An effective, quick-acting and quick-reversing means of blocking the conduction of action potentials in whole nerve would have many important clinical applications, such as the elimination of pain and the modulation of muscle spasticity. One potential method for achieving this type of nerve conduction block is to use high frequency alternating current delivered through electrodes surrounding the target nerve. In our currently funded project, we have determined that this method can block 100% of the motor response in motor nerves. The block is gradable and can be completely reversed within one second. We are now ready to take the next step toward practical clinical implementation of this technique. Therefore, the specific aims of the proposed project are to: 1) determine if the chronic block of nerve conduction is damaging to the nerve, 2) determine the specific parameters necessary to provide motor and sensory block in humans, and 3) complete the technical and regulatory effort necessary to proceed to widespread human application of this technique. Chronic nerve block will be applied to the peripheral nerves of dogs for four weeks using parameters and regimens based on anticipated human applications. The post-operative nerve histology will be the primary outcome measure that will be used to determine if there are any damaging effects of the chronically applied conduction block in-vivo. We expect that the conduction block will not damage peripheral nerve because it uses a very low charge delivery per phase and delivers a zero net charge to the tissue. In conjunction with the chronic animal study, we will commence acute human studies using: 1) explanted human nerves to determine the parameters necessary for conduction block in large diameter nerves, 2) acute intra-operative testing to determine if successful motor block can be accomplished in the presence of intact reflex circuits, and 3) short-term chronic experiments to determine the parameters necessary for complete pain block. At the end of the proposed three year project, we expect to have completed all of the necessary tasks to enable the application of electrical nerve conduction block in humans for the elimination of peripheral nerve pain and for the modulation of muscle spasticity. This research will provide a significant tool in our ongoing efforts to reduce disability and improve quality of life.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002091-05
Application #
6889999
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Peng, Grace
Project Start
2001-06-15
Project End
2007-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
5
Fiscal Year
2005
Total Cost
$307,230
Indirect Cost
Name
Case Western Reserve University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Vrabec, Tina; Bhadra, Niloy; Wainright, Jesse et al. (2016) Characterization of high capacitance electrodes for the application of direct current electrical nerve block. Med Biol Eng Comput 54:191-203
Franke, Manfred; Bhadra, Niloy; Bhadra, Narendra et al. (2014) Direct current contamination of kilohertz frequency alternating current waveforms. J Neurosci Methods 232:74-83
Kilgore, Kevin L; Bhadra, Niloy (2014) Reversible nerve conduction block using kilohertz frequency alternating current. Neuromodulation 17:242-54; discussion 254-5
Peckham, P Hunter; Kilgore, Kevin L (2013) Challenges and opportunities in restoring function after paralysis. IEEE Trans Biomed Eng 60:602-9
Foutz, Thomas J; Ackermann Jr, D Michael; Kilgore, Kevin L et al. (2012) Energy efficient neural stimulation: coupling circuit design and membrane biophysics. PLoS One 7:e51901
Bryden, Anne M; Peljovich, Allan E; Hoyen, Harry A et al. (2012) Surgical restoration of arm and hand function in people with tetraplegia. Top Spinal Cord Inj Rehabil 18:43-9
Boger, Adam S; Bhadra, Narendra; Gustafson, Kenneth J (2012) High frequency sacral root nerve block allows bladder voiding. Neurourol Urodyn 31:677-82
Ackermann, D Michael; Bhadra, Niloy; Gerges, Meana et al. (2011) Dynamics and sensitivity analysis of high-frequency conduction block. J Neural Eng 8:065007
Foldes, Emily L; Ackermann, D Michael; Bhadra, Niloy et al. (2011) Design, fabrication and evaluation of a conforming circumpolar peripheral nerve cuff electrode for acute experimental use. J Neurosci Methods 196:31-7
Ackermann Jr, D Michael; Bhadra, Niloy; Foldes, Emily L et al. (2011) Conduction block of whole nerve without onset firing using combined high frequency and direct current. Med Biol Eng Comput 49:241-51

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