DEVICES FOR
NON-INVASIVE TRANSCRANIAL ELECTROSTIMULATION OF THE BRAIN ENDORPHINERGIC
SYSTEM: APPLICATION FOR IMPROVEMENT OF HUMAN
PSYCHO-PHYSIOLOGICAL
STATUS
Lebedev V.P.1, Malygin
A.V.1, Kovalevski A.V.1, Rychkova S.V.1, Sisoev
V.N.2, Kropotov S.P.2, Krupitski E.M.3,
Gerasimova L.I.4, Glukhov D.V.5, Kozlowski G.P.6
1Pavlov Institute of Physiology, 2Military
Medical Academy, 3Regional Narcological
Dispensary, Saint-Petersburg; 4Sklifasovsky Research Institute of
Emergency, 5Center of Extreme Medical Situations, Moscow, Russia; 6University
of Texas Southwestern Medical Center, Dallas, TX, USA
SUMMARY
Here, we describe the
clinical application of devices for non-invasive and selective transcranial electrostimulation (TES) of the
antinociceptive system; and, their endorphinergic and serotoninergic
neurotransmitter components. Our data is based on a large number and variety of
experimental and clinical studies. The
process of development and a brief description of these devices are presented.
We also demonstrate the high efficacy of TES treatment for reduction of
psycho-physiological disturbances elicited by stress of different intensities
and a variety of other
factors.
STATE OF THE ART
During the last century,
transcranial electrostimulation (TES) was proposed as a method to elicit electronarcosis
/1/, electrosleep /2/ and electroanalgesia /3/. Many attempts in several countries were
made to introduce these methods into clinical practice /4/. Despite the breathless
expectations based on
TES methodology (i.e., non-pharmacalogic,
easily controlled, with few side effects); the practical results of TES applications were quite negative. In
hindsight, it is understandable because there were: no suitable experimental
models, little knowledge of the optimal parameters for treating specific abnormalities,
or well-controlled studies; that, acceptance of TES into the clinical area was
slow, if at all. Our general aim was to develop the method of non-invasive,
selective activation
of the brain antinociceptive system with its endorphinergic
and serotoninergic mechanisms by means of TES. Some
data were presented previously /5, 6/. The specific
aim of this paper is to describe the process of development of TES devices and its
applications for reduction of psycho-physiological disturbances elicited by
stress of different intensity and some other factors. This study was
accomplished according to the established order of GMP, GLP and GCP.
MATERIALS AND METHODS
Development of devices
In the long history of TES, several different electrical regimens were
introduced rather arbitrarily. To make a choice
Table 1. Characteristics of impulses studied in screening experiments to elucidate of its optimal
parameters for transcranial electroanalgesia
|
Impulse shape |
Frequency (Hz) |
Width (msec) |
|
||
|
Range |
Steps |
Range |
Steps |
||
|
|
40 - 100 |
1 – 5 |
0.1 – 5.0 |
0.05 |
Yes No |
|
100 - 3500 |
10 -50 |
0.1-1.0 |
0.1 |
||
|
|
40 -250 |
10 |
0.1 –5.0 |
0.2 |
No |
of optimal regimen for stimulation of antinociceptive system, broad
screening experiments were performed with non-traumatic pain models in several
species of animals and volunteers with registrations of emotional, motor and autonomic pain-related
events. The shape of impulses, range of frequencies, impulse width and the
steps of its changes are presented in Table 1. All parameters studied were withinin the limits of ones of previously described devices
for electrosleep and electroanalgesia /2, 3/. It was found that optimal
stimulation antinociceptive system to elicit analgesic effect and maximal b-endorphin release are produced by rectangular
impulses only of narrow band parameters of frequency and width slightly different
for different species. The optimal parameters for humans were respectively 77.5
Hz and 3.5-4.0 msec. The relationship between the TES
analgesic and other effects and impulse frequencies was very sharp and had
rather “quasiresonance” shape. For example: ± 2 Hz frequency deviations from resonance point
reduced effects at about 50 %, ± 4 Hz deviations abolished TES effects /6/.
These data gave the basis to exclude an individual adjustment of frequency and
impulse width for concrete patient in devices..
It was also found that constant voltage impulses are
effective in combination with DC in ratio 1:2 only. Contrary constant current impulses
of the equal amplitude had the same efficacy without additional DC. This result gave an opportunity to
reduce significantly the level of current applied. In comparison between the
analgesic efficacy of present TES regimen and regimen described by A.Limoge
A Limits of frequency modulation
Monopolar
Bipolar b |
B 1
|
2
|
3
|
||||||||||||||||||||||||||||||||||
4
|
|||||||||||||||||||||||||||||||||||||
Fig. 1. Output current impulses (A) of TES devices (B).
A. Shape of impulses and limits of frequency
modulation.
