Neuromuscular electrostimulation techniques: historical aspects and

Clinical Nephrology, Vol. 78 – No. Suppl. 1/2012 (S12-S23)
Neuromuscular electrostimulation techniques:
historical aspects and current possibilities in
treatment of pain and muscle waisting
Original
©2012 Dustri-Verlag Dr. K. Feistle
ISSN 0301-0430
DOI 10.5414/CNX77S106
e-pub: ■■month, ■■day, ■■year
Key words
electric ray fish –
franklinism – galvanism
– faradism – transcutaneous electrical nerve
stimulation – percutaneous electrical nerve
stimulation – spinal cord
stimulation – high tone
external muscle
stimulation – electrical
myostimulation
Received
■■■;
accepted in revised form
■■■
Correspondence to
August Heidland, MD
Department of Internal
Medicine, University of
Würzburg and KfH
Kidney Center,
Hans-Brandmann-Weg
1, 97080 Würzburg,
Germany
august.heidland@​
t-online
August Heidland1,2, Gholamreza Fazeli3, André Klassen2, Katarina Sebekova4,
Hans Hennemann5, Udo Bahner2 and Biagio Di Iorio6
of Internal Medicine, University of Würzburg, 2KfH-Kidney Center,
of Pharmacology and Toxicology, University of Würzburg, Würzburg,
Germany, 4Institute of Molecular Biomedicine, Medical Faculty,
Comenius University, Bratislava, Slovakia, 5KfH Kidney Center Coburg, Coburg,
Germany, and 6Faculty of Medicine and Surgery, Seconda Universita di Napoli, Italy
1Department
3Institute
Abstract. Application of electricity for
pain treatment dates back to thousands of
years BC. The Ancient Egyptians and later
the Greeks and Romans recognized that
electrical fishes are capable of generating
electric shocks for relief of pain. In the 18th
and 19th centuries these natural producers of
electricity were replaced by man-made electrical devices. This happened in following
phases. The first was the application of static electrical currents (called Franklinism),
which was produced by a friction generator.
Christian Kratzenstein was the first to apply
it medically, followed shortly by Benjamin
Franklin. The second phase was Galvanism.
This method applied a direct electrical current to the skin by chemical means, applied
a direct and pulsed electrical current to the
skin. In the third phase the electrical current
was induced intermittently and in alternate
directions (called Faradism). The fourth
stage was the use of high frequency currents
(called d’Arsonvalisation). The 19th century
was the “golden age” of electrotherapy. It
was used for countless dental, neurological,
psychiatric and gynecological disturbances.
However, at beginning of the 20th century
electrotherapy fell from grace. It was dismissed as lacking a scientific basis and being used also by quacks and charlatans for
unserious aims. Furthermore, the development of effective analgesic drugs decreased
the interest in electricity. In the second half
of the 20th century electrotherapy underwent
a revival. Based on animal experiments and
clinical investigations, its neurophysiological mechanisms were elucidated in more
details. The pain relieving action of electricity was explained in particular by two main
mechanisms: first, segmental inhibition of
pain signals to the brain in the dorsal horn
of the spinal cord and second, activation of
the descending inhibitory pathway with en-
hanced release of endogenous opioids and
other neurochemical compounds (serotonin,
noradrenaline, gamma aminobutyric acid
(GABA), acetylcholine and adenosine).
The modern electrotherapy of neuromusculo-skeletal pain is based in particular
on the following types: transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS or
electro-acupuncture) and spinal cord stimulation (SCS). In mild to moderate pain, TENS
and PENS are effective methods, whereas
SCS is very useful for therapy of refractory
neuropathic or ischemic pain. In 2005, high
tone external muscle stimulation (HTEMS)
was introduced. In diabetic peripheral neuropathy, its analgesic action was more pronounced than TENS application. HTEMS
appeared also to have value in the therapy
of symptomatic peripheral neuropathy in
end-stage renal disease (ESRD). Besides its
pain-relieving effect, electrical stimulation is
of major importance for prevention or treatment of muscle dysfunction and sarcopenia.
In controlled clinical studies electrical myostimulation (EMS) has been shown to be
effective against the sarcopenia of patients
with chronic congestive heart disease, diabetes, chronic obstructive pulmonary disease
and ESRD.
Introduction
Pain is a constant companion from
birth to death in our everyday life [1]. Its
prevalence in patients with end-stage renal disease (ESRD) is much higher than in
the general population. In the majority of
these individuals management of pain is
inadequate [2, 3]. This is in particular due
Neuromuscular electrostimulation techniques: historical aspects and effects
S13
similar manner Hippocrates (420 BC) used
the numbing action of the electrical ray fish
(black torpedo fish). The Roman physician
Scribonius Largus (AD 47) (Figure 1) was
the first who, in the Compositiones Medicae,
prescribed the direct contact with the ray fish
for pain relief in patients with gout, arthritis
or headaches [6]. The torpedo fish generates
discharges from as little as 8 volts up to 220
volts, depending on the species. The average
current is ~50 volts.
Figure 1. Artist’s impression of use of the electrical torpedo fish in the treatment of gout (a) and
headache (b). Reproduced with permission from
Perdikis 1977, South Africa Journal of Surgery [7].
to enhanced adverse side effects of many
analgesic agents (owing to their altered
pharmacokinetics and pharmacodynamics in renal failure) and saturation of the
patients due to daily tablet overload. Consequently, non-pharmacological strategies
such as electrotherapy could be a useful alternative. It is the goal of this paper to convey a better understanding of the potential
clinical applications of electrotherapy in its
different forms. Their non-invasive kinds
are fortunately without relevant side effects
– a good reason for its broader application.
Historical aspects of electrotherapy
Application of electricity for pain relief
dates back to antiquity. It is assumed that
as early as 9000 BC magnetite and amber
(“animated minerals”) were used by Ancient
Egyptians for treatment of headaches and
arthritis [4]. Also some hints assumes that
in the time of Pharaohs the Egyptians were
even able to produce electricity from a direct
current battery (Ureus battery) [5].
