![Mechanisms of action of PEMF on the cell. The most accredited current model sees the biochemical pathways activated by the calcium ion (Ca2+) and subsequently by the nitric oxygen (NO) and cGMP as the key mechanisms of the action of PEMFs at the cellular level and, as a consequence, on the responses of tissues. (A) General graphical representation of the model; (B) Schematic detail of the sequence of events starting from the first PEMF pulse with the alignment of the temporal flow diagram of the individual events and the involvement of the various cellular compartments [3,7,8,11].](https://www.researchgate.net/profile/Luigi-Cristiano/publication/346945355/figure/fig1/AS:967517812060160@1607685630077/Mechanisms-of-action-of-PEMF-on-the-cell-The-most-accredited-current-model-sees-the_Q320.jpg)
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J Med Res Surg,
Volume 1 • Issue 6 • 33
Journal of
Medical Research and Surgery
Luigi C, et al., J Med Res Surg 2020, 1:6
Mechanisms of Acon And Eects of Pulsed Electromagnec Fields (PEMF) in Medicine
Crisano Luigi1, Pratellesi Tiziano2
1PresgeLab, Presge Company, Loro Ciuenna (AR), Italy
2BAC Srl, Incisa e Figline Valdarno (FI), Italy
ABSTRACT
Pulsed Electromagnec Field (PEMF) therapy is a non-invasive and non-thermal treatment widely used nowadays
to treat various types of disorders and traumas, both in humans and animals. Inially applied only for wound
healing, today it nds many applicaons in medicine for the treatment of bone fractures, arthris, inammaon,
edema, and pain. Although their mechanisms of acon are sll being studied today, and mainly related to the
calcium signaling pathway, they are eecve in the adjuvant treatment of many human diseases in dierent
medical speciales. This work aims to report the main evidence and research in the medical eld with parcular
reference to the applicaon of PEMF to some medical speciales as regenerave medicine (wound care), sports
medicine, orthopedics, and physiotherapy. Finally, this work also wanted to deepen one of the most recent
applicaons of PEMF in the eld of complex diseases, i.e. in the adjuvant treatment of cancer.
Pulsed electromagnec eld therapy may play an important role in medicine as a complementary treatment for
various human diseases and, by deepening the studies in the future, it will be possible not only to understand
the exact mechanisms of acon but also to extend its applicaon to other pathologies both in the medical and
veterinary elds.
Keywords:
EMF, Pulsed Electromagnec Fields (PEMF), Wound healing,
Regenerave medicine.
Abbreviaons:
CaM: Calmodulin; cNOS: Cytoplasmic Nitric Oxide Synthase;
NO: Nitric Oxide; PEMFs, Pulsed Electromagnec Fields; cGMP:
Cyclic Guanosine Monophosphate.
Introducon
Pulsed electromagnec eld (PEMF) therapy is a type of
electrotherapy that uses pulsed electromagnec elds to treat
an injured area of ssue [1]. The key to the mechanism of
acon of PEMF, and all its biological eects on cells and ssues,
lies precisely in the modulaon of the electromagnec pulse
in a pulsed, rather than the connuous manner, as in classic
magnetotherapy, from which it is completely dierent. PEMF is
not part of magnetotherapy technologies.
The device that delivers PEMFs consists of a micro-generator
and an antenna. The laer is the eector part of the device, i.e.
the acve part that emits PEMFs with a typical carrier frequency
of 27.12 MHz [2]. PEMF waveforms have been designed to
penetrate completely through all types of ssues, from the skin
to bone, and represent a non-invasive and non-thermal type
of treatment [3]. Therefore, since their mechanism of acon
resides exclusively in non-thermal eects, they can be used
in medicine as a complementary treatment of many types of
pathologies, included traumas or disorders related to sports
medicine and physiotherapy, and any type of acute inammaon
or injury characterized by a high inammatory component.
Generally, treatment mes range from 20 minutes to 8 hours
a day, depending on the nature of injury and characteriscs of
the device [4], but PEMFs can be kept acve even in cycles of
twenty-four hours unl the aenuaon and/or disappearance of
the cardinal signs and symptoms of inammaon [5], including
pain, the aenuaon of which starts from the delivery of the
rst impulse by the device.