B. Different TRANSAIR models. 1- Headset of electrodes.
2- TRANSAIR – 02, the simpliest for outdoor usage, monopolar output impulse, rechargeable battery. 3- TRANSAIR
– 01, for practitioners, mono- and bipolar output impulses, LCD, timer,
frequency control, alarm and protection systems, plug in. 4- TRANSAIR – 04, for
hospitals and outpatients clinics, mono-
and bipolar output impulses with or without frequency modulation, LD
indicators, timer, automatic control, alarm and protection systems, verbal
dialogue with user in process of adjustment
of parameters, plug in.
/7/ it was elucidated that the first one is much more effective. Further improvements of electrical regimen were directed to diminution of local irritating action on the skin under electrodes and increase the TES efficacy in population of patients. To realize the first aim the bipolar impulse with zero net charge (Fig.1A, phase “a” is equal phase “b”) was used. For the second aim the stochastic frequency modulation was introduced in the limits of the width of “quasiresonance” curve at the 50% level of its height (Fig.1,A).
On the basis of these results the development
of some models of devices named later as TRANSAIR (abbreviation - TRANscranial Stimulator for Analgesia,
Immunity and Repair) and adjusted for out-and
indoor usage were developed and manufactured (Fig.1,B).
Experimental studies
The immobilization and
cold stress of different intensity in rats were used as a model estimation of
possible TES antistress effect. The intensity
of stress-related events before and after TES were estimated immunocytochemically in neurons of brain cortex and several brainstem nuclei activation by immediately early gene (C-Fos)
expression /8/ and morphologically by measurement of number and shape of gastric ulcers /9/. TES was performed by
regimen specially adjusted for rats /10/.
Human studies
The blind and placebo-controlled (passive and active placebo) studies were produced to estimate the TES effects on stress-related events, affective disorders, and accompanied psycho-physiological and autonomic disturbances of different intensity in several groups of volunteers and patients. Some subjective verbal and non-verbal tests and objective tests were used for estimation of initial level psycho-physiological status and it changes after TES sessions (Table 2).
Table 2. Groups of volunteers and patients with stress-related events, affective disorders and
accompanied psycho-physiological disturbances and tests its
estimation.
No
|
Groups of volunteers and patients |
Types of stress and fatigue |
n |
Tests and number of indexes (n) |
|
1 |
Workers
|
Everyday stress and fatigue |
141 |
Subjective tests – non-verbal: VAS, Color Lusher’s test
(4). Subjective tests – verbal: Self-estim. test (3), Spilberger’s test (2), Quality of life. Objective tests: Correction test with Landolth’s
rings (8), Critical frequency of flashing merger, Reaction on
moving object, Circulation tests (4), Breathing tests (3), Heart rate variability – two tests (9) |
|
2 |
Soldiers |
Stress and fatigue during the 1st year
of military service |
24 |
|
|
3 |
Servicemen |
Stress and fatigue in real field battle conditions |
65 |
|
|
4 |
Rescue workers |
Professional stress and fatigue |
12 |
|
|
5 |
Relatives of the losts |
Stress – syndrome
of “terrible bereavement” |
67 |
|
|
6 |
Patients |
Fatigue during depression |
18 |
|
|
7 |
Patients |
“Chronic fatigue” syndrome |
27 |
|
|
8 |
Patients |
Stress in postabstinence syndrome |
247 |
|
|
9 |
Patients |
Posttraumatic stress (heavy thermal burns) |
207 |
RESULTS
Experimental studies
It was demonstrated that after even one TES session (30-60 min, current 1.0-1.2 mA) substantially reduced the number of neurons activated after immobilization and marked by C-Fos staining. This effect was found in 9 cortex areas of 12 studied especially in deep cortex layers. The reduction of stress-related C-Fos expression was also observed subcortical structures: in 4 of 6 thalamic nuclei and in 6 of 10 hypothalamic nuclei.
One TES session had
curative and preventive effects on gastric ulcers elicited by immobilization in cold environment
stress. Numbers and severity of ulcers in treated animals were substantially
lower in comparison with
untreated ones. TES effects were naloxone
reversible that support of its endorphinergic nature.
Thus experimental data presented gave the basis for clinical application of TES
antistress effect.
Human studies
All groups of volunteers and
patients included are into Table 2. In the members of the groups 1-4 stress of
different level was elicited by the conditions of professional activity
including groups 3-4, which had some level of danger of death. Members of 5th
group had un-escapable stress as a relatives of lost in mass disaster. Members
of group 6-7 have mainly high level of fatigue. In group 8 patients after treatment alcohol and
heroin withdrawal were included. Patients of group 9 had posttraumatic stress
disorders. In all cases it was demonstrated that
fatigue, stress and other accompanied psycho-physiological disturbances were
significantly improved or abolished after 2-5 TES sessions. The TES effects
were more pronounced in cases of heavier disturbances.
DISCUSSION
It is well known that deficit of endorphins play
important role in stress and affective
disturbances of human psycho-physiological status. TES devices are effective
for activation of the
brain endorphinergic structures and its practical
application is the effective homeostatic
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