, wherein the method comprises administering a dose of 0.1 μ g to 100 μ g of RTX.

4. The method or composition for use according to claim 3, wherein said dose of RTX is in the range of 0.1-1 μ g, 1-2 μ g, 2-5 μ g, 5-10 μ g, 10-20 μ g, 20-30 μ g, 30-40 μ g, 40-50 μ g, 50-60 μ g, 60-70 μ g, 70-80 μ g, 80-90 μ g, or 90-100 μ g.

5. The method or composition for use according to any of the preceding claims, wherein the RTX is administered perineurally to a single site, multiple sites, sciatic nerve, saphenous nerve, femoral nerve, radial nerve, ulnar nerve, median nerve, dermatomyocutaneous nerve, and/or volar nerve.

6. The method or composition for use according to any of the preceding claims, wherein the RTX is neuronally administered to multiple sites that collectively correspond to sensory input from one or more fingers, feet or hands, forelimbs, limbs and/or joints.

7. The method or composition for use according to any one of the preceding claims, wherein the subject is an amputee.

8. The method or composition for use according to any one of the preceding claims, wherein the neuro-weekly administration targets one or more nerve fibers downstream of the amputation site.

9. The method or composition for use according to any one of the preceding claims, wherein the subject suffers from phantom limb pain or stump pain.

10. The method or composition for use according to any one of claims 7 to 9, wherein the neuronally administered target is at least two, three, four or five nerve fibers downstream of the amputation site.

11. The method or composition for use according to any one of the preceding claims, wherein the subject has abnormal nerve growth at nerve endings.

12. The method or composition for use according to claim 11, wherein the neuro-weekly administration targets one or more nerve fibers downstream of a nerve having abnormal growth at a peripheral terminus.

13. The method or composition for use according to any one of the preceding claims, wherein the neuro-weekly administration targets one or more nerve fibers downstream of a neuroma.

14. The method or composition for use according to any one of the preceding claims, wherein the method comprises administering a pharmaceutical formulation comprising the RTX and a pharmaceutically acceptable carrier.

15. The method or composition for use according to claim 14, wherein the pharmaceutically acceptable carrier comprises water.

16. The method or composition for use according to claim 14 or 15, wherein the pharmaceutically acceptable carrier comprises polysorbate 80.

17. The method or composition for use according to any one of claims 14 to 16, wherein the pharmaceutically acceptable carrier comprises polyethylene glycol.

18. The method or composition for use according to any one of claims 14 to 17, wherein the pharmaceutically acceptable carrier comprises a sugar or sugar alcohol.

19. The method or composition for use according to claim 18, wherein the pharmaceutically acceptable carrier comprises mannitol.

20. The method or composition for use according to claim 18 or 19, wherein the pharmaceutically acceptable carrier comprises dextrose.

21. The method or composition for use according to any one of claims 14 to 20, wherein the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable buffer.

22. The method or composition for use according to claim 21, wherein the pharmaceutically acceptable carrier comprises a phosphate buffer.

23. The method or composition for use according to any one of claims 14 to 22, wherein the pH of the pharmaceutical formulation is in the range of 6 to 7.6.

24. The method or composition for use according to claim 23, wherein the pH of the pharmaceutical formulation is in the range of 6 to 6.4, 6.3 to 6.7, 6.4 to 6.8, 6.8 to 7.2, 7 to 7.4 or 7.2 to 7.6.

25. The method or composition for use according to claim 23, wherein the pH of the pharmaceutical formulation is 6.5 or 7.2.

26. The method or composition for use according to any one of claims 14 to 25, wherein the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable salt.

27. The method or composition for use according to claim 26, wherein the pharmaceutically acceptable salt is NaCl.

28. The method or composition for use according to any one of claims 14 to 27, wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.02-0.1 μ g/ml or 0.1 to 300 μ g/ml.

29. The method or composition for use according to claim 28, wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.02-0.1 μ g/ml, 0.1-1 μ g/ml, 1-5 μ g/ml, 5-10 μ g/ml, 10-20 μ g/ml, 20-50 μ g/ml, 50-100 μ g/ml, 100-150 μ g/ml, 150-200 μ g/ml, 200-250 μ g/ml or 250-300 μ g/ml.

30. The method or composition for use according to claim 28 or 29, wherein the concentration of RTX in the pharmaceutical formulation is in the range of 150 to 250 μ g/ml, or is about 200 μ g/ml.

31. The method or composition for use according to claim 28 or 29, wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.1-200 μ g/ml, optionally wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.1-50 μ g/ml.

32. The method or composition for use according to any one of the preceding claims, wherein the RTX is administered in an injection volume of 0.05-10ml, optionally wherein the injection volume is in the range of 0.05-0.2ml, 0.2-0.5ml, 0.5-1ml, 1-2ml, 2-5ml or 5-10 ml.

33. The method or composition for use according to any one of the preceding claims, wherein the subject is a mammal.

34. The method or composition for use according to claim 33, wherein the subject is a cat, dog, horse, pig, ruminant, bovine, ovine, caprine or domestic mammal.

35. The method or composition for use according to claim 33, wherein the subject is a human.

36. The method or composition for use of any one of the preceding claims, wherein the treatment reduces the local and central effects of maladaptive pain.

37. The method or composition for use of any one of the preceding claims, wherein the subject has one or more behavioral symptoms adapted for adverse pain prior to treatment, and the treatment reduces or eliminates the one or more behavioral symptoms.

Embodiment 2 is a composition comprising a Resiniferatoxin (RTX) for use in a method of treating maladaptive pain, the method comprising peripherically administering the RTX to a peripheral nerve of a subject in need of treatment for maladaptive pain.