PEMF has been applied and studied for over twenty years
as a non-invasive technology for the promoon and speed of
wound healing and is eecvely used as an adjuvant treatment
in various pathologies including bone fractures, arthris,
osteoarthris, acute inammaon, chronic inammaon,
edema, pain, chronic pains, wounds, and chronic wounds [1,6-
10]. In the last ten years, their mechanisms of acon have been
deepened and, although they are sll the subject of study
today, some biochemical and metabolic pathways have been
highlighted that are acvated as a result of their interacon with
living ssues and that explain the therapeuc eects detected
in vivo, as well as in vitro.
Mechanism of acon
The mechanisms of acon of PEMF can be divided into three
types, i.e. physical mechanisms, biophysical mechanisms, and
purely biological mechanisms. While the physical mechanism of
acon is relavely simple, well known, and related to Faraday’s
law of inducon, which states how “a me-varying (pulsang)
electromagnec eld induces an electric eld in a nearby
conductor” [1], the mechanisms of acon biophysical and
biological are indeed very complex.
With every single pulse, the target ssue is hit by an
Mini Review
Correspondence to: Luigi Crisano, PresgeLab Presge, Loro Ciuenna, Italy; Email: presge.infomed@gmail.com
Received date: November 18, 2020; Accepted date: December 03, 2020; Published date: December 10, 2020
Citaon: Luigi C, Tiziano P (2020) Mechanisms of Acon And Eects of Pulsed Electromagnec Fields (PEMF) in Medicine. J Med Res Surg 1(6): pp. 1-4.
Copyright: ©2020 Luigi C, et al. This is an open-access arcle distributed under the terms of the Creave Commons Aribuon License, which permits unrestricted
use, distribuon and reproducon in any medium, provided the original author and source are credited.
Authors contribuon: The authors contributed equally to the wring of this work.
Page 1 of 4
J Med Res Surg,
Volume 1 • Issue 6 • 33
Citaon: Luigi C, Tiziano P (2020) Mechanisms of Acon And Eects of Pulsed Electromagnec Fields (PEMF) in Medicine. J Med Res Surg 1(6): pp. 1-4.
Page 2 of 4
electromagnec eld.
The main eect of this smulaon happens at the level
of the plasma membrane of the cells, which undergoes a
transient depolarizaon [7]. This event triggers very important
secondary eects (a biophysical mechanism) through the
transient opening of specic transmembrane ion channels,
among which the voltage-dependent channels for the Calcium
ion (Ca2+) stand out. Calcium is an important second cellular
messenger, in fact, the entry of calcium into the cell, and its
binding at the cytoplasmic level with Calmodulin (CaM), in a
me equal to milliseconds from a single pulse, triggers a whole
set of biochemical pathways to cascade in the cytoplasm. They
include various enzymac acvaons among which the release
of Nitric Oxide (NO), in a me equal to seconds from a single
pulse, through the acvaon of the cytoplasmic nitric oxide
synthase (cNOS) [1,3,7,11,12].
Nitric oxide, considered a soluble hormone, in turn, acvates
a whole set of biochemical pathways, one of which leads to
the producon of Cyclic Guanosine Monophosphate (cGMP),
another second messenger, in a me equal to seconds/
minutes from a single pulse. From this moment the terary
eects of PEMF begin, of a purely biological type, which
connue over a period ranging from a few hours to days and
weeks starng from the rst impulse and which include the
transcriponal acvaon of various genes into the cell nucleus
with the producon of growth factors and other proteins and
transmembrane receptors that will result in the orientaon
of the cells, regardless of the ssue they are part of, to
regeneraon and restore homeostasis [1,3,8,11-13] (Figure 1).
Figure 1: Mechanisms of acon of PEMF on the cell. The most accredited current model sees the biochemical pathways acvated by the calcium ion (Ca2+) and
subsequently by the nitric oxygen (NO) and cGMP as the key mechanisms of the acon of PEMFs at the cellular level and, as a consequence, on the responses of
ssues. (A) General graphical representaon of the model; (B) Schemac detail of the sequence of events starng from the rst PEMF pulse with the alignment
of the temporal ow diagram of the individual events and the involvement of the various cellular compartments [3,7,8,11].
