The Human Body
A Scientific & Historical Review
Victor I. Chornenky, Ph.D.
Minnesota Medical Physics, LLC
Electromagnetic Fields and Human Body
A Scientific & Historical Review
Victor I. Chornenky, Ph.D.
One of the most important discoveries in physiology over the last forty years is the effect of Electromagnetic Fields (EMF) on the development of new and the repair of damaged tissues. While the currently available EMF therapy is confined to treatment of non-healing bone fractures and wound healing, it is generally recognized that non-invasive EMF therapy might have a much broader clinical potential. The field of application of EMF therapy was limited mainly because its biological and physical mechanisms were not fully understood and optimized methods of treatments were not yet developed. Interaction of EMF with biological cells and tissues continues to be studied in many biomedical laboratories around the world and its mechanisms are being better elucidated. Research is underway in several different areas: interaction of EMF with receptors of the cellular membranes and intracellular structures, the nature of biological signaling inside the cells and EMF driven genes activation and production of new proteins, other biomolecules and regeneration of tissues, and clinical effects of EMF.
Also, under development are medical devices with different configurations and specific properties of EMFs as well as different methods of their applications to various medical conditions.
Comprehensive understanding of the mechanisms of action of EMF presented significant challenges but recent progress promises various future EMF therapies for the treatment of different ailments and disease states. These new EMF therapies are expected to be more efficient, having fewer side effects and lower costs.
To understand where EMF therapy is today and what it can potentially bring tomorrow, it is instructive to follow the history of interactions of EMF with human body.
Different effects of electric energy on the human body have been witnessed since the middle of seventeenth century when the Leyden jar and methods of accumulating significant electric charges were discovered. In 1776, in a presentation to the French king Louis XVI on the effect of electricity, 180 royal guards holding hands in a long line simultaneously leaped as they were shocked by the electric discharge from a Leyden jar. The king was amused! Historically this demonstration was the first controllable interaction of the electric field with the human body. What started as entertainment opened a pipeline of fundamental discoveries about electricity in the human body and the effects of external and internal electric fields.
The first major finding was made by the Italian scientist Galvani, who discovered that the muscle contraction can be caused by electrical signals. In his famous experiments with a frog leg, he demonstrated that the leg jolted every time when an electric discharge was applied from a Leyden jar or another source of electricity.
Over the last two centuries, following the Galvani’s discovery, the electrical nature of the skeletal muscles, heart, nerve system, and brain were studied in detail. This ushered the development of the multidisciplinary science of human electrophysiology and neurology and a plethora of discoveries by biomedical scientists, which now are widely used in medicine.
The fundamental source of the electric fields in tissue, on a cellular level, is a plurality of molecular pumps on the membranes of the cells that pump K+ and Na+ ions in and out of the cells in unequal amounts (3Na+ out per each 2K+ in). This inequality creates a potential difference between the cytoplasm of the cell and the intercellular space, which is called trans-membrane potential. It is different for different type of cells and is in the range of -70 mV to -90 mV. The potential value is maintained by an appropriate rate of pumping of the ion pumps and by drainage channels that allow a free reverse drift of K+ and Na+ ion through the membrane. The pumps are made of complex protein macromolecules that consume energy from adenosine tri-phosphate hydrolyzation, which in turn, gets its energy from molecules of glucose inside the cell. Ultimately, this cellular molecular machinery converts the glucose energy into easily consumable electric energy.
The cellular membranes separating the inner negatively charged space of the cell, cytoplasm, from the positive intercellular space, are made of dielectric lipids and are surrounded on both sides by electrically conductive fluids. The positive ions from the intercellular fluid are attracted to the membrane and compensate the electric field anywhere outside the cell but in the thin lipid membrane itself. That makes the electric energy available only to the protein molecules that are imbedded in the cell membrane and have access to both positively charged extracellular space and negatively charged cytoplasm on their opposite ends. In this case K+ and Na+ ion pumps create only trans-membrane potentials; no electric field is created inside the cell or outside within the tissue. Significant electric field exists only in the nanometers thick lipid membranes and has consequences only for the membrane bound receptors and macromolecules.