A very effective approach was the contact with electrical fishes. There are hints
that the Ancient Egyptians employed the
Nile catfish for treatment of severe painful
conditions. Their power has been shown in
tomb paintings as early as 2750 BC [6]. In a
In the 18th – 19th centuries, pain treatment by natural electricity was replaced by
man-made electricity with invention of electrical devices. According to Turrell [8] the
following four phases of electrotherapy have
to be mentioned: the first phase was the application of static or atmospheric electricity,
called Franklinism. It was characterized by
high voltage and low milliampere currents,
which were derived from a frictional machine
which induced sudden shocks and sparks. The
method dates back to the German engineer
Otto von Guericke who developed frictional
electricity by an electrostatic sulphur sphere
in 1672 [9]. Later, the storage of the electrical charge (Figure 2) was made possible by
invention of the Leiden jar (the forerunner of
the electrical capacitor). The first medical use
of static electricity in Europe was performed
in 1744 by the German physician Christian
Kratzenstein. A few years later (1752), the
American scientist and politician, Benjamin
Franklin, invented the “Magic Square”, a
simple form of a condenser capable of giving strong shocks for treatment of various
illnesses [10]. Another approach was the use
of a large-sized static-induction machine, the
“improved Holtz”, which worked with high
power under any weather conditions. In contrast the old-fashioned friction machines did
not work in stormy weather or when the atmosphere was damp or humid [11].
The second phase was Galvanic current (around 1800s), which allowed the direct contact of dynamic electricity over the
nerves without shocks and sparks. Introduction of “contact electricity” was preceded by
the discovery of Galvani (1780) showing that
the severed legs of a dead frog kicked outward when stimulated by electrical currents.
Galvani’s assumption of “animal electricity” was criticized by Alessandro Volta. He
could demonstrate that the electricity leading
Heidland, Fazeli, Klassen et al.
S14
Figure 2. Otto von Guericke’s demonstration of
the first electrical machine using friction [9].
to contraction of the frog muscle was not of
animal source but of electrochemical origin
[10]. Subsequently in 1800, Volta showed that
when two dissimilar metals and brine-soaked
cloth are placed in a circuit, an electric current
could be produced. This discovery resulted in
the invention of the voltaic pile – the first form
of a battery. Galvanism was used for management of numerous illnesses including depression by placing the voltaic pile on the parietal
region of the head (Figure 2) [9].
In 1825, the French physician Jean-Baptiste Sarlandière demonstrated that the effect
of Galvanism could be enhanced by use of
acupuncture needles leading to the first development of electro-acupuncture. He resumed:
“... in my opinion electro-acupuncture is the
most proper method of treating rheumatism,
nervous afflictions and attacks of gout …”
[9]. It should be mentioned that before Sarlandière, the French physician and composer,
Hector Berlioz, suggested the combination of
classic Chinese method of acupuncture with
electrotherapy. He mentioned that “apparently
the application of Galvanic shock produced
by the voltaic pile heightens the medical effect of acupuncture” [9].
Application of Galvanic current was not
without side effects. Its prolonged use led to
necrotic changes in the tissues. This damaging
action was later employed for destruction of
superficial tumors including prostate cancer.
The third phase was the introduction of
Faradism. The British scientist, Michael
Faraday, in 1832 employed the voltaic pile
Figure 3. Illustration of the voltaic pile, the first
battery consisting of copper and zinc, separated by
electrolyte solution to increase the conductivity
(Adolphe Ganot in Elementary Treatise on Physics:
Experimental and Applied 1893).
and discovered that the flow of electricity
could be induced intermittently (interrupted)
and in alternate directions. Stimulations were
performed with a short pulse duration (< 1
millisecond), thereby preventing any risk of
tissue damage. The most important promoter of Faradism in the mid 19th century was
the French physician, Guillaume Duchenne,
(“father of electrotherapy”), who used this
technique in particular for muscle stimulation. In 1849 he stated “Faradism is the best
form of muscular electricity and can be practiced frequently and for a long time… The
results are of highest importance” [8].
The fourth phase was the discovery of
high frequency currents by the French physician, Jacques Arsène d`Arsonval, in 1888
who observed that frequencies beyond 5.000
Hz decreased the excitation of muscles [8].
Throughout the 19th century the analgesic
effects of electricity were widely popular and
enjoyed their “golden age”. Electrotherapy
was used for countless dental, neurological,
psychiatric and gynecological disturbances.
It was even used by quacks and charlatans
for enhancing health and beauty with the slogan “vibrate your body and make it well”.
With regard to these unserious applications,
electricity fell into disregard more and more.
Neuromuscular electrostimulation techniques: historical aspects and effects
S15
Figure 4. Output characteristics (settings) of a standard TENS device. The user can control the amplitude
(intensity), duration (width), frequency (rate) and pattern (mode) of the pulsed electrical currents.” With
permission from Tashani and Johnson (2009) [14].
Another cause of the declined interest was
the advance of potent analgesic drugs.
Modern development of neuromuscular stimulation
In the second half of the 20th century,
the scientific bases of electrotherapy was
increasingly elucidated, offering the chance
for a rational treatment of various painful
conditions. The new techniques included
transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve
stimulation (PENS) and spinal cord stimulation (SCS). In 2005 the so-called high
tone external muscle stimulation (HTEMS)
was introduced to combat pain. The electrical devices differ in regard to the amplitude
(intensity), frequency, duration and pattern
of the electrical currents (Figure 4).
Transcutaneous electrical
nerve stimulation
TENS is currently the most frequent form
of non-pharmacological pain management.
It is based on the observation by Wall and
Sweat in 1967 [12] that an electrical stimulation with 100 Hz applied on the skin surface
resulted in a dramatic relief of pain. TENS
consists of a battery-powered portable electric unit with electrodes applied to the skin,
delivering electrical impulses to the underlying nerve fibers. Different kinds of frequency
modes are: high frequency (HF-TENS > 50
Hz), low frequency (LF-TENS < 10 Hz)
and variable frequency (VF-TENS) [13].
The intensity is usually adjustable. After application of HF-TENS intensity is generally
low (low pulse amplitude), associated with a
non-painful feeling of tingling. On the other
hand, application of LF-TENS is associated
with a high intensity (high pulse amplitude)
resulting in strong, but mostly comfortable
muscle twitching. Pain relief after TENS
may be rapid, but initially the effects are not
long-lasting.
PENS (acupuncture-like TENS) combines the effect of both LF- TENS (usually
2 pps and high intensity) and acupuncturelike needle probes leading to a transcutaneous hyperstimulation [15]. Administration
is performed over muscles, acupuncture and
trigger points. In general about ten 32 gauge
needle probes are used [16].
