Noninvasive Selective Transcranial Electrostimulation1
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Transcript of Noninvasive Selective Transcranial Electrostimulation1
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NONINVASIVE SELECTIVE TRANSCRANIAL ELECTROSTIMULATION
OF THE BRAIN ENDORPHINERGIC STRUCTURES (TES-THERAPY)
AS AN EFFECTIVE TOOL OF REVITALIZATIONE MEDICINE
Professor Lebedev V.P., MD, PhD, Dr. of Sci
Center of Transcranial Electrostimulation, Pavlov Institute of Physiology,
Russian Academy of Sciences, St.- Petersburg, Russia
e-mail:[email protected]; www.tes.spb.ru
Endorphins are known to have many properties that allow considering them homeostatic
regulators, which is manifested during their systemic and intracerebral injections. It has been
shown that they have a pronounced anti-nociceptive effect, are anti-stressor hormones, help
improve memory, activate immune system, promote elimination of age-related alterations of
vascular walls, prevent aging by removing peroxide compounds. It is an appearing complex of
such effects, which is important for use in revitalization medicine.
Endorphins are produced predominantly by brain nerve cells and, to a lesser degree, by
adrenal medullary cells and neurons of intestinal plexuses. Subcortical brain structures
containing endorphinergic and closely related serotoninergic neurons are combined by the
common term protective brain mechanisms as their direct electrostimulation produced the
above homeostatic effects.
This work presents data on development of the transcranial (through the skull)
electrostimulation (TES) for noninvasive selective activation of protective (anti-nociceptive)
mechanisms of brain subcortical mechanisms, which allows using activation of the brain
protective mechanisms as an efficient tool of revitalization medicine.
I. Development of the method of TES-therapy
The present procedure and its application in clinical practice, unlike the earlier describedmethods of transcranial electrostimulation (electroanesthesia, electrosleep, electroanalgesia) was
carried out with use of rules of GLP (good laboratory practice) and GCP (good clinical practice)
accepted in international practice. In compliance with these rules, to study mechanisms of the
effects, it seemed necessary to use the most current methods of study of mechanisms, screening
to reveal optimal regime of action, use of experimental-pathological models in preclinical studies
and double blind control in clinical observations.
Taking into account these rules, we formulated tasks of the investigation and directed ways
of their solution, presented in Table 1. This table also presents principal results of solution of
these tasks.
mailto:[email protected]:[email protected]:[email protected] -
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Table 1
Setting of tasks and ways of their solution in the course of development of the TES method
Task Way of solution Result
Finding of optimal
position of electrodes on
the head surface for
approaching current to
structures of brain
protective mechanisms
Determination of ways of current
in the brain by nuclear magnetic
resonance tomography
Activation of protective brain
mechanisms can be performed
only if the current runs in
sagittal direction (fronto-
retromastoidal position of
electrodes)
Selection of optimal
electric TES parameters
Screening on experimental models
(pain, reflexes, wounds, tumors,
etc.)
Quasi-resonance regularities
frequencyeffect and
durationeffect have been
revealed to serve the ground for
construction of therapeutic TES
apparatuses
Proofs of activation of
endorphinergic and
serotoninergic structures
of protective brain
mechanisms
1. Mapping of activated neurons
by immunocytochemical and
autoradiographic methods.
2. Determination of levels of -
endorphin in the brain,
cerebrospinal fluid and blood
plasma by radiochemical and of
serotonin in the cerebrospinal
fluid and blood plasma by
biochemical methods.
3. Use of agonists and antagonists
of opioid and serotoninergic
receptors
The selected TES regimes have
been proved to activate
selectively endorphinergic and
serotoninergic structures of
protective brain mechanisms
Using a modified NMR-tomography, it was shown that only the sagittally directed current
(the foreheadmastoids position of electrodes) could reach the anti-nociceptive system by
running through two intracranial ways (cerebrospinal fluid of basal cisterns and brain ventricles).