What is observed macroscopically is the reducon of
inammaon, pain, edema, and complete ssue regeneraon,
including neovascularizaon and remodeling of the extracellular
matrix up to complete restoraon of the injured ssue [2,5]. All
the cells involved in an injury respond to the acon of PEMF,
including endothelial cells (which will rebuild the injured
blood vessels), broblasts (which will proliferate and repair
the injured extracellular matrix), muscle cells, chondrocytes,
and osteoblasts (which will undergo a more rapid and ecient
proliferaon) [12].
The acvity of the cells of the immune system, in parcular
the inammatory component, is instead sedated (lowering of
the levels of interleukins) [5] and the acvaon of monocytes
to macrophages is favored to clean the injured area from
microorganisms, foreign bodies, and dead cells. Ulmately,
of the possible outcomes of acute inammaon, i.e. necrosis,
chronic inammaon, and healing, PEMF blocks the rst two
and favors the regenerave outcomes of cells and ssues.
Applicaon elds
The PEMF, as previously menoned, promotes ssue healing
and nd applicaon in various elds of medicine to promote
healing following various kinds of traumas, injuries, post-surgical
wounds, and inammaons. Pathologies that nd the eecve
applicaon of this technology include bone fractures, arthris,
osteoarthris, acute and chronic inammaon, edema, pain,
chronic pain, wounds, and chronic wounds [3,7,10,12]. PEMFs
are also applied in physiotherapy, orthopedics, osteopathy,
rehabilitaon pracce, sports medicine, and tness, including
the neuromuscular recovery of the post-workout athlete. The
pathologies and disorders that may be included, in addion to
those already listed above, concern all injuries, traumas, and
inammaons aecng the shoulder, elbow, hand, knee, spine,
hip joint, ankle joint, and foot [4,11,12,14]. Also included may
be all pains of an arthric nature, pain at the level of tendon
inserons (e.g. tennis arm, golfer’s elbow, pitcher’s shoulder,
and scapulohumeral periarthris), overload syndrome,
J Med Res Surg,
Volume 1 • Issue 6 • 33
Page 3 of 4
Treatment of tendinis
PEMF can reduce pain and increase mobility right from the
rst applicaons even in paents who suer from the disorder
and do not respond or cannot take corcosteroid-based drug
therapy [7,10,12].
Adjuvant treatment of cancer
Very recent studies concern the possible applicaon of
PEMF as an adjuvant in the non-surgical treatment of tumor
pathologies, in parcular solid tumors [22,23]. Research and
evaluaons are underway both in vitro and in vivo on animal
models and in the clinic on case studies. The rst results
seem very encouraging as there is a decrease in the vitality
of cancer cells, a reducon/delay in tumor angiogenesis, and
a decrease in the growth rates of cancer cells. PEMF also
promotes apoptosis and/or necrosis of tumor cells [10,24-26].
The biochemical mechanisms underlying what is observed are
not yet clear but it is assumed that PEMF, while in a normal cell
induces it to homeostasis, in a tumor cell probably reacvates
metabolic and signaling pathways bypassed or silenced by
the neoplasc transformaon process such that the cell is so
directed towards apoptosis or necrosis.
In clinical applicaons, it has been seen that there are specic
frequencies (tumor-specic frequencies) that have eects
on cancer cells [27] while some frequencies do not aect
metastases or tumor cells but only on the healing of lesions,
in parcular in the post-surgical aer exeresis of a solid
tumor with beer and faster wound healing, the reducon of
recovery mes and eliminaon of infecons and post-surgical
scar formaon [28,29]. Despite the posive results of the rst
studies, the applicaon of PEMF in the oncology eld is sll
under study and requires further invesgaon.
Conclusions
PEMFs can penetrate completely through all types of ssues,
from the skin to bone, and are capable of inducing cellular and
ssue responses, including transcriponal acvaon. PEMFs
are cheap, very simple to use, non-invasive, non-thermal,
have no known side eects, and can play an important role
in the complementary treatment of various human diseases
or trauma, included bone fractures, arthris, osteoarthris,
acute inammaon, chronic inammaon, edema, pain,
chronic pains, wounds, and chronic wounds. Although the
mechanisms of acon of PEMFs have yet to be fully elucidated,
they nd interesng applicaons in medicine and various
medical speciales, including sports medicine, orthopedics,
and physiotherapy, and currently, it is under study their
applicaon, and their possible benets, in complex and
chronic-degenerave diseases, including cancer.
