InterX - How does it work

The InterX device provides Non-Invasive Interactive Neurostimulation therapy (NIN).
NIN is an advance form of neurostimulation aimed at treating both Acute and Chronic pain.

NIN is an advance form of neurostimulation that integrates into existing treatment programs to enable enhanced results in treating both Acute and Chronic pain. This stimulation has an interactive nature: each consequent signal from the device communicate with the nervous system through the skin interface.

Therapy's goal is to decrease pain, increase Range of Motions and accelerate return to full function.

Clinical Trials have shown:		Reduced Pain
		Increased ROM
		Reduced Edema
		Improved tissue healing

Impulse
The InterX device delivers pulsing electrical stimulation to the skin of the patient (Fig 1.).

Pulsing electrical stimulation (Fig.1)

The device generates high amplitude, low average current, damped biphasic electrical impulses that are delivered to the tissue via a pair of concentric electrodes placed in direct contact with the target area (see Fig.2).

The device generates high amplitude, low average current, damped biphasic electrical impulses (Fig.2)

Waveform
The waveform is tissue impedance sensitive, hence voltage, frequency and damping of each biphasic impulse changes in relationship to the impedance of the underlying tissue (Fig.2) resulting in a highly sensitive, highly variable voltage in order to maintain constant peak current.

Skin contact: waveform is impedance sensitiv(Fig.3)

The precise biochemical mechanism of action for NIN has not yet been proven.  However, clinical observation of human response to treatment suggests the release of neuropeptides and cytokines having regulative effect on the body.

These are the effects we observe clinically:

	Pain Relief - accumulative, ongoing prolonged – ‘stair-step’ process
	Autonomic response
	Sympathetic response – at first in most cases patients begin to perspire, heart beat and BP slightly increases, patients feel warm Parasympathetic response – after 15 to 20 minutes of stimulation most patients become relaxed, sleepy, heart beat slightly decreases, BP normalises;
	Post treatment – most patients report having prolonged deep sleep ‘first time in years’
	Range of motion increases due to Muscular relaxation
	Microcirculation – increased - under the electrode one can see erythema after a few minutes of application
	Functional restoration before full pain relief
	Feeling of well-being, feeling light, warm, relaxed, sleepy, but not tired;
	Inflammation decreases (over a period of time)
	Reversal of the symptoms (over a period of time)

How those effects are achieved ?


The InterX device delivers pulsing electrical stimulation to the skin of the patient. This stimulation has very low depth of penetration and is only limited to the epidermis/dermis of the skin.

There are few aspects of the impulse that makes this therapy stand out:

1. Variety of stimulation.

Each generated impulse combines a variety of current characteristics: DC and AC millicurrent followed by AC microcurrent. Such a variety of stimulation cause multiple responses from the patient’s body, including cellular (Okihana,Uchida, Shimorura, 1985), (Reger et al.,1999). The stimulation affects all structures of the skin under the electrode including nociceptors;

The impulse parameters are controlled by the change in patient’s skin impedance. the following: amplitude - Voltage, Frequency of the oscillations within each pulse and Damping of the waveform are impedance sensitive. Stimulation from the InterX is very targeted and precise; the areas of the skin that have regular parameters, i.e. non-affected by the trauma or inflammation remain the same, only the areas of low impedance receive a therapeutic stimulation.

2. Inflammation or injury impacts the skin impedance:

	Trauma or inflammation impacts on the corresponding sympathetic nerve. With the increase of the sympathetic nerve activity, local blood circulation and the release of pro-inflammatory cytokines in the underlying tissue increases affecting the Galvanic current;
	The increased Galvanic response causes an increased sweat secretion; and this lowers the impedance of the skin;
	InterX is impedance sensitive and can therefore be used to scan for the optimal treatment points (Shah, Phillips, Danoff, Gerber, 2005), (Shultz, Driban, Swanik,2005)

3. Those Impedance changes are linked to Autonomic regulation; Skin is a Neuro-Immuno-Cutaneous-Endocrine interface (NICE) (O’Sullivan R., Lipper G., Lerner E., 1998), which retains the ability to respond to both endogenous and exogenous stimuli.

	Body response to stimulation involves NICE network and operates through a release of Regulative Peptides (RP) and Neuropeptides (NP)
	Locally – area of the skin/ underlying tissues related to inflammatory process or injury;
	Centrally CNS:
	segmental - spine; brain
	Bi-directional response. Autonomic regulation to pain/inflammation through Central Nervous System. There are few references supporting this evidence below.
	“The Autonomic Nervous System has two principal divisions, the parasympathetic pathway and the sympathetic pathway which act either in synergy or in opposition to mediate basic physiological responses in real time” “The Autonomic Nervous System interacts with the primitive brain, Brain Stem and Hypothalamus. Hypothalamus neural output is relayed to sympathetic and parasympathetic nuclei in the brain stem and Spinal cord. Hormonal input also controls the release of pituitary hormones, which in turn regulate the basic functions of endocrine organs” (Tracey K ”The inflammatory reflex”) “Disruption of homeostasis by injury activates programs of neural, hormonal and behavioural activity aimed at a return of homeostasis. The particular programs that are activated are selected from a genetically determined repertoire of programs and are influenced by the extent and severity of injury” (R. Melzac 1999) “The skin, the nervous system and immunity are not independent systems but are closely associated and use the same language of cytokines and neurotransmitters” (L. Misery 1998) “Recent studies indicate that NP released by cutaneous nerves such as c-fibres can activate a number of target cells including keratinocytes, Langerhans cells, mast cells, and endothelial cells (IL1, IL8, TNF, HDMEC, CGRP, VCAM-1)” “The neurologic system mediating the biological processes that occur during inflammation and wound healing in the skin” (Ansel J., Armstrong C., Song I., Quinlan K., Olerud J., Caughman S., Bunnett , 1997) “The pattern, duration, and frequency of stimulation will determine the simultaneous or selective release of neuropeptides or transmitter. Neuropeptides may sometimes act as neurotransmitters, neuromodulators, or neurohormones, depending on the synapse or tissue.”( F.L. Strand 2002)

4. The Russian animal model study, where the EEG was recorded to see any difference before, during and after the stimulation, shows an increase of the alpha activity of the cerebral cortex (optic area) which reflects an increase in activity of the anterior hypothalamus and synchronisation only after 10 minutes of stimulation. (Chebkasov S., BereshpolovaY, 2000)

5. In the Australian animal model study, healing of the Medial Collateral Ligament under NIN stimulation was studied in comparison with the control group, where VEGF, PCNA protein expression together with histological improvement in tissue organisation was noted. (Walsh B, Oliver R, Vizesi F, Yu Y, Mitchell G, Rawlinson J. 2007)


Based on clinical observation, suggested hypothesis is that all observed treatment outcomes from the InterX, in particular unusually powerful and sustained pain relief, and positive impact on healing as well as function regulation are due to complex ‘systemic’ body response via active involvement of the Central Nervous System of the patient.