DARPA  -  Persistence in Combat 
		  Pre-solicitation Proposal

Electro-Pulsed Pain Inhibition
A Non-Pharmacological, Non-Sedating Approach

Submitting Organization: 

MindTel, LLC.
Dave Warner, MD, PhD. – Director
P.O. Box 8995
Rancho Santa Fe, CA. 92067
davew@well.com
 
Budget:  $1,300,000 over 3 years	

Phase 1  ---	$400,000 fiscal year 2002
		Phase 2  ---	$400,000 fiscal year 2003
		Phase 3  ---	$400,000 fiscal year 2004

Proposal Summary:

Post injury pain perception (nociception) can be a limiting factor in the completion of any physical task.  The elimination or reduction of these objectionable neural sensations before reaching higher cortical processing centers in the brain is the purpose of this investigation.  While pharmacological intervention is effective in this area, our approach seeks to bypass a number of acute side-effects such as sedation and respiratory or cardiac irregularities, which may exacerbate the limitations of an injured warfighter in the military theatre.  We will research and test a number of established and theoretical electronic apparatus modalities that inhibit the perception of pain via neural stimulation. 

Personnel Alliances:

W. Ross Adey, MD		-  EM/Cellular Membrane Researcher		

Edward Lipson, PhD.       	– Physics Professor, Syracuse University

Francisco Sanchez, DVM  	– Surgeon, Minimally Invasive Surgery Center (MISC)

Bill Rojas, PhD.                      – EEG and Electrode Design Technician

Barry Sterman, PhD.               – UCLA/VA Neuro-biofeedback Researcher

Focus:

Our research will focus on a nerve cells ability to be entrained or coupled to the rhythmic pulses of an external stimulus of electro-magnetic (EM) origin.  This interaction of EM waves with cellular membranes has been determined to be of a non-linear nature (solitons) providing for small amounts of energy appropriately delivered to produce significant changes within the cell body. This interaction has many theoretical possibilities for external manipulation of surface proteins and voltage-gates which regulate chemical pumps and cellular firing patterns.  The comprehensive understanding of this phenomenon from a molecular perspective will allow us to outline an Electro-Pulsed approach to the neural manipulation of Pain Inhibition.    

Pain Inhibition:

Any nociception inhibition paradigm depends on understanding the chemical flux rhythms of natural pain mediation within neural pathways such as the A-Delta (acute – sharp and piercing) and C-Polymodal (chronic – burning and throbbing) fibers.  These electro-chemical pathways play a post-injury role regulating pain sensation with regard to sodium/potassium pumping, calcium efflux, GABA, Substance P, and endorphins  The ability to stop or reduce the propagation of action potentials along pain pathways is facilitated by the release of interneuron enkephalins (Met and Leu).  These, 5 amino acid long chains, bind to Mu (u) receptors and hyperpolarize the nerve cell limiting nociception in the brain.  

Mu, Delta and Kappa receptors are believed to hold the most promise for future investigation.  Activation of Mu and Delta receptors with opiates is reflected in a dose-dependent reduction in pain and nociception-related behavior. The Kappa receptors are believed to be associated with many opioid side effects, although a number of effective analgesics act primarily at these sites.  

Neural Entrainment:

Adey et al have documented neural entrainment via sympathetic resonance with a pulsed EM stimulus.  Consultation with biological and theoretical experts in various fields will prove invaluable to our experimental protocols.  As one potential method of Electro-Pulsed Pain Inhibition we will investigate the electroencephalographic (EEG) waveform dynamics of interneurons as they release their analgesic Met and Leu enkephalin pentapeptide ligands.  A Fast Fourier Transform (FFT) analysis of these neural signals will provide insight into the cells depolarization and wave characteristics (frequency, amplitude, duration, and harmonics) by which a suitable EM wave can be experimentally designed.  By designing waveforms which mimic the naturally occurring characteristics of neural activity, pulsed EM energy may be delivered to the appropriate mediating pathways within the brain and spinal column and inhibit the sensation of pain after injury.

Proposed Tasks:  

Phase 1 - We will design an experimentation protocol based on the following:    

A) Consultation Compensation: $100,000

1) Consult with Dr. Adey for insight and equipment possibilities	-  20,000
2) Consult with Dr. Lipson for theoretical physics possibilities	-  20,000
3) Consult with Dr. Rojas for EEG and electrode design		-  20,000
4) Consult with Dr. Sanchez for animal related studies		-  20,000
5) Consult with Dr. Sterman for bio-feedback related studies  	-  20,000

B) Animal subject screenings and EEG recordings: $150,000

1) Screen and select animal models					-  25,000
2) Test and Purchase EEG Equipment				-  75,000
3) Test and Manufacture Recording Electrodes			-  15,000
4) Analysis of EEG Recordings					-  10,000
5) Design Bio-Mimetic Waveforms					-  15,000

C) Stimulation Apparatus: $150,000

	1) Test Stimulating Equipment – animal model			-  25,000
	2) Purchase Stimulating Equipment 				 	-  75,000
	3) Test Stimulating Electrodes					-  15,000
	4) Purchase/Design Stimulating Electrodes				-  35,000

D) Animal Model Research: $100,000							

Phase 2 –  Human Model Research – $400,000

Phase 3 -  Warfighter Equipment Customization  and Miniaturization – $400,000