In screening experiments there were revealed quasi-resonance correlations frequency of
impulseseffect and duration of impulseseffect of activation of the anti-nociceptive
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system. These correlations were further used to design equipment realizing the method of TES-
therapy (Fig. 1, A).
By the above type of the brain electrostimulation, indeed, the anti-nociceptive system
structures were activated. Thus, incorporation of [3H]-deoxyglucose (autoradiography) indicating
activation of neurons increased in the periaqueductal gray substance and decreased in the
brainstem relay nuclei involved in transmission of ascending nociceptive impulsation as well as
in somatosensory brain cortex.
The elaborated TES-regime activated predominantly endorphinergic and serotoninergic
mechanisms of the anti-nociceptive system. There also was observed an essential rise of -
endorphin concentration in brainstem structures, spinal cord dorsal horns, cerebrospinal fluid and
blood as well as of metenkephalin in the cerebrospinal fluid (radioimmunochemical studies).
Fig. 1. Dependence of TES-effects (A, analgesia) and of blood -endorphin level (B) on
frequency of transcranial electrostimulation
Maximal increase of-endorphin concentration was observed during actions with parameters
coinciding with point of TES quasi-resonance (Fig. 1, B). The level of serotonin (5-HT) in the
cerebrospinal fluid also increased. In parallel with the increase of the opioid peptide
B
C1 C2 60 65 70 75 80 Hz
pM/L
30
20
10
0
-en
dorphi
n
A
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concentration in the cerebrospinal fluid there occurred a decrease of the P substance level,
especially on the background of a nociceptive stimulation.
The TES effects were eliminated by an antagonist of opioid receptors, naloxon, and by
antagonists of serotonin receptors, 5,7-dihydrotryptamine and mergolin, and were absent on the
background of morphine tolerance. Potentiation of the TES effects was produced by
enkephalinase inhibitors (D-leucine, D-phenylalanine), 5-HT precursors, inhibitors of
monoamine oxidase and tryptophan pyrrolase (a decrease of leakage of the 5-HT precursors by
the kinurenin pathway). Changes of the TES effects under action of cholinergic and GABA-ergic
agonists-antagonists were poorly expressed.
The presented data demonstrate essential differences in substantiation of the present
development of the TES method from the earlier offered kinds of transcranial actions
(electroanesthesia, electrosleep, and electroanalgesia), of which development was based on asubjectively justified wish to get a clinically important effect without medications; however,
unfortunately, their development was not substantiated by experimental methods. On the basis of
this results several models of devices for transcranial electrostimulation (TES-therapy) were
developed (Fig.2)
Fig. 2. Models of Transair for hospital, outpatient clinic and domestic usage, and position
of electrodes on the head.
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II. The main effects of the TES-therapy general characteristics
Fig. 3 presents the main types of the TES effects considered in detail by collections of papers
published by the TES Centers [1, 2]. All these effects have been proved to be due the central or
peripheral action of endorphins. It is to be emphasized that the scheme (Fig. 3) merely
demonstrates our analytical approach to the TES effects, but does not fully characterize their
clinical peculiarities.
In reality the therapeutic TES effects have the following most important peculiarities:
have a h omeo s ta t i c character their normalizing action is manifested only for disturbed
functions;
are manifested only as a co mp le x during treatment of the main pathology, positive
actions are observed on manifestations of accompanying disturbances (for instance, analgesiais accompanied by stimulation of reparation);
Fig. 3. The main effects of the TES therapy
Normalizationof autonomic and hormonal regulation
Improvement of the psychophysiological statusand quality of life
Analgesia
Vasomotorregulation
Antiaddicteffects
Activationof tissue repair
Stimulationof immunity
Inhibitionof tumor growth
TES
Brain
-endorphin
Blood
-endorphin
Central effects Peripheral effects
effects
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are manifested s ys t emic a l l y on one hand, during treatment of different pathologies
with similar syndromes (for instance, pain or depression), on the other hand, during treatment
of different disorders produced by the same factor or of different pathologies connected with
disturbances of the single functional system.
