Urgency therapy with neuromodulation and C-afferent nerve desensitization

• US 9,289,607 B2
• Filed: 08/16/2011
• Issued: 03/22/2016
• Est. Priority Date: 08/18/2010
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Su, Xin, Molnar, Gregory F., Nelson, Dwight E.
• Primary Examiner(s): Stigell, Theodore
• Assistant Examiner(s): CAREY, MICHAEL JAMES
• Application Number:
  US13/817,486
• Publication Number:
  US 20140142549A1
• Time in Patent Office: 1,680 Days
• Field of Search: 607/41, 607/40, 607/143
• US Class Current: 1/1
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61M 2205/054 with electrotherapy
• CPC Class Codes: A61M 2210/1085 Bladder
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/36057 adapted for stimulating afferent nerves
• CPC Class Codes: A61N 1/36062 Spinal stimulation
• CPC Class Codes: A61N 1/36071 Pain
• CPC Class Codes: A61N 1/36171 Frequency
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 20/30 relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising

Abstract

Systems (10), devices (16), and methods may be used for treating bladder dysfunction, such as urgency and pelvic pain. In one example, a method includes administering a pharmacological agent to a patient (14) in a dosage sufficient to desensitize a C-afferent nerve fiber of the patient. Additionally, the method includes delivering stimulation to activate a nerve fiber proximate to the C-afferent nerve fiber via an electrode (19A, 19B, 21A, 21B, 29A-29D) electrically coupled to an implantable medical device (16). In some examples, the nerve fiber may be different than the C-afferent nerve fiber, the stimulation of the nerve fiber may elicit an inhibitory physiological response related to voiding in the patient, and/or the stimulation substantially may not activate the C-afferent nerve fiber after desensitization of the nerve fiber via the administration of the pharmacological agent.

Claims

1. A method comprising:

administering a pharmacological agent to a patient in a dosage sufficient to desensitize a C-afferent nerve fiber of the patient; and

delivering electrical stimulation to activate a nerve fiber proximate to the C-afferent nerve fiber via an electrode electrically coupled to an implantable medical device, wherein the nerve fiber is different than the C-afferent nerve fiber, wherein the stimulation of the nerve fiber elicits an inhibitory physiological response related to voiding in the patient, and wherein the stimulation substantially does not activate the C-afferent nerve fiber after desensitization of the nerve fiber via the administration of the pharmacological agent.

2. The method of claim 1, wherein the nerve fiber comprises at least one of an A-delta (Aδ

) nerve fiber or an A-beta (Aβ

) nerve fiber.

3. The method of claim 1, wherein the nerve fiber is an efferent nerve fiber.

4. The method of claim 1, wherein the nerve fiber forms a portion of at least one of a spinal nerve, a sacral nerve, a pelvic nerve, a pudendal nerve, dorsal genital nerve, a tibial nerve, an inferior rectal nerve, or a perineal nerve.

5. The method of claim 1, wherein the inhibitory physiological response comprises a reduction of a frequency of bladder contractions of the patient.

6. The method of claim 1, wherein delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device comprises delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device at a pulse frequency of less than about 60 Hz.

7. The method of claim 1, wherein delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device comprises delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device at a pulse frequency of between about 0.1 Hz and about 20 Hz.

8. The method of claim 1, wherein delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device comprises delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device at a stimulation intensity of between about one-half of a threshold stimulation intensity and about three times the threshold stimulation intensity.

9. The method of claim 1, wherein delivering stimulation to the nerve fiber proximate to the C-afferent nerve fiber via the electrode electrically coupled to the implantable medical device comprises:

delivering stimulation at a first stimulation intensity during a first time period, wherein the stimulation elicits a first inhibitory physiological response related to voiding in the patient during the first time period, and wherein the first time period is at least about 5 minutes;

delivering stimulation at a second stimulation intensity during a second time period immediately following the first time period, wherein the second stimulation intensity is less than the first stimulation intensity, wherein the stimulation elicits a second inhibitory physiological response related to voiding in the patient during the second time period, wherein the second inhibitory physiological response is greater than the first inhibitory physiological response, and wherein the second time period is at least about 5 minutes; and

delivering stimulation at the first stimulation intensity during a third time period, wherein the third time period immediately follows the second time period.

10. The method of claim 1, wherein administering the pharmacological agent to the patient comprises administering at least one of a sodium channel blocker, a calcium channel blocker, botulinum toxin, or capsaicin to the patient.

11. The method of claim 1, wherein administering the pharmacological agent to the patient comprises administering the pharmacological agent to the patient via intravesical injection in a bladder of the patient.

12. The method of claim 1, wherein administering the pharmacological agent to the patient comprises administering the pharmacological agent to the patient via a catheter fluidically coupled to an implantable drug delivery device.

13. A method comprising:

receiving via a control module of an implantable medical device an indication that a pharmacological agent has been administered in a dosage sufficient to desensitize a C-afferent nerve fiber to a patient in which the implantable medical device is implanted;

selecting via the control module an electrical stimulation therapy program based on the received indication; and

controlling via the control module a therapy delivery module to generate and deliver electrical stimulation therapy in accordance with the electrical stimulation therapy program to activate a nerve fiber proximate to the C-afferent nerve fiber, wherein the nerve fiber is different than the C-afferent nerve fiber, wherein the electrical stimulation therapy elicits an inhibitory physiological response related to voiding in the patient, and wherein the electrical stimulation therapy substantially does not activate the C-afferent nerve fiber after desensitization of the nerve fiber via the administration of the pharmacological agent.