The invention of Na+ / K+ ion pumps and electrical polarization of cell membranes is a great feat of nature. The pumps consume chemical energy and supply membrane bound machinery of the cell with easily available electric energy. They are a biological DC electric power plant of the cell. Hundreds of thousands of protein molecules imbedded in the cellular membrane perform transport of different ions and molecules in and out the cell. They consume the electric energy provided by Na+ / K+ ion pumps and make the transport and overall metabolism of the cell much more efficient. All biological cells in nature have this outstanding feature.
Du Bois-Raymond, a German scientist who discovered the action potential in nerves and is called the farther of electrophysiology, discovered in 1860 another new phenomenon in bioelectricity referred to as injury potential in human skin. In his experiments he observed, for the first time, the trans-epithelial potential (TEP), a potential difference of about +50 mV between the epidermis and endodermis of the human skin.
However, at the time its discovery, TEP phenomenon was marginally acknowledged, and almost forgotten until the middle of 20th century, when interest in TEP was revived. Since then, several research groups have clarified the role of TEP in the process of wound healing and came up with an idea of possible acceleration of the healing by exogenous electric fields.
In recent experiments, it was demonstrated that TEP across the epidermal epithelium is created by K+ / Na+ ion pumps. In this case, basal membranes of a layer of cells are aligned and connected to each other by tight links that prevent leaking even small molecules and ions. This high-resistance insulating layer maintains a constant potential between the epidermis and endodermis. Any damage to this layer leads to short-circuiting of TEP and production of extracellular currents at the edge of the wound. The densities of these currents are up to 300 µA/cm2 and the magnitudes of corresponding electric fields could be as high as 200 mV/mm. Importantly, it was found that this electric field contributes to a healing process by sending biological signals to the adjacent cells that trigger their proliferation and migration from the edge of the wound to its center. Furthermore, it was shown that the field activates the immune system, particular lymphocytes, locally boosting phagocytosis of alien microbes and dead cells and, as a result, protecting the wound from infection. Contrary to a microscopic membrane of a stand-alone cell, TEP is a macroscopic structure that continuously covers the whole human body. It functions both as a monitor of the skin integrity and the first responder in case of its compromise. The injury currents start instantly after injury and continue until the skin defect is repaired.
It was also discovered that the healing of an injured tissue is impeded or becomes incomplete if the injury currents have lower than usual magnitude. This phenomenon suggested a rational for applying electrical stimulation to non-healing wounds with the hope that it might initiate and accelerate the healing process. Clinical trials confirmed that expectation. Moreover, the clinical trials demonstrated that not only DC currents but also alternating high and low frequency currents can be effective in performing the healing task. Several of these systems are already FDA approved and available for treatment of non-healing wounds.
In the middle of 20th century, several scientists in Japan and USA discovered the newest bioelectrical phenomenon related to tissues in the human body. The essence of the discovery is that in some tissues a mechanical stress generates an electric field. This effect is especially noticeable in bones and cartilages. In this case, the electric field is present in the whole volume of stressed tissue. Molecular ion pumps discussed above do not produce this electric field; the nature of t8his phenomenon is completely different. Two other physical mechanisms are responsible for this electric field: a piezoelectric effect and a streaming potential effect.
The piezoelectric effect is the ability of some materials to generate an electric field in response to applied mechanical stress. Piezoelectric effect has been observed in a number of soft and hard tissues (including bone and cartilage) and appears to be associated with the presence of oriented fibrous proteins such as collagen. A deformation of a protein molecule produces asymmetric shift of the opposite electric charges in the molecule and results in a macroscopic electric field in the stressed tissue.
The streaming potential is produced when a liquid is forced to flow through a capillary or porous solids (including bone and cartilage). The streaming potential results from the presence of an electrical double layer at the solid-liquid interface. This double layer comprises of ions of one charge type which are fixed to the surface of the solid and an equal number of mobile ions of the opposite charge which are distributed through the neighboring region of the liquid phase. A mechanical stress applied to such a system creates a flow of the mobile ions with respect to the fixed ions on the solid surface, which constitutes an electric current. The electric potential in the tissue generated by this current is called a streaming potential.
