InterXClinic How does it work

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Monday - Friday: 9.00am – 5:30pm
105-107 Bath Road
Cheltenham GL53 7LE
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Interactive Neurostimulation with the InterX device

Pain relief

Physiological pathways of pain

Fig.1 Physiological pathways of pain (source:

To understand which mechanisms the InterX activates to provide pain relief lets look how the body generally mediates pain:

  1. When injury or trauma occurs, the first response is through sensitisation of special receptors of free nerve endings, called nociceptors. A delta and C fibres sense pain and temperature. They are situated in the skin and signal through the nerve pathways the central nervous system. Their cell bodies are in the dorsal roots of the spinal column.
  2. It synapses in the dorsal horn with a second-order neuron that immediately crosses the midline and ascends on the contralateral side in the spinothalamic tract. These axons are ending in Hypothalamus and Thalamus at the centre for autonomic regulation.  In the thalamus, some projections are made directly to the primary sensory cortex, whereas others go to the limbic system, which includes the insula, amygdala, and cingulate cortex.
  3. There, the neuron synapses with a second-order neuron, which projects to the primary sensory cortex.

The primary and secondary somatosensoric cortices are responsible for eliciting and localising pain stimuli and form the response conveying further through descending neural pathways:

  1. Somatosensoric tract, anterior insular and cingulated cortices and amygdala to mediate unpleasantness of pain;
  2. Further descending modulation of nociceptive information occurs through several nuclei in the midbrain, including periaqueductal grey;
  3. To the dorsal horn of the spinal tract and through A beta fibres to the injured area.

Somatosensoric cortex also involved in the inhibition of transmission of pain in the descending pathways either directly to the spinal cord via cortico-spinal tract or through thalamus or through periaqueductal grey.

 So far, various modalities have been used to reduce pain, for example, TENS works by high-frequency, low amplitude stimulation of larger peripheral fibres, and this inhibits transmission of pain through the “gates”. Dorsal Column Stimulation is similar, but works by antidromically stimulating the same A beta fibres. Acupuncture works in a different way: it causes low-frequency high amplitude stimulation of small A delta fibres (amongst other fibres), and this also causes inhibition of pain through gating mechanisms. Another difference between acupuncture and TENS is that the effect of acupuncture can be blocked by giving opioid antagonists, which don’t inhibit the effect of TENS.

The effectiveness on reducing pain from Interactive Neurostimulation is due to many, not just one mechanism for pain control.

The InterX is acting on the skin engaging neuro-immune-cutaneous-endocrine network (NICE). The impedance change triggers activation of autonomic response which retains the ability to respond to both endogenous and exogenous stimuli and operates through a release of Regulative Peptides (RP) and Neuropeptides (NP) . “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)

Mechanisms are most likely to employ the activation of natural descending inhibition of pain through the release of neurotransmitters of the central descending system within the spinal cord and spino-reticular-diencephalon pathway. Current scientific studies revealed pharmacological and anatomical pathways that mediate the reduction in pain produced by high and low frequencies with transcutaneous electrical nerve stimulation. This data suggests that the analgesic action produced through the action of different neurotransmitters and receptors.  Often pain associates with ongoing over activity of the sympathetic responses. Interactive neurostimulation causes deactivation of the sympathetic response through activating the parasympathetic nervous system.  Alongside mechanisms include:

  • down regulation of inflammation
  • improved microcirculation and as a result
  • cellular oxygenation and
  • enhancement of the energy (ATP) metabolism.

A recent study evaluating the effects of Interactive Neurostimulation indicates a positive activation of the immune system.

Let’s look what effects are frequently observed clinically from the treatment with the InterX:

  • Pain Relief: accumulative, ongoing prolonged – ‘stair-step’ process;
  • Autonomic response:
  • Sympathetic– initially, in most cases patients begin to perspire, heart beat and BP slightly increases, patients feel warm
  • Parasympathetic– after 10 to 15 minutes and onwards 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;
  • Function and a range of motion improvement 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)

The InterX produces high amplitude, high voltage and high frequency stimulation with pulsing current.  It has an interactive feedback through change of the skin impedance. More over this stimulation is delivered to a specific point of high sympathetic activity and the current density is very high insuring that all cutaneous receptors are stimulated.