Spinal cord stimulation (SCS) is an invasive method. The electrode is implanted in
the epidural space and exerts pulsed electrical signals directly to the spinal cord. The
electrical pulse generator is placed in the
lower abdominal area. In 1967, the dorsal
horn of the spinal cord was stimulated for the
first time by Shealy and Mortinor [17]. In the
following years, its marked effects led to the
development of implanted electrodes with a
modern radiofrequency receiver. SCS is indi-
Heidland, Fazeli, Klassen et al.
S16
trol mechanisms, TENS application in cats
reduced the activity of dorsal horn cells which
was evoked spontaneously or noxiously [20].
Besides the segmental inhibition of pain in
the dorsal horn, Melzack and Wall also suggested that an activation of descending pain
inhibitory mechanisms is implicated in the
analgesic action of electricity. The role of this
pathway was underlined by two observations:
first, the analgesic action of HF-TENS was
partly reduced by cutting of the spinal cord
(spinalization), which removes the descending inhibitory components [21] and second, the
analgesic effect of TENS outlasts the time of
stimulation by several hours, implicating the
involvement of extra-segmental factors [13].
Figure 5. The hypothetical gate of the pain mechanism. Activation of small nociceptive fibers holds
the gate open, while activation of large mechanoreceptive fibers closes the gate and inhibits pain
transmission to the brain.
cated to control severe chronic pain, which is
unresponsive to other kinds of therapy.
Potential mechanisms involved
in the analgesic action of
electrical stimulation
In 1965 Melzack and Wall [18] developed
the Gate Control Theory of Pain. The authors
suggested that “the substantia gelatinosa in
the dorsal horn acts as a gate control system,
which modulates the synaptic transmission of
nerve impulses from peripheral fibers to the
central cells.” According to this hypothesis
the small nociceptive A-δ and C fibers hold
the hypothetical gate in a relative opened position, while stimulation of the large mechanoreceptive A-β fibers (which are stimulated
by touch, pressure or vibration) close the gate
and inhibit the pain transmission to the brain.
Because small nociceptive fibers are characterized by a higher threshold of action than
the large mechanoreceptive fibers, the selective stimulation of the latter ones can prevent
or reduce pain transmission (Figure 5). The
concept of Melzack and Wall led to the application of gentle electrical stimulation to electrode taped to the skin, the later called TENS
[19]. In line with the concept of the gate con-
The descending pathway originates in
the midbrain and starts in the periaqueductal grey (PAG), which sends projections
to the rostral ventral medulla (RVM), followed by projections to the spinal dorsal
horn [22, 23]. TENS-induced activation of
PAG and RVM is involved in the reduction
of hyperalgesia in arthritic rats [22]. Of
particular importance is the enhanced release of endogenous opioids and serotonin,
which act through the PAG-RVM pathway
[24]. In the spinal fluid of arthritic rats LFTENS enhanced the levels of µ-opioids,
while HF-TENS increased the δ-opioids
concentrations. Pre-treatment of these rats
with the µ-opioid receptor antagonist, naloxone, blocked the effect of LF-TENS,
while the δ-opioid receptor antagonist,
naltrindole, prevented the action of HFTENS [25]. Furthermore in humans, HFand LF-TENS application is associated
with enhanced levels of β-endorphin, both
in spinal fluid and blood plasma [26, 27].
Serotonin exerts its analgesic action supraspinally and spinally, depending on the
activated receptor type and the used dose
[28]. Correspondingly, in brain homogenates its concentration was elevated. The
effect of HF-TENS is enhanced by application of serotonin and reduced by its depletion. Norepinephrine is antinociceptive in
the PAG-RVM pathway and in the spinal
dorsal horn by activating α2-adrenoceptors
[29]. In the analgesic action of electricity,
adenosine is implicated via activation of purinergic (adenosine) receptors at peripheral
and spinal sites [30].
Neuromuscular electrostimulation techniques: historical aspects and effects
An important factor in TENS-induced
analgesia is the neuroinhibitory transmitter
GABA as shown in arthritic rats. HF-TENS
enhanced the release of GABA in the deep
dorsal horn of the spinal cord and both HFand LF-TENS reduced the hyperalgesia by
activation of spinal GABA-A receptors [31].
Moreover, SCS produces in the dorsal
horn an augmented release of acetylcholine,
indicating an activation of the cholinergic
system in the analgesic effect [32].
In arthritic rats HF-TENS, but not LFTENS, lowered the levels of some excitatory
amino acids such as glutamate and aspartate
in the dorsal horn [33].
TENS also reduces the production of substance P in this region [34]. Several lines of
evidence suggest that the motor-cortex excitability can be modulated by peripheral nerve
stimulation with LF- and HF-TENS [35].
Daily administration of TENS is followed
by an analgesic tolerance at the spinal opioid
receptor as early as on the 4th day [36]. Recent data suggest that this tolerance can be
delayed or prevented by simultaneous activation of µ-opioid and δ-opioid receptors.
Therefore, either a mixed frequency (HFand LF-TENS at the same session) or an alternating frequency (HF- and LF-TENS) applied separately on alternating days) should
be used [37].
Circulatory effects of
electrotherapy
According to laser Doppler investigations, TENS application in healthy volunteers stimulates the peripheral microcirculation [38], potentially contributing to
the analgesic action of TENS. In diabetic
neuropathy, a relationship between capillary abnormalities and severity of neuropathy has been observed [39]. In these
patients TENS-induced vasodilation is associated with the enhanced microcirculation and increased endoneural blood flow
[40]. Electrotherapy, in particular in the
form of SCS, enhances the blood flow in
ischemic peripheral vascular and coronary heart disease [41]. The vasodilation
may be induced by release of vasoactive
substances such as calcitonin gene-related
peptide and possibly nitric oxide (NO) [42,
S17
43, 44]. In certain conditions an inhibition
of sympathetic afferent activity may contribute to vasodilation [45].