In a real life both these mechanisms work simultaneously and produce a substantial stress generated potential (SGP) in bones and cartilages. It came as a surprise to scientists that SGP turned out to be an important part of bone and cartilage physiology – the adaptive remodeling. The fact that bones experience remodeling to adapt to the loads they are placed under, is well known from the 19th century (Wolff’s law). If loading on a particular bone or a section of bone increases, it acquires more calcium and becomes stronger, and vice versa: if the loading decreases, the bone loses its calcium and becomes weaker. This process is a particular problem in space, where due to the weightlessness the astronauts can lose strength of their bones to a level that impairs their ability to efficiently perform assigned tasks and jeopardizes their overall general health. The bone loss increases risk of bone fracture and kidney stones. Significant problems also arise after astronauts return to the Earth gravity when renewed load on the bones overwhelms the adaptation system.
Bone remodeling is a continuous process where mature bone tissue is removed from the skeleton (bone resorption) and new bone tissue is created (bone formation). These two processes also control the change of shape or replacement of bone following injuries like fractures or micro-damage occurring during normal activity.
The cells responsible for bone metabolism are known as osteoblasts, which secrete new bone, and osteoclasts which break down old bone. Generally, the bone metabolism is very powerful and efficient in maintaining strength of the bones to the very old age. However, an imbalance in the regulation of bone resorption and formation can lead to metabolic diseases, such as osteoporosis.
Articular cartilage provides frictionless motion of adjacent bones against each other. It is functionally and physiologically connected to the underlying bones and also participate in the remodeling process. However, a significant difference in remodeling opportunities exists between the bone and cartilage. Contrary to bones having ample blood supply, the cartilage has no blood supply at all. In its metabolic needs it relies upon diffusion of both the nutrients from the blood vessels surrounding the joint and the metabolic waste back from the cartilage to the blood vessels. Diffusion over significant distances is a slow process, a “bottle neck” of cartilage metabolism. In addition to that the cartilage has only one type of cells – chondrocytes, which perform both functions of resorption of old cartilage and creation of new one. This functional overload of chondrocytes leads to even slower remodeling of the healthy and repair of the damaged cartilage. To make things worse, impaired metabolism decreases viability of chondrocytes, especially in the inflamed arthritic joints. In this case a significant number of chondrocytes incurs apoptosis (programmed death) and, as a consequence, production of new cartilage decreases and balanced remodeling process turns into steady deterioration.
It has been shown in many studies that SGP plays a significant role in cartilage growth, repair, and remodeling. Moreover, it has become increasingly evident that SGP provides a link between physiology and physics that opens a new opportunity of influencing biological processes in the articular cartilage. It is now universally accepted that an increase in chondrocytes cell division and collagen and proteoglycan synthesis are possible and may be achieved in vivo by the application of an electric field.
In 2007, Japanese scientists (Tatsuta Hojo et al “Effect of heat stimulation on viability and proteoglycan metabolism of cultured chondrocytes”) made an important discovery. The authors demonstrated that exposure of cultured chondrocytes to elevated temperatures had two profound effects on the cells: it increased both their viability and proteoglycan metabolism. In contrast to the control cultures kept at 37o C, the cells exposed to elevated temperatures up to 42o C had significantly higher number of survivors 72 hours after exposure. In addition, they had significantly higher level of proteoglycans found both inside and outside cells. At temperatures above 43o C the cells had both lower viability and metabolism.
In another publication, Hitoshi Tonomura et al demonstrated that heat stimulation of rabbit articular cartilage in vivo caused increase in expression of extracellular matrix genes of proteoglycan core protein and type II collagen, the major structural components of the cartilage. (“Effects of heat stimulation via microwave applicator on cartilage matrix gene and HSP70 expression in the rabbit knee joint”)
The first successful therapeutic application of pulsed electromagnetic fields was the treatment of non-union fractures, the bones that did not heal despite repeated surgical procedures. The PEMF therapy for treatment of non-union bones was pioneered by Bassett et al. It is FDA approved and for many years successfully used in clinical practice.
From review of medical literature over the last decade, it is logical that the next significant PEMF application will be osteoarthritis treatment.