In conclusion, PEMFs may play an important role in medicine
as a complementary treatment for various human diseases
and further studies will clarify their mechanisms of acon and
extend their applicaon elds both in human and veterinary
pathology.
Acknowledgment
Thanks to Mr. Simone Pratellesi and Mr. Valerio Pratellesi for
all the technical assistance, informaon, and material provided,
including many scienc studies and preliminary data, which
patellar pathology, meniscal pathology, degeneraon of the
intervertebral discs and vertebral joints, “witch stroke”, cervical
spine pain due to “whiplash”, ischial pain, muscle contractures,
and post-traumac outcomes. All degenerave pains, painful
tendon inserons, bursis, Achilles tendon inammaon,
calcaneal spine, and at foot pain also may benet [10,12,15].
Recent studies also regard their applicaon as an adjuvant
treatment for complex diseases such as cardiovascular
diseases, diabetes, neurological disorders, microbial infecons,
and tumors [1,10,11]. PEMFs have no known side eects [3].
Wound healing
PEMF has its main and historical applicaon in the treatment of
wounds. Wound healing is a complex process involving cascades
of inammatory, proliferave, immune, and ssue remodeling
reacons [16]. Clinical studies have shown that treatment with
PEMF can promote and accelerate the healing of both fresh
and recent wounds, including post-operave wounds, as well
as chronic wounds such as pressure sores and diabec leg and
foot ulcers. The mechanism underlying this ability appears to
be partly due to the increased vascularizaon induced in the
ssue by smulaon via PEMF, but also to the beer perfusion
of the injured ssue and the beer oxygenaon, all important
factors for wound repair [1,11,16,17].
PEMF smulates endothelial cells to reproduce and rebuild
injured blood vessels, increasing angiogenesis over me in the
ssues aected by the wound [1,18]. PEMF also smulates
broblasts to rebuild the injured extracellular matrix, smulates
epithelial cells to reproduce, and restore lost ssue connuity.
A key and very interesng aspect are that smulaon using
PEMF synchronizes the reproducon acvity of the cells
invested by the electromagnec eld in a way that no cell
species can privilege the others. This parcular mechanism
is sll under study but the eects are visible as the healing
of fresh wounds occurs when treated with PEMF, mainly
by the rst intenon, or similar to the rst intenon, rather
than by the second intenon. This means that there is less
development of keloids and disguring scars [3]. Also, PEMFs
reduce inammaon and pain from the rst impulse. This is
signicant in the management of all wounds but especially
post-operave wounds [1].
Bone repair
Bone repair requires the cooperaon of specic bone cell
types: osteoblasts and osteoclasts. PEMFs have been shown to
aect bone repair through several mechanisms including the
smulaon of brocarlage calcicaon in the space between
bone segments, the increased blood ow and wound healing as
a result of eects on calcium ion channels, and increased bone
formaon rate by osteoblasts (1,4,7,10,19,20]. On the contrary,
it is found that osteoclasc acvity is reduced. Furthermore,
the use of PEMF as a treatment for unconsolidated fractures
has proven to be very eecve [4].
Treatment of osteoarthris, arthris, and osteoarthris
PEMF smulaon has been shown to have clinical ecacy for
the treatment of arthrosis and arthris, including osteoarthris
and rheumatoid arthris [1,7,9,10,12,21]. PEMF suppresses
the inammatory response [5] and is an adjunct in the
management and treatment of pain.
Citaon: Luigi C, Tiziano P (2020) Mechanisms of Acon And Eects of Pulsed Electromagnec Fields (PEMF) in Medicine. J Med Res Surg 1(6): pp. 1-4.
J Med Res Surg,
Volume 1 • Issue 6 • 33
Page 4 of 4
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have been used as a reference and idea to deepen and expand
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Funding
This research did not receive any specic grant from any
funding agency in the public, commercial or not-for-prot
sector.
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