III. TES-therapy in revitalization medicine
According to the current concepts put forward by Academician A.N. Razumov, the main
contents of the revitalization medicine are preservation and restoration of health of healthy and
practically healthy people as well as of the people who have functional disturbances or
premorbid disorders, medical rehabilitation of patients and disabled people. In our opinion, the
revitalization medicine is to include a new important part r eg e ne r a t io n me d i c in e .
. TES-therapy for preservation and rehabilitation of health of healthy and practically
healthy people.
From the determination of the revitalization medicine according to Acad. A.N. Razumov, it
follows that one of its basic scientific platforms is the theory of stress and adaptation.
Our investigations carried out with use of psychophysiological methods (Table 2) have
shown that TES-therapy has a pronounced normalizing and anti-stressor effects in disorders of
the psychophysiological status of various degrees of severity.
Table 2
Methods of evaluation of psychophysiological effects of TES-therapy
Subjective tests Objective tests
Non-verbal
- Visual analogue scale
- Lushers visual test
Verbal
- (??) test
- Spielberger (?) test
- Life quality test
- Correction test with Landolts rings
- Critical frequency of fusion of flashings
- Response to moving object
- Cardiovascular tests
- Respiratory tests
- Variational pulsometry
Table 3 indicates the main cases of application of TES-therapy for elimination of fatigue,
tiredness, stress, and stressor disorders. Efficiency of TES-therapy during fatigue has been
confirmed by blind control studies with use of active and passive placebo. These effects are
beyond any doubt to be due to the endorphinergic mechanism of TES-therapy.
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Table 3
Normalizing effects of TES-therapy during psychophysiological disturbances of various nature
Groups of observationsDirections of the normalizing action of TES-
therapy
Practically healthy people after a routine
work Elimination of fatigue
Rescuers after work Elimination of fatigue
Recruit soldiers and military students Military professional adaptation
Highly specialized military staff Preparation to fighting use and recovery after it
Relatives of victims lost in massive
catastrophesElimination of the syndrome of loss
Patients with syndrome of chronic fatigue Elimination of syndrome of chronic fatigue
Wounded people, refuges Treatment of posttraumatic stressor disorders
Table 3 summarizes cases of efficient TES application which are arranged according to an
increase of the degree of severity of stress and of disorders of the psychophysiological status. It
is seen that TES-therapy can be used both in everyday life at a routine work and in a stressed
work possibly connected with a danger (divers). TES-therapy has turned out to be efficient in
chronic stress at deadaptation at military service initial stages as well as under conditions of real
fighting actions and in wounded people.
B.TES-therapy for elimination of premorbid disorders and for rehabilitation.
Elimination of premorbid disorders and rehabilitation are the most important tasks of
revitalization medicine; their solution is in a close contact with medicine of labor. Efficiency of
use of TES therapy to solve these tasks can be demonstrated by the example of a number of
examples.
1. TES-therapy promotes statistically significantly normalization of arterial pressure (AP) at
arterial hypertension of I degree (APsyst = 140-159 mm Hg) and hypotension. There are certain
perspectives of use of TES-therapy for prevention of development of hypertension at
prehypertension (APsyst = 130-139 mm Hg). This state has recently been identified in the 7-th
report (2004) of the USA United National Committee on detection, evaluation, and treatment of
high AP, as risk of cardiovascular complications, according to data of the Framingham study,
increases twice. Our experimental studies have shown that normalization of AP is based on
endorphin action on vasomotor center.
2. TES-therapy is highly efficient for elimination of disturbances of the psychophysiological
status in women at various stages of their life. We mean elimination of typical complication of
the first half of pregnancy (especially vomiting) and manifestation of climacteric disorders
(vegetovascular dystonia, depression).
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3. Extensive experimental-clinical studies have shown TES-therapy to be highly efficient
during elimination of pain syndromes of various geneses and various localizations (Table 4). The
latter is accounted for by that endorphins, apart from their analgesic action, also have an anti-
inflammatory effect.