14. The method of claim 13, wherein the nerve fiber comprises at least one of an A-delta (Aδ

) nerve fiber or an A-beta (Aβ

) nerve fiber.

15. The method of claim 13, wherein the nerve fiber comprises an efferent nerve fiber.

16. The method of claim 13, wherein the nerve fiber forms a portion of at least one of a spinal nerve, a sacral nerve, a pelvic nerve, a pudendal nerve, dorsal genital nerve, a tibial nerve, an inferior rectal nerve, or a perineal nerve.

17. The method of claim 13, wherein the inhibitory physiological response comprises a reduction of a frequency of bladder contractions of the patient.

18. The method of claim 13, wherein the electrical stimulation therapy program defines a pulse frequency of the electrical stimulation therapy, and wherein the pulse frequency is less than about 60 Hz.

19. The method of claim 13, wherein the electrical stimulation therapy program defines a stimulation intensity, and wherein the stimulation intensity is between about one-half of a threshold stimulation intensity and about three times the threshold stimulation intensity.

20. The method of claim 13, wherein controlling via the control module the therapy delivery module to generate and deliver electrical stimulation therapy in accordance with the electrical stimulation therapy program comprises controlling via the control module the therapy delivery module to generate and deliver stimulation at a first stimulation intensity for a first time period, to deliver stimulation at a second stimulation intensity for a second time period immediately following the first time period, and to deliver stimulation at the first stimulation intensity for a third time period immediately following the second time period, wherein the second stimulation intensity is less than the first stimulation intensity, wherein each of the first time period, the second time period, and the third time period comprises at least five minutes, wherein the stimulation elicits a first inhibitory physiological response related to voiding in the patient during the first time period and elicits a second inhibitory physiological response related to voiding in the patient during the second time period, and wherein the second inhibitory physiological response is greater than the first inhibitory physiological response.

21. A computer-readable medium comprising instructions that cause a processor to:

receive via an implantable medical device an indication that a pharmacological agent has been administered in a dosage sufficient to desensitize a C-afferent nerve fiber to a patient in which the implantable medical device is implanted;

select an electrical stimulation therapy program based on the received indication; and

control a therapy delivery module to generate and deliver electrical stimulation therapy in accordance with the electrical stimulation therapy program to activate a nerve fiber proximate to the C-afferent nerve fiber, wherein the nerve fiber is different than the C-afferent nerve fiber, wherein the electrical stimulation therapy elicits an inhibitory physiological response related to voiding in the patient, and wherein the electrical stimulation therapy substantially does not activate the C-afferent nerve fiber after desensitization of the nerve fiber via the administration of the pharmacological agent.

22. The computer-readable medium of claim 21, wherein the nerve fiber forms a portion of at least one of a spinal nerve, a sacral nerve, a pelvic nerve, a pudendal nerve, dorsal genital nerve, a tibial nerve, an inferior rectal nerve, or a perineal nerve.

23. The computer-readable medium of claim 21, wherein the inhibitory physiological response comprises a reduction of a frequency of bladder contractions of the patient.

24. The computer-readable medium of claim 21, wherein the electrical stimulation therapy program defines a pulse frequency of the electrical stimulation therapy, and wherein the pulse frequency is less than about 60 Hz.

25. A system comprising:

means for administering a pharmacological agent to a patient in a dose sufficient to desensitize a C-afferent nerve fiber; and

means for delivering electrical stimulation to activate a nerve fiber proximate to the C-afferent nerve fiber via an electrode electrically coupled to the means for delivering stimulation, wherein the nerve fiber is different than the C-afferent nerve fiber, wherein the stimulation of the nerve fiber elicits an inhibitory physiological response related to voiding in the patient, and wherein the stimulation substantially does not activate the C-afferent nerve fiber after desensitization of the nerve fiber via the administration of the pharmacological agent.

26. The system of claim 25, wherein the nerve fiber is an afferent nerve fiber.

27. The system of claim 25, wherein the nerve fiber is an efferent nerve fiber.

28. The system of claim 25, wherein inhibitory physiological response comprises a reduction of a frequency of bladder contractions of the patient.

29. The system of claim 25, wherein the pharmacological agent comprises at least one of a sodium channel blocker, a calcium channel blocker, botulinum toxin, or capsaicin.

30. A system comprising:

means for receiving an indication that a pharmacological agent has been administered to a patient in a dosage sufficient to desensitize a C-afferent nerve fiber in the patient;

means for selecting an electrical stimulation therapy program based on the received indication; and

means for generating and delivering electrical stimulation therapy in accordance with the electrical stimulation therapy program, wherein the electrical stimulation therapy program is configured to activate a nerve fiber proximate to the C-afferent nerve fiber, wherein the nerve fiber is different than the C-afferent nerve fiber, wherein the electrical stimulation therapy elicits an inhibitory physiological response related to voiding in the patient, and wherein the electrical stimulation therapy substantially does not activate the C-afferent nerve fiber.

31. The system of claim 30, wherein the nerve fiber is an afferent nerve fiber.

32. The system of claim 30, wherein the nerve fiber is an efferent nerve fiber.

33. The system of claim 30, wherein the inhibitory physiological response comprises a reduction of a frequency of bladder contractions of the patient.

34. The system of claim 30, wherein the pharmacological agent comprises at least one of a sodium channel blocker, a calcium channel blocker, botulinum toxin, or capsaicin.