Fig. 2 A pair of concentric electrodes are in direct contact with the target area

Fig. 2 A pair of concentric electrodes are in direct contact with the target area

Most crucial in the effectiveness of the electrical neural stimulation are the following:

  • It is necessary to produce a sufficiently high intensity of stimulation to be able to affect A delta afferent fibres. With regular TENS devices it isn’t possible to achieve stimulation of A-delta fibres, because the stimulation has to be beyond tolerable intensity level.  Interactive neurostimulation has an interactive feedback, it allows to adjust current (the amplitude) of the impulse at the points of low impedance without over-stimulating the nerve endings. Close positioning of both electrodes causes concentration of the stimulation to one point and this high density electrical current enabling sufficient intensity to stimulate A-delta fibres and interactive feedback enabling current adjustment without burning the nerve ending and pain.Fig. 3 Interactive waveform is impedance sensitive    Fig. 3 Interactive waveform is impedance sensitive
    Fig. 3 Interactive waveform is impedance sensitive


  • It is necessary to find the right place to treat, when the electrode is placed within the zone of the neuronal receptive field. The InterX has the ability to scan to detect the points of lowest impedance – the optimal points for treatment;
  • It is necessary to produce high and low frequency of stimulation to engage various neuronal pathways within the peripheral and central nervous system: descending inhibitory systems and the receptors at the site of injury. The InterX operates in wide range of frequencies from 15PPS to 480PPS with interactive pulsing waveform;
  • Lastly, tolerance to stimulation has to be overcome. Studies demonstrate that that ordinary TENS devices can be ineffective by the fourth day.3 The InterX utilises interactive neurostimulation, where feedback system modulates the electrical stimulus in response to the impedance change of the patient’s skin and underlying tissues, the latter controls output from the device by varying the voltage in order to maintain a constant peak current. Constantly changing signal prevents from accommodation to therapy.

Enhancement of the energy (ATP) metabolism

Any chronic inflammation accompanies by muscular spasm at the area of inflammation. Over time the shortened muscle exerts increasing tension on its tendon attachment to the bone, which gradually leads to the various tendonitis, bursitis and joint pain syndromes depending upon which muscle is shortened. Shortened muscles between vertebrae increase pressure and inflammation on discs, nerve roots and facet joints in the cervical and lumbar spine.

Healthy muscular cells contract and relax using the following mechanism:

  1. Efferent moto nerve cells communicate through repolarisation of the neural membrane. Neurotransmitter release (acetylcholine) leads to further depolarisation in the muscular cell membrane. This causes inside the muscle release of Ca+ release from the Sarcoplasmic Reticulum (ions of Calcium pool). High concentration of Ca+ inside the cell causes contraction of Actin – Myosin, making a muscular fibre to contract.
  2. After that Ca+ are pooled back into SR and the concentration of Ca+ reduces, this causes the muscular fibre to relax.

When there is a prolong inflammatory process, afferent sensory nerve cells are bombarded with signals of pain, the efferent moto nerve cells are activated causing the repolarisation of the neural membrane. Excess of Neurotransmitter Acetylcholine release leads to longer depolarisation in the muscular cell membrane. This causes a constant release of Ca+ ions from SR inside the muscle cell. High concentration of Ca+ inside the cell causes a prolong coupling of Actin – Myosin, making muscle fibres constantly contract.

Fig 4. Shortened muscle syndrome (source:

Fig 4. Shortened muscle syndrome (source:

Prolong Actin-Myosin coupling causing muscle to shorten, the fibres compress feeding blood vessels, this leads to reduced microcirculation with state of ischemia and lack of Oxygen (Hypoxia).

Without Oxygen, cells can not run glycolysis and its first product, pyruvate can not enter the mitochondria to metabolise down to water and energy (ATP). Hypoxia leads to accumulation of lactate in the cell. Anaerobic respiration is less efficient at using the energy from glucose since 2 ATP are produced during anaerobic respiration per glucose, compared to the 38 ATP per glucose produced by aerobic respiration. This leads to energy starvation.

