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					Cortical Plasticity: Facilitation of Adelta-fiber-mediated
SEPs in acute pain by high-frequency (100Hz)
repetitive conditioning transcutaneous electrical nerve
stimulation at hand


Li Wang, Lars Arendt-Nielsen, Andrew CN Chen


Human Brain Mapping an Cortical Imaging Laboratory, Center for Sensory-Motor
Interaction, Aalborg University, DK-9220, Aalborg, Denmark




Correspond to: Prof. Andrew CN Chen, Email: ac@smi.auc.dk
Center for Sensory-Motor Interaction (SMI), Aalborg University
Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark
Abstract


In the present study, the effect of the high-frequency (100 Hz) repetitive
conditioning tanscutaneous electrical stimulation (10 min.) on human brain were
investigated, this protocol involved examination of scalp potential amplitude and
dipolar parameters in SEPs to electrical stimulations of thumb (D1) and little
finger (D5) at the noxiously intensive levels. High-density (3D, 124-ch) EEG in
SEPs were recorded (-50 to +450 ms) from 10 healthy male volunteers. Peak
stages 33 ms, 45 ms of Early (0-50 ms), and 212 ms, 331 ms of late phases
(150-450 ms) were analyzed by focal maximum amplitude and area magnitude,
topography, and dipole comparing before and after stimulation. The positive FA
and AM (current efflux) showed a significant increase at early phase 34ms (FA:
F=6.25,p<0.05; AM: F=8.67, p<0.01), and significantly decreased at 45 ms (FA:
F=6.93, p<0.001; AM: F=7.53, p<0.001) on D1 after stimulation. The negative FA
and AM (current influx) significantly increased at the late phase 350 ms on D5
(FA: p<0.001; AM: p=0.01). At 33 ms, the z-axis position of dipole was significant
increased (p<0.05), however, the magnitude of dipole was significant decreased
(p<0.05) on D5. The transcutaneous electrical stimulation results in the different
influence in the early phase, in contrast, the consistent influence can be found at
the late phase of D1 and D5, and made the amplitude of response increased on
the vertical cortex. Grand average result displayed that there was a tendency for
the dipole distance of D1 and D5 at primary somatosensory to be decreased at
34, 45, and 212 ms, but increased at 331ms. This study indicates some likely
effects of cortical plasticity by conditioning somatosensory stimulation in human
brain.


Author Keywords: SEPs; thumb D1; little finger D5; dipole; cortical plasticity.
1. Introduction

1.1 Cortical Plasticity and SEPs




1.2 In-Phase Modulation of SEPs by Peripheral Factors




1.3 Stimulation Induced Post-Effects in SEPs




1.4 Study Aims
2. Methods

2. Materials and methods

2.1. Subjects

Ten right handed healthy male volunteers (mean age: 27.7 years old, range 23-
36 years) participated in this study. All the subjects reported no physical, pain
sensible or mental problems that might limit their ability to participate in the
present experiments. A written consent was obtained from each subject prior to
the experiment according to the Declaration of Helsinki. A verbal description of
the general procedures and cautions were explained carefully to each subject.
The subject was given the option to stop the experiment at any time, if he felt
uncomfortable during the experiment. The study was approved by the local ethics
committee.

2.2. Stimulation and pain rating

Electrical stimulations (0.2ms square wave pulse, 1.9Hz) were applied to thumb
(Digit-1, D1) and little finger (Digit-5, D5), respectively by the pin-electroded, i.e.
fastened on a Velcro-ring device with a sharp pin induced clear and distinct
pricking sensation at the fingertip. The pain intensity Verbal Rating Scaling
system-VRS was introduced to subject prior to carrying out the experiment. The
subject was familiarized with the VRS system and asked to report a number
according to the psychophysical feeling when the intensity of the stimulus
varying.


The pain intensity was rated on a 0-10 verbal rating scale (VRS) defined as
follows: (0) No change, (1) Barely Intense, no pain, (2) Intense, no pain, (3) Fairly
Intense, but no pain, (4) Slight Pain (Pain Threshold), (5) Mild Pain, (6) Moderate
Pain, (7) Moderate-Strong Pain, (8) Strong Pain, (9) Severe Pain, (10)
Unbearable Pain.
In order to define the no-painful and painful intensities of the stimulation for each
subject, a procedure for stimulation intensity verification should be conducted
before the experiment. The intensities for four conditions (D1: Non-pain, D1:
Pain, D5: Non-pain, D5: Pain) were recorded five times by the Method of
Ascending Limit, separately and the mean value was used as the stimulation
intensity for each condition according to subjective rating of intense for non-pain
(intensity-2) or moderate Pain (intensity-6).

2.3. EEG Recording procedure

The intensities of Stimulation1 and Stimulation2 are randomized by high intensity
(intensity-5) or low intensity (intensity-2).