Recently a major breakthrough in understanding of PEMF action on a cellular level was reported by a group of Italian pharmaceutical and biomedical scientists. This group studied anti-inflammatory mechanism of PEMF action on number of cells found in arthritic joints. (Katie Varani et al. “Characterization of adenosine receptors in bovine chondrocytes and fibroblast-like synoviocytes exposed to low frequency low energy pulsed electromagnetic fields”) and (“Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils”)
In 2008, Frederica Francesca Masieri Doctoral dissertation “New insights and possible therapeutic implications of adenosine analogs and pulsed electromagnetic fields (PEMF) in osteoarthritis pathologies” concluded that PEMF can significantly inhibit the release of inflammatory parameters and established a link between PEMF stimulation and adenosine pathway known for its anti-inflammatory actions.
In series of experiments, the authors demonstrated that the PEMF target on the cellular level is adenosine receptors A2A and A3. These receptors were activated by PEMF in chondrocytes and
synoviocytes – the major cells present in joints. Receptor A2A only was activated in neutrophils – immune system cells that migrate from blood into arthritic joints, promoting inflammation. The anti-inflammatory action of PEMF via adenosine pathway manifested itself in chondrocytes and synoviocytes by suppressing cellular release of pro-inflammatory biochemical agents. This action inhibits cellular activity causing cartilage degradation and promotes production of new cartilage tissue. In neutrophils via adenosine receptor A2A PEMF induces apoptosis (programmed cell death) that directly modulates inflammatory stimulus by reducing number of neutrophils in the joint.
For more than a century, the pharmacologic management of osteoarthritis comprised usage of NSAIDs (non-steroidal anti-inflammation drugs), aspirin and COX-2 inhibitors. However, serious side effects, such as intestinal bleeding, cardiovascular problems and renal failure, limit their long-term use. These recent studies suggest a new treatment approach to arthritis based on modulation of anti-inflammatory activity of PEMF via adenosine receptors. The advantage of this new approach is the absence of local and systemic side effects.
It is very important that PEMF is capable of stimulating cartilage growth. Age and/or injury related deterioration of cartilage is the major cause of osteoarthritis. The ability of PEMF therapy to regrow cartilage suggests the possibility of positive modification of the underlying condition of osteoarthritis, something that today’s medicine cannot do. PEMF stimulation could be a new effective treatment of the joints that potentially can slow down and even reverse osteoarthritis.
Sotelo-Barroso Fernando et al demonstrated that 3 week of 30 min daily PEMF stimulation can increase cartilage thickness as much as 50 µ. (“Effects of pulsed electromagnetic fields on the cartilage joint thickness of distal femoral metaphysis in the rat”)
Ciombor DM et al demonstrated that deep cartilage lesions are significantly improved by PEMF stimulation. The Ciombor study concluded that PEMF favorably affects cartilage homeostasis by inhibiting it resorption and upregulating expression of major components creating new cartilage. (“Modification of osteoarthritis by pulsed electromagnetic field–a morphological study”)
The first high quality clinical trials of osteoarthritis treatment by PEMF were conducted by Trock et al. (David Trock et al. (“A double-blind trial of the clinical effects of pulsed electromagnetic fields in osteoarthritis”) and (“The effects of pulsed electromagnetic fields in the treatment of osteoarthritis of the knee and cervical spine. Report of randomized, double blind, placebo controlled trials”) These clinical trials demonstrated significant improvements in osteoarthritis of knee and cervical spine.
Effect of PEMF on low back pain was investigated by Lee PB et al. in a clinical trial “Efficacy of pulsed electromagnetic therapy for chronic lower back pain: a randomized, double-blind, placebo-controlled study”. The authors concluded that PEMT treatment reduces pain and disability and appears to be a potentially useful therapeutic tool for the conservative management of chronic lower back pain. For the abstract, refer to Appendix 8.
In Europe, a PEMF device called I-ONE is on the market for several years. It was developed by a group of Italian scientists within the “C.R.E.S. study” (Cartilage Repair and Electromagnetic Stimulation), which has demonstrated the chondroprotective efficacy of PEMF treatment. I-ONE therapy is indicated after joint surgery and in early stages of osteoarthritis and is used for knee and other joints.