Persistent contraction increases metabolism. Increased metabolism demands for energy and insufficient energy in the cell fails to re-uptake Ca+ into SR, which causes further increase of the concentration of Ca+ in the cell.   This is a continuing looping process, so called ‘energy crisis’. If muscle fibres are injured or deprived of energy supply, Calcium continues to concentrate in the cell cytoplasm and this persistent concentration leads to a sustained contraction of the muscular fibres. At this state no signals from the motor neurons come from the spinal cord. This is how trigger points are formed. One can detect these trigger points with the InterX as they normally have lower impedance and higher conductivity of the current and are tender to palpation.

To reverse this process various therapies are effective, including acupuncture, physical/manual therapy, TENS etc. The InterX is effective as it produces high density stimulation to the specific point – trigger point. The InterX employs various mechanisms for pain control and reduces ongoing peripheral sensitisation. Clinical observation and controlled studies define a high degree of the effectiveness of the InterX in muscular spasms reduction. Almost instant appearance of erythema (reddening of the skin) at the corresponding damaged areas demonstrates that that the InterX is stimulates microcirculation at the site of the injury/trauma, especially when dealing with ischemic tissues after prolong muscular spasm. In case of acute trauma and injury the InterX enhancing lymphatic circulation and one can actually observe and measure oedema reduction.6

Types of pain

Acute and chronic pain is different physiologically. Clinicians should recognise and treat them accordingly. Acute pain originates because of direct damage to tissue or trauma and serves a protective purpose throughout the healing process.
InterX is most effective in management of acute post operative pain. There are few controlled studies produced to prove the effectiveness in treating patients post operatively. The fact that Interactive neurostimulation does not have side effects compared to opioids and is effective without causing tolerance compared to TENS could be promising for post operative pain management. InterX stimulation is limited to dermis, it is not transcutaneous and it does not cause muscular contraction, it could be safely used over internal metal work, for example, replaced joints.

Fig 5. Gradual pain reduction over a period of time

Fig 5. Gradual pain reduction over a period of time

Treatment of acute pain will require higher amplitude and frequency of pulse stimulation and will have a sedative effect on the nerve endings.  In case of acute pain from injury treatment could be used as often as every two hours to produce the best effect.

Chronic pain does not have a protective meaning and typically progressed from acute pain when the body for some reason does not complete the healing within regular biological time. Chronic pain typically originates in deep tissue from the muscles, joints or viscera, which is not necessary located at the site of injury and can be referred. For example, in patients with osteoarthritis pain is referred and involves muscles that are outside of the injury. Treatment of chronic nociceptive pain requires understanding and treatment should be addressed not only to the primary site of pain, but also to the corresponding segment, dermatome. Stimulation should be at a lower level intensity as the receptors are already sensitised. Treatments should be less frequent because the body adapts to ongoing chronic inflammation. Choice of frequency of the pulse should be within the lower band, because it is necessary to produce gentle stimulation in order to complete the inflammatory phase, the application frequency should be less as the InterX can cause unnecessary aggravation, therefore the whole treatment process should be gradual. Every treatment session is aimed to retrain the nervous system from ongoing sensitisation.

Neuropathic pain is due to dysfunction of any of components of the nervous system. All the causes could be divided by the type of the pathological process at different levels. Neuropathic pain could be caused by central, peripheral sensitisation, reduced inhibition or sympathetic activation.

  • Central sensitisation occurs after the injury to the peripheral nerve and is caused by the changes within the dorsal horn – hypersensitivity of dorsal horn neurons;
  • Disinhibition – reduced activation of the descending inhibitory systems which is normally modulated through endogenous opioids, serotonin, norepinephrine, etc. Could be a result of the loss of input into the dorsal horn;
  • Sympathetic activation, where the sympathetic nerve passes information to the nearby blood vessel towards the site of injury can enhance the signal transmission to the dorsal root ganglion;
  • Peripheral sensitisation caused by hyperexcitability of the peripheral nerve that is injured with a release of inflammatory mediators and due to the altered functioning of sodium and calcium cannels causes ongoing sensitisation of the adrenergic receptors in peripheral nerve and dorsal root ganglions.