Clinical trials of various types
of electrotherapy
Transcutaneous electrical nerve
stimulation
The effectiveness of TENS was shown in
many clinical studies. However, in numerous
investigations evidence of TENS was inconclusive due to short-comings of the randomized clinical trials (RCTs), among others due
to poor classification of the patient groups
and lack of standardization of the therapy
etc. Moreover, the possibility of tolerance
to TENS has to be considered in the case of
negative results. In diabetic polyneuropathy
three RCTs were performed with positive
results. In the first placebo-controlled RCT
of 31 patients with type II diabetes, TENS
improved the painful distal polyneuropathy
significantly [46]. The same authors likewise
demonstrated that TENS in combination
with amitriptyline appears to be “a useful adjunctive modality” [47]. In a third RCT of a
German research group, the effect of TENS
was significant [48].
Analgesic effects of TENS have also
been reported in pain caused by knee osteoarthritis [49], which was not confirmed in a
recent RCT [50]. In the treatment of lower
back pain beneficial effects of TENs have
been reported [51]. However, according to
Cochrane database the treatment with TENS
for lower back pain seems not to be effective
[52]. TENS was shown to be beneficial for
pain caused by renal colic in the emergency
care unit [53]. These data correspond to an
experimental visceral model of renal pain
in cats, induced by occlusion of the ureter
or renal artery [54]. Moreover, after various
surgical procedures the analgesic effects of
TENS seem to be significant [55].
Intermittent use of TENS is recommended for patients with acquired polycystic kidney disease (APKD), who frequently suffer
from chronic dull acting pain due to enlargement of the cysts [56]. In cancer-related pain
the data about effectiveness of TENS are still
insufficient (Cochrane review) [57].
S18
Heidland, Fazeli, Klassen et al.
Interestingly, TENS was reported to be
beneficial in severe angina pectoris [58]. In
another study LF-TENS lowered the blood
pressure [59]. It was even successfully applied in a small group of patients with therapy-resistant hypertension, as documented
by 24-h blood pressure measurements [60].
This effect appears to be partly due to inhibition of the central sympathetic activity.
Recently, the blood pressure lowering actions of TENS could not be confirmed [61].
Percutaneous electrical nerve
stimulation
In a sham-controlled cross-over study,
PENS lowered pain from diabetic peripheral
neuropathy and improved the physical activity of the patients. Also mental components
of the SF-36 showed improvements compared to sham [62]. In another sham-controlled crossover study in patients with lower
back pain PENS was more effective than
TENS [16]. It is also reported that PENS is
effective in post-herpetic neuropathy, severe
sciatica and lower back pain (among others
due to bone metastasis).
Spinal cord stimulation
The efficacy of SCS in neuropathic pain
of diabetic patients has been demonstrated
in a prospective randomized controlled
multicenter trial with a 24-month follow-up
[63]. It is well established in the treatment
of failed back surgery syndrome (FBSS) and
the complex regional pain syndrome (CRPS)
[64, 65]. In an earlier study in patients with
multiple sclerosis, SCS improved the spasticity [66].
SCS was very successful in patients with
severe intractable angina pectoris (unsuitable
for coronary artery bypass grafting – CABG
or percutaneous laser revascularization). Results showed improvements in chest pain,
less ST segment depression, augmented
myocardial blood flow and enhanced exercise capacity [67]. Notably, SCS was as effective as CABG surgery [68]. Its beneficial
long-term actions on angina pectoris were
recently confirmed [69].
Also in patients with ischemic peripheral artery disease (unsuitable for vascular
reconstruction) SCS was successfully applied [70]. It markedly alleviated pain and
delayed or even prevented amputations [71].
In dialysis patients with critical lower limb
ischemia (Leriche-Fountain Stage 3 or 4),
SCS dramatically improved pain and quality
of life [72]. The benefits persisted for up to
6 – 12 months and are also attributed to an
improved microvascular blood flow of the
legs [73].
However, SCS does not come without
complications: The device fails in 3 – 4% of
the cases, and 3 – 5% of the patients develop
infections [74]. Most frequently, the external electrode is either dislocated or broken
(11 – 36%).
In recent animal models of Parkinson’s
disease, SCS restored the locomotion [75].
Conceivably, it could be helpful also in patients suffering from severe Parkinson’s disease, who are currently treated with the more
invasive electrical deep brain stimulation.
High tone external muscle
stimulation
HTEMS is a new device for pain treatment. With this method a continuous scan of
the carrier frequency, varying in short intervals between 4,096 and 32,786 Hz, is applied.
The amplitude and frequency are modulated
simultaneously. In a short-term comparative
study (3 consecutive days for 30 min) between TENS and HTEMS in painful diabetic
polyneuropathy, HTEMS was nearly three
times more effective than TENS in relieving pain symptoms and discomfort [76]. The
analgesic action was recently confirmed and
extended [77]. In a prospective uncontrolled
study (twice weekly 60 min sessions, for 4
weeks) in 92 Type 2 diabetic patients with
peripheral neuropathy, a marked improvement of pain and of sleeping disturbances
was observed in 73% of the patients.
Our group investigated in a pilot study
the effect of HTEMS in dialysis patients with
symptomatic peripheral polyneuropathy (25
patients with diabetic and 15 with uremic
peripheral polyneuropathy) [78]. Electrodes
were placed on the femoral muscles. The patients were treated intradialytically for up to
Neuromuscular electrostimulation techniques: historical aspects and effects
Figure 6. Effects of HTEMS on five neuropathic
symptoms and on sleeping disorder in maintenance hemodialysis patients. **p < 0.005. Reproduced from Klassen et al. [78].
60 min, three times a week. After a period of
1 – 3 months, more than 70% of the patients
reported a significant improvement of neuropathic symptoms and sleep disturbances
(Figure 6) [78]. In a subgroup of 12 dialysis
patients with diabetic polyneuropathy, the
effect was followed for 12 months [79]. In
these individuals the beneficial action of
HTEMS remained significant as compared
to baseline with exception of sleeping disorders.
It is well known that placebos are very
effective in the treatment of pain. However,
their effects diminish with repeated administration. Therefore, the persistence of the
analgesic action of HTEMS over a period of
one year is a strong indicator of the impact
of this kind of therapy. Meanwhile, the efficacy of HTEMS in dialysis patients with peripheral neuropathy has been confirmed and
extended [80].
According to recent studies of our group,
HTEMS treatment of painful neuropathy in
dialysis patients is associated with an improvement of some components of Short
Form of the SF-36 questionnaire [81].