4. TES-therapy has been used successfully for rehabilitation of chronic alcoholics and opium
drug abusers for elimination and for elimination of postabstinence affective disorders, which
eventually leads to a decrease or elimination of pathological thrive for repeated use of alcohol
and narcotics.
Table 4.
Types of nociceptive syndromes cupped up with use of TES-therapy
Spondylogenic pains
Pains connected with lesion of nerves
neurites,
neurinomas,
phantom pains
Headaches
pains of tension, arachnoiditis,
postcommotion syndrome,
migraine
Orofacial pains
trigeminitis, glossalgia
Fibromyalgia
Pains at deforming arthroses
Pains at endometriosis
Postoperational and posttraumatic pains
Oncological pains
The presented examples show that use of TES-therapy is an efficient tool of rehabilitative action.
It is important to be emphasized that this instrument is applicable under conditions of the usual
life of the working-capacity population.
. TES therapy in revitalization medicine
A new direction, revitalization medicine, has recently been formed. The revitalization medicine
is determined as a possibility of replacing aging/damaged cells by genetically similar young and
functioning cells. This can be achieved by use of embryonic stem cells of human cloned embryos
or pluripotent stem cells of adults (Kahn A., 2001). TES-therapy does not use stem cells, but
owing to activation of the endorphinergic system and released endorphins it can stimulate
considerably processes of reparative regeneration. From this, it follows that use of TES-therapy
is a new direction of revitalization medicine.
Table 5
Examples of stimulating effects of TES-therapy on processes of regeneration
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term=%22Kahn+A%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term=%22Kahn+A%22%5BAuthor%5D -
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Types of tissues Experimental models Therapeutic application
Skin epithelium and
connective tissueSkin wounds Burns, wounds, trophic ulcers
GIT epithelium and
connective tissue
Stressor and toxic gastric
ulcers
Ulcerative disease of stomach and
duodenum
Hepatocytes Toxic and mechanical injuries Hepatoses, hepatitides, alcoholcirrhosis
cells of Langerhansislands
Toxic injuriesType 2 diabetes mellitus, metabolic
syndrome
Nerve fibers Section of nerves Neurosensory hypoacusis
Connective tissue Legation of the descending
branch of coronary artery
Acute myocardial infarct
Our obtained experimental-clinical data are presented in Table 5. Apart from use of TES-
therapy under conditions of hospitals, a part of such therapeutic effects can be for rehabilitation
and maintenance of a state after medication therapy as well as for prevention.
One of examples is an efficient use of TES-therapy for stimulation of regeneration of gastric
mucosa in ulcerative disease and prevention of spring-autumn exacerbations. This reparative
effect is combined with analgesia and normalization of life quality parameters. Another
important example is a pronounced improvement of hearing in sensoneural hypoacusis under
effect of TES-therapy. Remarkably, this effect is also found in people suffering from
professional sensoneural hypoacusis caused by a long work under conditions of intensive noise
(for instance, in helicopter workers or in workers of atomic ship building).
IV. Conclusion
The presented data have shown that TES-therapy can be an important component of the set
of actions of revitalization medicine by promoting maintenance and recovery of the health of
healthy and practically healthy people suffering from functional disturbances or premorbid
disorders as well as of medical rehabilitation of patients and invalids. It is to be particularly
emphasized that TES- therapy has the ability to activate reparative regeneration. An important
peculiarity of TES-therapy is that this non-medication method of treatment has a rather limited
circle of contraindications, with practically no side effects. From economical point of view this
method of revitalization medicine is highly profitable, as the TRANSAIR apparatuses realizing it
are simple and convenient for use.
V. References1. Transcranial Electrostimulation. Experimental-clinical investigations. Ed. by V.P.
Lebedev, St.-Petersburg, 2001, Vol. 1, 528 pp.
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2. Transcranial Electrostimulation. Experimental-clinical investigations. Ed. by V.P.
Lebedev, St.-Petersburg, 2003, Vol. 2, 524 pp.
3. Transcranial Electrostimulation. Experimental-clinical investigations. Ed. by V.P.
Lebedev, St.-Petersburg, 2009, Vol. 3, 392 pp.