Understanding these mechanisms in management of neuropathic pain with the InterX is paramount. Success of the treatment very much depends on the treatment planning, for example, choice of zones for application of the InterX is totally different than in treatment of nociceptive pain. It is important to treat specific nerve points, that are systemic and coincides with the points of acupuncture and trigger points.10 Choice of frequencies is important and should use both low and high frequency to engage various mechanisms for pain inhibition, but with minimal intensity as in case of peripheral sensitisation it can promote further release of inflammatory mediators and worsening pain for the patient. Frequencies of treatment procedures are also differ from the regular treatment protocol.
Fig. 6 Sympathetic inflammation

Careful planning and complex approach in treatment of neuropathic pain is important to secure success in treating patients with severe neuropathic pain. Dealing with chronic neuropathic pain requires patience, treatment typically is long term and includes few courses of treatments to achieve a gradual, over period of time reduction of symptoms. Overall, use of the Interactive neurostimulation should be considered in management of chronic neuropathic pain.  This form of neural stimulation does not have side effects and is clinically proven to give superior results to other standard therapeutic approach.


To summarise, the design and interactive waveform of the InterX allows the therapist to deliver patient specific treatments and enables an entirely different treatment approach. Treatment can be applied locally, to the dermatomes, over orthopaedic metal implants and directly over the spine, the face and scalp using InterX protocols:

  1. SCAN (without gel) to identify the right place to treat anywhere on the body including the spine and face. InterX identifies points of low impedance;
  2. TARGET Stimulation is delivered using high amplitude, high density current
    – Amplitude = 35-60mA on skin (compared to 15-40mA with TENS)
    – Current Density = 170-220mA per square inch, (compared to 5-12mA with TENS)
    with a wide range of low and high frequencies – 15 – 480 pulses per second;
  3. DYNAMIC Perform therapeutic exercise while treating the area. Interactive, variable waveform and short treatment protocols avoids nerve and physiological tolerance/accommodation.

The design of the flexible array electrodes ensures that the most treatment is delivered to areas of low impedance. The low impedance on the skin is caused by an increase in the sympathetic skin response and research shows that these points correlate to myofascial trigger points and major nerve branches. Cutaneous stimulation does not cause muscular contraction and the InterX is safe to use over internal metal work.

In this article the author outlines own view and hypothesis of the mechanism of action based on available research sources. Further scientific studies are necessary to identify all mechanisms of the effectiveness of the interactive neurostimulation and further clinical studies with larger number of patients that could identify further claims in use of the InterX device.

* Contemporary Management of Neuropathic Pain for the Primary Care Physician’ review. H. Chen, T. Lamber, R. Rho, K. Marchall, T. Sitzman, S. Chazi, P.Randall, Brewer. December 2004 Mayo Clinic
* Rawal N, Ann Med Apr 1995 27(2) 263-8pp].
* Neuronal Control of Skin Function. The skin as a Neuroimmunoendocrine Organ’ R. Dirk, T. Goerge, S Schneider, N.  Bunnett, M. Steinhoff. Physiol. Rev. 86 1309 – 1379; 206
* Mechanisms and Management of Pain for the Physical Therapist’ Kathleen A. Sluka, 2009, 171 – 180
* EEG study report, (not published, available from author)
* Gorodetskyi IG, Gorodnichenko AI, Tursin PS, Reshetnyak VK, Uskov ON. Non-invasive interactive neurostimulation in the post-operative recovery of patients with a trochanteric fracture of the femur. J Bone & Joint Surg 2007;89-B:1488-94.
* Gorodetskyi I.G. et al, The effects of non-invasive, interactive Neurostimulation on pain and edema during post-surgicalrehabilitation following external fixation of unstable bi-malleolar ankle fractures. Presented as a poster by Dr James Dillard at the IASP 2008, Glasgow, Scotland
* An Abstract: Scientific research to examine the physiological effects ofInterX Therapy in humans This abstract has been submitted as a plenary lecture at the International Association of the Study of Pain (IASP) in Montreal 2010.
* Maale G, Gamez M. The effects of a handheld, cutaneous, portable, neuro stimulator using two concentric conductive electrodes with signals that are damped, biphasic oscillatery cuneiform, which use skin as a conduit in patients with severe chronic pain from large orthopedic procedures. 18th Annual Symposium International Society for Technology in Arthroplasty, 2005:143


– ‘Biomedical Acupuncture for Pain Management: An Integrative Approach’ Yun-Tao Ma, Mila Ma, Zang Hee Cho, 2005, 19- 30