Electrical muscle stimulation for
prevention and treatment of
muscle wasting
In 1988 Gibson at al. [82] postulated
that in rheumatic arthritis the motor fibers
should be stimulated electrically in order
S19
to prevent muscle atrophy and to restore
muscle function. In a subsequent study,
TENS was associated with increased muscle function as evaluated by a Hand-Grip
test [83]. In the last decade further developments led to functional electrical stimulation (FES), in particular in patients with
spinal cord damage.
An important indication for electrotherapy is sarcopenia which is defined as loss
of muscle mass and weakness. Sarcopenia
is a frequent complication in ESRD, chronic heart failure, diabetes mellitus, obesity,
cancer and old age. It is a critical factor in
normal daily activity and associated with
a high risk for falls and fractures with enhanced morbidity and mortality. Myopathy
typically affects the proximal muscles of
the thighs, while peripheral neuropathy
causes muscle loss of the lower legs [84].
The most important causes of sarcopenia
in ESRD are uremic toxins, deficiency of
vitamin D and of carnitine, secondary hyperparathyroidism, poor nutritional state,
vascular ischemia, metabolic acidosis,
muscle unloading due to physical inactivity and immobilization, and enhanced insulin resistance [85].
In the therapy of sarcopenia, besides
correction of the altered biochemical parameters, physical exercise is of fundamental importance [86], in particular with
regard to an improved insulin resistance
[87]. However, training is often difficult to
realize due to severe co-morbid conditions.
In these individuals electrical myostimulation (EMS) might be an alternative, as it
mimics various effects of active exercise.
EMS (20 Hz) increases muscle oxidative
capacity [88] and enhances glucose disposal [89]. In paraplegic patients, EMS of the
paralyzed muscles (3 days per week for 8
weeks) enhanced expression of the GLUT1 and GLUT-4 transporters, oxidative capacity, and insulin sensitivity [90].
In the past several years EMS has proven
quite effective in the treatment of sarcopenia of patients with chronic heart failure. In
a randomized clinical trial TENS (low frequency) of the upper legs for 10 weeks (2
times for 2 h per day) enhanced the peak
exercise capacity and oxygen consumption
considerably, while the corresponding values in the Sham TENS group remained un-
S20
Heidland, Fazeli, Klassen et al.
changed [91]. Similar results were obtained
in another randomized study of home-based
EMS of the legs and conventional bicycle
exercise training in chronic heart failure
[92]. Also in patients with chronic obstructive pulmonary disease application of EMS
improved muscle function significantly [93].
Recently, in a randomized trial in ESRD
patients, the effect of intradialytic EMS (frequency of 10 Hz) of leg extensors was investigated and compared to both intradialytic
active exercise training (on a bicycle ergometer) and to an untreated control group of
dialysis patients [94]. After 20 weeks EMS
exerted pronounced effects on functional
muscle capacity and mental components of
quality of life. In many aspects, EMS was
comparable to the group performing active
exercise [94]. Interestingly, intradialytic
EMS was associated with an enhanced removal rate of urea and inorganic phosphate.
The effect was comparable to the group performing intradialytic active exercise.
Up to now the effects of intradialytic
HTEMS on muscle function have not been
investigated. However, some patients reported spontaneously about an improved
strength of the legs and an easier stairclimbing after long-term HTEMS. Moreover, there are data that HTEMS improves
the insulin resistance which is an important
risk factor of muscle wasting. In a study in
obese diabetic individuals, daily application
of HTEMS (1 h) for 6 weeks ameliorated
the elevated HbA1c levels and lowered the
body weight [95], suggesting an improved
insulin resistance.
Currently, there are only few contra-indications for electrotherapy. These include
active bacterial infection, presence of a pacemaker or cardiac defibrillator, pregnancy, recent fractures, acute thrombosis and epilepsy.
Summarizing, in the last decades electroneuro-muscular stimulation improved the
therapy of various kinds of pain and sarcopenia and was associated with the reduction of
needed medications. In the case of HTEMS
despite the current lack of RTCs, the available clinical data support its benefits. In
particular in ESRD patients its application
during dialysis has the advantage that the
patients do not need any extra time for this
treatment.
Conflict of interest
A.H. received lecture honoraria from
gbo. The other authors declare no conflict of
interest.
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
Murken AH. Pain as man’s constant companion
from birth to death. Verlag Murken Altrogge,
2005.
Davison SN. Pain in hemodialysis patients: prevalence, cause, severity, and management. Am J
Kidney Dis. 2003; 42: 1239-1247.
Bailie GR, Mason NA, Bragg-Gresham JL, Gillespie BW, Young EW. Analgesic prescription patterns among hemodialysis patients in the DOPPS:
potential for underprescription. Kidney Int. 2004;
65: 2419-2425.
Schechter DC. Origins of electrotherapy. I. N Y
State J Med. 1971; 71: 997-1008.
Ose R. Elektrizität im alten Ägypten? In Erich
von Däniken: Jäger verlorenen Wissens, Kopp
Verlag; Rottenburg. 2003. p. 69-78
Rossi U. The history of electrical stimulation of
the nervous system for the control of pain. Electrical stimulation and the relief of pain. Edited by
Simpson BA, Elsevier BV 2003. p. 6 - 16
Perdikis P. Transcutaneous nerve stimulation in
the treatment of protracted ileus. S Afr J Surg.
1977; 15: 81-86.
Turrell WJ. The landmarks of electrotherapy.
Arch Phys Med Rehabil. 1969; 50: 157-160.
Stillings D. A survey of the history of electrical
stimulation for pain to 1900. Med Instrum. 1975;
9: 255-259.
Macdonald AJR. A brief review of the history of
electrotherapy and its union with acupuncture.
Acupunct Med. 1999; 11: 66-75.
Garratt AC. Franklinism or atmospheric electricity as remedy. Boston Med Surg J. 1883; 108:
123-125.
Wall PD, Sweet WH. Temporary abolition of pain
in man. Science. 1967; 155: 108-109.
Sluka KA, Walsh D. Transcutaneous electrical
nerve stimulation: basic science mechanisms and
clinical effectiveness. J Pain. 2003; 4: 109-121.
Tashani O, Johnson MJ. Transcutaneous electrical nerve stimulation (TENS) a possible aid for
pain relief in developing countries? Libyan J
Med. 2009; 4: 62-65.
Johnson M. The analgesic effects and clinical use
of Acupuncture – like TENS (AL – TENS). Phys
Ther Rev. 1998; 3: 73-93.