                      Stimulation 1                      Stimulation 2

    D1 and D5 (I-6)                    D1 and D5 (I-6)                   D1 and D5 (I-6)


    SEP (BS)                           SEP 1 (AS1)                        SEP (AS2)



                           Fig.1 The protocal of experiment
Each subject sat comfortably in a chair throughout the experiment in a quiet room
(temperature at 20-22°C). The head circumference of the subject, and the
distance between the nasion and inion were measured. A suitable electro-cap
was then used to record the EEG. The first electrode Fpz was 2 cm far from the
nasion, and the Cz was located at the junction, halfway between the ears and the
middle of the nasion and inion, when the cap was placed on the head. The
ground electrode was placed, half way between the eyebrows. Electrodes M1
and M2 were placed on bilateral mastoids and were used as the reference
channels. Subjects kept their eyes-open and fixed their gaze at a point on the
wall during the experiment.
The subjects were instructed to be alert to the sensation induced at the
stimulated site, overly count the stimuli and fully relaxed. A total of 300 trials for
each condition were gathered. EEG recordings were carried out using 128-
Channels high density A.N.T. System (0.1-7000Hz bandpass, 2048 sampling
frequency rate), including two electro-oculogram (EOG) channels and two
reference channels M1 and M2. Ag/AgCl electrodes (5 mm diameter) were
attached to the scalp using electrode cream (EC2, Grass), and the electrodes
impedances were kept lower than 10 kΩ. The electrodes were mounted
according to the montage 10-5 system (Oostenveld and Praamstra, 2001).
There was a 15 min. transcutaneous electrical acupoint stimulation between
each SEP recording condition at 100Hz. The order of the stimulus intensities was
randomised in between individual subjects.

2.4. EEG Data Management

EEG was recorded on-line with reference to the unilateral left mastoid (M1).
Bilateral EOG was recorded from the horizontal and vertical sites monitored
blinking or eye movements, and the eyes movement artefacts were rejected in
the off-line analysis. At off-line processing, the 124-ch EEG channels were re-
referenced versus the bilateral reference (averaged M1 and M2) and processed
by band-pass filtering 0.5-100hz, notch filtering 50 Hz. Fifty milliseconds of pre-
stimulus and 450ms of post-stimulus was recorded as one epoch, then these
epochs were conducted to linear-detrend and artefact rejection processing (e.g.
an overview visual inspection bad electrodes combining epoch by epoch visual
inspection). The artefact rejection methods consisted of excluding epochs with
large amplitude (exceed ±80 V), DC bias, blinking, and slow eye movement
coincident with EOG. After rejection of EOG contamination and non-specific
artefacts, each set of EEG data (500ms epoch) was subjected to averaging for
each finger in each subject. All electrodes were inspected and bad electrodes
were then interpolated from the neighborhood electrodes with the virtue values.
Some of them, which cannot be fixed, were removed. A grand average was
obtained from the ten subjects in the group. All these data processing procedures
were carried out by EEprobe program (A.N.T. Nehterlands). Then the further
analysis was carried out by ASA3.0, some specific peak stages of SEP were
extracted according to the compressed waveform of 124 channels. The related
topography and dipole fit analysis of distinct specific peak stage at different
conditions were processed. The event for each peak stage was defined, and the
duration of the event was defined 4ms for early peak stages and 10ms for late
peak stages, respectively according to the their features, i.e. the early peak
stages, the activation were sharp and narrow, the late peak stage, the activation
was more blunt and broad. Then a moving dipole model was used to calculate
the dipole for each peak stage. The related parameters of the dipole, e.g.
position, magnitude, were investigated for the further analysis.

2.5. Statistical Analysis

The activities of human brain before and after stimulation were studied using
dipole fit analysis across four conditions. Due to the middle latency is transient
stage, and the variability of this stage was very big and unstable among the
subjects. Only two early peak stages and two late peak stages were analyzed for
each condition, i.e. D1/AS, D1/BS, D5/AS, and D5/BS were analyzed.
Two-way RM ANOVA (two-way repeated measures ANOVA) was used to
investigate the effects from BS to AS on focal amplitude (FA) and area
magnitude (AM), and also on D1 and D5 by using statistical software
SigmaStat2.03. Two factors were conditions (AS vs. BS) and digits (D1 vs. D5).
Tukey-test was also used for post-hoc pair-wise multiple comparison of the
means from the ANOVA analysis. Paired t-test was conducted to investigate the
significant change of dipolar positions, and dipolar magnitudes at four peak
stages from BS to AS. Significant statistical level was set as P<0.05.
3. Results

3.1. Waveform of D1 and D5 over Baseline and Post-stimulation
According to compressed waveform of the group at four conditional stimulations,
BS/D1, BS/D5, AS/D1, AS/D5, related distinct peak stages were extracted and
labeled as shown in Fig.2. Only the peak stages in the early and the late phases
were labeled and extracted since the great variability among individual subjects
exists in the middle phase. Two peak stages were selected for each phase.
BS/D1 (34ms, 45ms, 212ms, 331ms), BS/D5 (36ms, 46ms, 226ms, 350ms),
AS/D1 (38ms, 47ms, 208ms, 368ms), and AS/D5 (36ms, 49ms, 224ms, 344ms).