BioMagnetic Sciences, LLC developed NOVOPULSE® – a thermally-assisted PEMF therapy- whereby thermal and PEMF stimulations are synergistically combined together in a novel method of pain management and osteoarthritis treatment. The thermal stimulation increases blood flow around the articular cartilage, promotes diffusion of the nutrients to the cartilage and removal of the waste products from the cartilage intercellular space. The waste products from unhealthy or dead cells, many of which are present in the arthritic joints, can be detrimental to the healthy cells. Exposure to proper elevated temperatures cleans the environment and salvages many compromised chondrocytes, which would otherwise die. Heat stimulation increases the viability of chondrocytes and recruits more cells for participation in the PEMF enforced metabolic process, which repairs the cartilage and reduces inflammation -the main source of pain. At elevated temperatures, 39-42oC, the metabolism of chondrocytes and production of proteoglycans and collagen II are significantly higher than that at normal joint temperature. The thermal component enhances the PEMF therapy by augmenting its cartilage repair mechanism and blocks pain thus creating relaxation and comfortable feeling. The thermally- assisted PEMF therapy provides a better, more user-comfortable experiences than other non-thermal or “cold” PEMF.
BioMagnetic Sciences, LLC has developed and offers to the market a new device NOVOPULSE®. NOVOPULSE® is a non-invasive, self-administered, in-home use device. It provides Thermally-Assisted PEMF therapy in 30-minute session for the treatment of lower back pain.
BMS has overcome the technical challenges associated with properly applying PEMF treatments to articular cartilage in general and to the spine in particular. One is the difficulty of creating a sufficiently high electromagnetic field deep inside the body. Another challenge is related to the complicated geometric shape of articular cartilages and its proximity to bones. Electrical resistivity of bones is about 100 times higher than that of cartilage. So, if the electric lines of induced electric field cross not only cartilage but also bone, the electric field locally applied to the cartilage becomes about 100 times lower than that to the bone. That is one reason why adequate coverage of the cartilage with the curl electric field is not achievable with a single coil. NOVOPULSE® employs a proprietary PEMF applicator consisting of multiple coils. The coils, which are strategically positioned around a specific joint, are designed to meet two main requirements: One, an electric field of appropriate magnitude and with the right orientation and distribution must be delivered into the cartilage tissue. Two, the dead zones naturally located around the central axes of single coils must be covered by the electric fields generated by the other coils within the applicator. A wrong orientation of the electric field delivers the therapy into the adjacent bones where its effect on the cartilage is negligent. NOVOPULSE® unique approach eliminates these issues.
• PEMF anti-inflammatory action and biological mechanism are well established.
• PEMF stimulation therapy relieves back pain.
• PEMF stimulation helps increase cartilage thickness in joints.
• Thermal stimulation increases the viability and proteoglycan metabolism of chondrocytes.
• Thermal stimulation increases expression of extracellular matrix genes of proteoglycan core protein and type II collagen in articular cartilages.
• NOVOPULSE® novel technology combines both PEMF and thermal stimulations.
• NOVOPULSE® employs a proprietary technology that delivers the therapy with the proper distribution and orientation to the treatment areas. It applies circumferential electric field in the complete volume of vertebral discs with maximum field at their edges, where it is needed most.
• NOVOPULSE®’ provides thermal stimulation that not only enhances PEMF treatment but also provides deeper and longer pain relief than is achievable with non-thermal, “cold” therapy.
• NOVOPULSE® temperature setting is user defined and computer controlled for maximum comfort.
• NOVOPULSE® promotes both removal of waste from intra-cellular space and diffusion of nutrients into the joints. It improves overall cell metabolism, boosts proliferation and viability of chondrocytes – the major cellular components of cartilage tissue – and salvages significant number of cells.
• NOVOPULSE® provides strong anti-inflammatory action on the low back without the side effects associated with NSAID and other pharmaceutical drugs.
• NOVOPULSE® systems do not require secondary or external thermal sources.
• NOVOPULSE® MKX-1 low back device, generates multiple patterns of electric field, which provide full and complete coverage to both the discs and facet joints.