Ghoname EA, Craig WF, White PF, Ahmed HE,
Hamza MA, Henderson BN, Gajraj NM, Huber
PJ, Gatchel RJ. Percutaneous electrical nerve
stimulation for low back pain: a randomized
crossover study. JAMA. 1999; 281: 818-823.
Shealy CN, Mortimer JT, Reswick JB. Electrical
inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg.
1967; 46: 489-491.
Melzack R, Wall PD. Pain mechanisms: a new
theory. Science. 1965; 150: 971-979.
Neuromuscular electrostimulation techniques: historical aspects and effects
[19] Gildenberg PL. History of Electrical neuromodulation of chronic pain. Pain Medicine. 2006; 7:
S7-S13.
[20] Garrison DW, Foreman RD. Decreased activity of
spontaneous and noxiously evoked dorsal horn
cells during transcutaneous electrical nerve stimulation (TENS). Pain. 1994; 58: 309-315.
[21] Woolf CJ, Mitchell D, Barrett GD. Antinociceptive effect of peripheral segmental electrical stimulation in the rat. Pain. 1980; 8: 237-252.
[22] DeSantana JM, Walsh DM, Vance C, Rakel BA,
Sluka KA. Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia
and pain. Curr Rheumatol Rep. 2008; 10: 492-499.
[23] DeSantana JM, Da Silva LF, De Resende MA,
Sluka KA. Transcutaneous electrical nerve stimulation at both high and low frequencies activates
ventrolateral periaqueductal grey to decrease mechanical hyperalgesia in arthritic rats. Neuroscience. 2009; 163: 1233-1241.
[24] Sabino GS, Santos CM, Francischi JN, de Resende MA. Release of endogenous opioids following transcutaneous electric nerve stimulation in an
experimental model of acute inflammatory pain. J
Pain. 2008; 9: 157-163.
[25] Kalra A, Urban MO, Sluka KA. Blockade of opioid receptors in rostral ventral medulla prevents
antihyperalgesia produced by transcutaneous
electrical nerve stimulation (TENS). J Pharmacol
Exp Ther. 2001; 298: 257-263.
[26] Salar G, Job I, Mingrino S, Bosio A, Trabucchi M.
Effect of transcutaneous electrotherapy on CSF
beta-endorphin content in patients without pain
problems. Pain. 1981; 10: 169-172.
[27] Hughes GS Jr, Lichstein PR, Whitlock D, Harker
C. Response of plasma beta-endorphins to transcutaneous electrical nerve stimulation in healthy
subjects. Phys Ther. 1984; 64: 1062-1066.
[28] Schmauss C, Hammond DL, Ochi JW, Yaksh TL.
Pharmacological antagonism of the antinociceptive effects of serotonin in the rat spinal cord. Eur
J Pharmacol. 1983; 90: 349-357.
[29] Yaksh TL. Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing.
Pharmacol Biochem Behav. 1985; 22: 845-858.
[30] Sawynok J. Adenosine receptor activation and nociception. Eur J Pharmacol. 1998; 347: 1-11.
[31] Maeda Y, Lisi TL, Vance CG, Sluka KA. Release
of GABA and activation of GABA(A) in the spinal cord mediates the effects of TENS in rats.
Brain Res. 2007; 1136: 43-50.
[32] Schechtmann G, Song Z, Ultenius C, Meyerson
BA, Linderoth B. Cholinergic mechanisms involved in the pain relieving effect of spinal cord
stimulation in a model of neuropathy. Pain. 2008;
139: 136-145.
[33] Sluka KA, Vance CG, Lisi TL. High-frequency, but
not low-frequency, transcutaneous electrical
nerve stimulation reduces aspartate and glutamate
release in the spinal cord dorsal horn. J Neurochem. 2005; 95: 1794-1801.
[34] Rokugo T, Takeuchi T, Ito H. A histochemical
study of substance P in the rat spinal cord: effect
of transcutaneous electrical nerve stimulation. J
Nihon Med Sch. 2002; 69: 428-433.
[35] Tinazzi M, Zarattini S, Valeriani M, Romito S, Farina S, Moretto G, Smania N, Fiaschi A, Abbruzzese G. Long-lasting modulation of human motor
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
S21
cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation. Exp Brain Res. 2005; 161: 457-464.
Chandran P, Sluka KA. Development of opioid
tolerance with repeated transcutaneous electrical
nerve stimulation administration. Pain. 2003;
102: 195-201.
DeSantana JM, Santana-Filho VJ, Sluka KA.
Modulation between high- and low-frequency
transcutaneous electric nerve stimulation delays
the development of analgesic tolerance in arthritic
rats. Arch Phys Med Rehabil. 2008; 89: 754-760.
Wikström SO, Svedman P, Svensson H, Tanweer
AS; Sven Olof Wikström, Paul Svedman, H. Effect
of transcutaneous nerve stimulation on microcirculation in intact skin and blister wounds in
healthy volunteers. Scand J Plast Reconstr Surg
Hand Surg. 1999; 33: 195-201.
Malik RA, Newrick PG, Sharma AK, Jennings A,
Ah-See AK, Mayhew TM, Jakubowski J, Boulton
AJ, Ward JD. Microangiopathy in human diabetic
neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetologia. 1989; 32: 92-102.
Kaada B. Vasodilation induced by transcutaneous
nerve stimulation in peripheral ischemia (Raynaud’s phenomenon and diabetic polyneuropathy).
Eur Heart J. 1982; 3: 303-314.
Kaada B, Vik-mo H, Rosland G, Woie L, Opstad
PK. Transcutaneous nerve stimulation in patients
with coronary arterial disease: haemodynamic
and biochemical effects. Eur Heart J. 1990; 11:
447-453.
Croom JE, Foreman RD, Chandler MJ, Koss MC,
Barron KW. Role of nitric oxide in cutaneous
blood flow increases in the rat hindpaw during
dorsal column stimulation. Neurosurgery. 1997;
40: 565-570.
Göksel HM, Karadag O, Turaçlar U, Taş F, Oztoprak I. Nitric oxide synthase inhibition attenuates
vasoactive response to spinal cord stimulation in
an experimental cerebral vasospasm model. Acta
Neurochir (Wien). 2001; 143: 383-390.
Tanaka S, Barron KW, Chandler MJ, Linderoth B,
Foreman RD. Role of primary afferents in spinal
cord stimulation-induced vasodilation: characterization of fiber types. Brain Res. 2003; 959: 191198.
Foreman RD, Linderoth B, Ardell JL, Barron KW,
Chandler MJ, Hull SS Jr, TerHorst GJ, DeJongste
MJ, Armour JA. Modulation of intrinsic cardiac
neurons by spinal cord stimulation: implications
for its therapeutic use in angina pectoris. Cardiovasc Res. 2000; 47: 367-375.
Kumar D, Marshall HJ. Diabetic peripheral neuropathy: amelioration of pain with transcutaneous
electrostimulation. Diabetes Care. 1997; 20: 17021705.
Kumar D, Alvaro MS, Julka IS, Marshall HJ. Diabetic peripheral neuropathy. Effectiveness of electrotherapy and amitriptyline for symptomatic relief. Diabetes Care. 1998; 21: 1322-1325.
Forst T, Nguyen M, Forst S, Disselhoff B, Pohlmann T, Pfützner A. Impact of low frequency
transcutaneous electrical nerve stimulation on
symptomatic diabetic neuropathy using the new
Heidland, Fazeli, Klassen et al.
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]
[62]
Salutaris device. Diabetes Nutr Metab. 2004; 17:
163-168.
Osiri M, Welch V, Brosseau L, Shea B, McGowan
J, Tugwell P, Wells G. Transcutaneous electrical
nerve stimulation for knee osteoarthritis. Cochrane Database Syst Rev. 2000; CD002823
Vance CG, Rakel BA, Blodgett NP, Desantana JM,
Amendola A, Zimmerman MB, Walsh DM, Sluka
KA. Effects of transcutaneous electrical nerve
stimulation on pain, pain sensitivity, and function in people with knee osteoarthritis: a randomized controlled trial. Phys Ther. 2012; 92:
898-910.
Melzack R, Vetere P, Finch L. Transcutaneous
electrical nerve stimulation for low back pain. A
comparison of TENS and massage for pain and
range of motion. Phys Ther. 1983; 63: 489-493.
Milne S, Welch V, Brosseau L, Saginur M, Shea B,
Tugwell P, Wells G. Transcutaneous electrical
nerve stimulation (TENS) for chronic low back
pain. Cochrane Database Syst Rev. 2001;
CD003008.
Mora B, Giorni E, Dobrovits M, Barker R, Lang
T, Gore C, Kober A. Transcutaneous electrical
nerve stimulation: an effective treatment for pain
caused by renal colic in emergency care. J Urol.
2006; 175: 1737-1741.
Nam TS, Baik EJ, Shin YU, Jeong Y, Paik KS.
Mechanism of transmission and modulation of
renal pain in cats; effects of transcutaneous electrical nerve stimulation on renal pain. Yonsei Med
J. 1995; 36: 187-201.
Bjordal JM, Johnson MI, Ljunggreen AE. Transcutaneous electrical nerve stimulation (TENS)
can reduce postoperative analgesic consumption.
A meta-analysis with assessment of optimal treatment parameters for postoperative pain. Eur J
Pain. 2003; 7: 181-188.
Bajwa ZH, Gupta S, Warfield CA, Steinman TI.
Pain management in polycystic kidney disease.
Kidney Int. 2001; 60: 1631-1644.
Robb K, Oxberry SG, Bennett MI, Johnson MI,
Simpson KH, Searle RD. A cochrane systematic
review of transcutaneous electrical nerve stimulation for cancer pain. J Pain Symptom Manage.
2009; 37: 746-753.
Mannheimer C, Carlsson CA, Ericson K, Vedin A,
Wilhelmsson C. Transcutaneous electrical nerve
stimulation in severe angina pectoris. Eur Heart J.
1982; 3: 297-302.
Kaada B, Flatheim E, Woie L. Low-frequency
transcutaneous nerve stimulation in mild/moderate
hypertension. Clin Physiol. 1991; 11: 161-168.
Jacobsson F, Himmelmann A, Bergbrant A,
Svensson A, Mannheimer C. The effect of transcutaneous electric nerve stimulation in patients with
therapy-resistant hypertension. J Hum Hypertens.
2000; 14: 795-798.
Silverdal J, Mourtzinis G, Stener-Victorin E,
Mannheimer C, Manhem K. Antihypertensive effect of low-frequency transcutaneous electrical
nerve stimulation (TENS) in comparison with drug
treatment. Blood Press. 2012; epub ahead of print.
Hamza MA, White PF, Craig WF, Ghoname ES,
Ahmed HE, Proctor TJ, Noe CE, Vakharia AS,
Gajraj N. Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. Diabetes Care. 2000; 23: 365-370.
S22
[63] Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio
M, Molet J, Thomson S, O’Callaghan J, Eisenberg E, Milbouw G, Buchser E, Fortini G, Richardson J, North RB. The effects of spinal cord
stimulation in neuropathic pain are sustained: a
24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery.
2008; 63: 762-770.
[64] Kunnumpurath S, Srinivasagopalan R, Vadivelu
N. Spinal cord stimulation: principles of past,
present and future practice: a review. J Clin Monit
Comput. 2009; 23: 333-339.
[65] Prager JP. What does the mechanism of spinal
cord stimulation tell us about complex regional
pain syndrome? Pain Med. 2010; 11: 1278-1283.
[66] Cook AW. Electrical stimulation in multiple sclerosis. Hosp Pract. 1976; 11: 51-58.
[67] Mannheimer C, Augustinsson LE, Carlsson CA,
Manhem K, Wilhelmsson C. Epidural spinal electrical stimulation in severe angina pectoris. Br
Heart J. 1988; 59: 56-61.
[68] Mannheimer C, Eliasson T, Augustinsson LE,
Blomstrand C, Emanuelsson H, Larsson S, Norrsell H, Hjalmarsson A. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study. Circulation. 1998;
97: 1157-1163.
[69] Eckert S, Horstkotte D. Management of angina
pectoris: the role of spinal cord stimulation. Am J
Cardiovasc Drugs. 2009; 9: 17-28.
[70] Klomp HM, Spincemaille GH, Steyerberg EW,
Habbema JD, van Urk H; ESES Study Group.
Spinal-cord stimulation in critical limb ischaemia:
a randomised trial. Lancet. 1999; 353: 1040-1044.
[71] Oakley JC, Prager JP. Spinal cord stimulation:
mechanisms of action, Spine (Phila Pa 1976).
2002; 27: 2574-2583.
[72] Brümmer U, Condini V, Cappelli P, Di Liberato L,
Scesi M, Bonomini M, Costantini A. Spinal cord
stimulation in hemodialysis patients with critical
lower-limb ischemia. Am J Kidney Dis. 2006; 47:
842-847.
[73] Jacobs MJ, Jörning PJ, Joshi SR, Kitslaar PJ,
Slaaf DW, Reneman RS. Epidural spinal cord electrical stimulation improves microvascular blood
flow in severe limb ischemia. Ann Surg. 1988;
207: 179-183.
[74] Torrens JK, Stanley PJ, Ragunathan PL, Bush DJ.
Risk of infection with electrical spinal-cord stimulation. Lancet. 1997; 349: 729.
[75] Fuentes R, Petersson P, Siesser WB, Caron MG,
Nicolelis MA. Spinal cord stimulation restores locomotion in animal models of Parkinson’s disease. Science. 2009; 323: 1578-1582.
[76] Reichstein L, Labrenz S, Ziegler D, Martin S. Effective treatment of symptomatic diabetic polyneuropathy by high-frequency external muscle
stimulation. Diabetologia. 2005; 48: 824-828.
[77] Humpert PM, Morcos M, Oikonomou D, Schaefer
K, Hamann A, Bierhaus A, Schilling T, Nawroth
PP. External electric muscle stimulation improves
burning sensations and sleeping disturbances in
patients with type 2 diabetes and symptomatic
neuropathy. Pain Med. 2009; 10: 413-419.
[78] Klassen A, Di Iorio B, Guastaferro P, Bahner U,
Heidland A, De Santo N. High-tone external muscle stimulation in end-stage renal disease: effects
Neuromuscular electrostimulation techniques: historical aspects and effects
[79]
[80]
[81]
[82]
[83]
[84]
[85]
[86]
[87]
[88]
[89]
[90]
[91]
[92]
[93]
on symptomatic diabetic and uremic peripheral
neuropathy. J Ren Nutr. 2008; 18: 46-51.
Klassen A, Di Iorio B, Guastaferro P, et al. Shortand long-term results of high-tone external muscle stimulation in symptomatic diabetic and uremic peripheral polyneuropathy in end-stage renal
disease. Third international congress on neuropathic pain, Athens, Greece, 2010, Abstract p. 40
Strempska B, Bilinska M, Weyde et al. The effect
of High-tone electrical muscle stimulation on the
symptoms and electrophysiological parameters of
the uremic peripheral neuropathy. Clin Nephrol.
2012; 78 (suppl 1): S24-S27.
Klassen A, Racasan S, Blaser C et al. High tone
external muscle stimulation: effects on quality of
life in patients with peripheral neuropathy. Clin
Nephrol. 2012; 78 (suppl 1): S28-S33.
Gibson JN, Smith K, Rennie MJ. Prevention of
disuse muscle atrophy by means of electrical
stimulation: maintenance of protein synthesis.
Lancet. 1988; 2: 767-770.
Oldham JA, Stanley JK. Rehabilitation of atrophied muscle in the rheumatoid arthritic hand: a
comparison of two methods of electrical stimulation. J Hand Surg [Br]. 1989; 14: 294-297.
Ritz E, Schoemig M, Massry SG. Uremic myopathy, in Textbook of Nephrology, edited by Massry
and Glassock, Fourth edition, 2001, 1426-1429
Hung AM, Ikizler TA. Factors determining insulin
resistance in chronic hemodialysis patients. Contrib Nephrol. 2011; 171: 127-134.
Koh KP, Fassett RG, Sharman JE, Coombes JS,
Williams AD. Effect of intradialytic versus homebased aerobic exercise training on physical function and vascular parameters in hemodialysis patients: a randomized pilot study. Am J Kidney Dis.
2010; 55: 88-99.
Houmard JA, Tanner CJ, Slentz CA, Duscha BD,
McCartney JS, Kraus WE. Effect of the volume
and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004; 96: 101-106.
Martin TP, Stein RB, Hoeppner PH, Reid DC. Influence of electrical stimulation on the morphological and metabolic properties of paralyzed
muscle. J Appl Physiol. 1992; 72: 1401-1406.
Hamada T, Hayashi T, Kimura T, Nakao K, Moritani T. Electrical stimulation of human lower extremities enhances energy consumption, carbohydrate oxidation, and whole body glucose uptake. J
Appl Physiol. 2004; 96: 911-916.
Chilibeck PD, Bell G, Jeon J, Weiss CB, Murdoch
G, MacLean I, Ryan E, Burnham R. Functional
electrical stimulation exercise increases GLUT-1
and GLUT-4 in paralyzed skeletal muscle. Metabolism. 1999; 48: 1409-1413.
Nuhr MJ, Pette D, Berger R, Quittan M, Crevenna
R, Huelsman M, Wiesinger GF, Moser P, FialkaMoser V, Pacher R. Beneficial effects of chronic
low-frequency stimulation of thigh muscles in
patients with advanced chronic heart failure. Eur
Heart J. 2004; 25: 136-143.
Harris S, LeMaitre JP, Mackenzie G, Fox KA,
Denvir MA. A randomised study of home-based
electrical stimulation of the legs and conventional
bicycle exercise training for patients with chronic
heart failure. Eur Heart J. 2003; 24: 871-878.
Bourjeily-Habr G, Rochester CL, Palermo F, Snyder P, Mohsenin V. Randomised controlled trial of
S23
transcutaneous electrical muscle stimulation of
the lower extremities in patients with chronic obstructive pulmonary disease. Thorax. 2002; 57:
1045-1049.
[94] Dobsak P, Homolka P, Svojanovsky J, Reichertova
A, Soucek M, Novakova M, Dusek L, Vasku J,
Eicher JC, Siegelova J. Intra-dialytic electrostimulation of leg extensors may improve exercise
tolerance and quality of life in hemodialyzed patients. Artif Organs. 2012; 36: 71-78.
[95] Rose B, Lankisch M, Herder C, Röhrig K, Kempf
K, Labrenz S, Hänsler J, Koenig W, Heinemann L,
Martin S. Beneficial effects of external muscle
stimulation on glycaemic control in patients with
type 2 diabetes. Exp Clin Endocrinol Diabetes.
2008; 116: 577-581.