                              D1                                      D5

                                           382                                   350
        -                           331                -                   325




  BS

             34                                            36 46
                  45               212
                        162                                          197         226
        +                                              +

                                                                                             344
                                   368
         -                                             -


  AS

                                                           36
             38                                                 49
                   47                     208
        +                                              +                               224



Fig.2 The compressed waveform of group (n=10) before stimulation (BS) and
after stimulation (AS) for D1 and D5 Each response has been filtered with band
pass filter 0.5-100Hz, and notch filter 50Hz. The black straight line is the onset of
the stimulation, and the sensitivity of these figures is 1μV/cm.
Results indicated that the response activation of D5 has higher amplitudes at four
peak stages than that of D1, especially in the late phase.
3.2 . The comparison of topography before stimulation (BS) and After Stimulation
   (AS) on D1and D5
The amplitude of focal maximal at each peak stages was increased obviously
except at 36 ms of D5 after high intensity stimulation, and the area size of
activation were also extended from the central parietal to bilateral as well,
especially at the late peak stages. At the early peak stages, the contralateral
sites corresponding to the stimulation position right D1 and D5, appeared
outstanding activities from 33ms to 44 ms, and at the late phase, the activities
consistently concentrated on cortical vertex.

                 34ms              45ms               212ms             331ms




  BS/D1




  AS/D1




                36ms                46ms               226ms            350ms




  BS/D5




  AS/D5
Fig.3 The topography of four peak stages for each conditions, high intensity
stimulation applied to the right thumb (D1) and right little finger (D5). All
topographies were displayed with the automatic scale to emphasize the spatial
activities.


3.3 . Effect of Stimulation Intensity on SEPs of D1 and D5
The effect of the stimulation on the scalp amplitude was analyzed with two-way
RM ANOVA (condition, BS vs. AS, and digit, D1 vs. D5). SEPs were significantly
affected by the transcutaneous electrical stimulation, and the effects were
different between the early and late phases. Fig. 4 showed the effects of low and
high intensity stimulations on D1, Fig.5 showed the effects of low and high
intensity stimulations on D5. The early activities were mainly affected by the
intensities of stimulation, the early positive activities of the response were
significant increased at 35 ms (FA: p=0.016, AM: p=0.004), and decreased at 45
ms (FA: p<0.001, AM: p=0.001) after high intensity stimulation on D1, but no
effect on D5. However, there was no significant effect with the low intensity
stimulation on both D1 and D5. In contrast, both high and low stimulation
intensity showed the similar effects on the amplitudes of the late negative
activities in SEPs, which were significant increased at 350 ms, on the response
of D5 (for I5, FA:p<0.001, AM: p=0.002; for I1, FA: p=0.002, AM: p=0.004), but
no D1. Furthermore, there was no significant difference between positive
responses of D1 and D5 before stimulation, after high intensity stimulation, the
amplitude of positive response of D1 is significant bigger than that of D5 at 33 ms
(FA: p=0.008, AM: p<0.004). It implied that transcutaneous electrical stimulation
resulted in different effects on early activities and late activities in SEP responses
of D1 and D5, and resulted in the different influence in primary somatosensory.
                         Low-intensity stimulation                                     High-intensity stimulation

                                  Focal Amplitude                                                Focal Amplitude
                                                                BS                                                             BS
                8                                                             8
                6                                               AS                                                             AS
                                                                              6
                4                                                             4
                2                                                             2
FA/D1
        (μV)




                                                                      (μV)
                0                                                             0
               -2                                                            -2
               -4                                                            -4
               -6                                                            -6
               -8                                                            -8
                        36ms   36ms   48ms    48ms    226ms   352ms                   34ms    34ms   45ms    45ms    212ms   331ms
                                       Peak Stage                                                     Peak Stage

                                  Area Magnitude                                                 Area Magnitude
                                                                BS                                                              BS
               30                                                             30
                                                                AS                                                              AS
               20                                                             20
AM/D1          10                                                             10
        (μV)




                                                                      (μV)
                    0                                                             0
               -10                                                           -10
               -20                                                           -20
               -30                                                           -30
                        36ms   36ms   48ms     48ms   226ms   352ms                    34ms   34ms   45ms     45ms   212ms   331ms
                                        Peak Stage                                                     Peak Stage




         Fig. 4 The comparison of the scalp potential amplitude before stimulation (BS)
         and after low (I-1) and high-intensity (I-5) stimulations (AS) on D1 over group
         (n=10) Focal maximum Amplitude (FA, single central site at 0.2 cm2) and Area
         Magnitude (AM, summated FA and amplitudes of neighboring four sites in a
         region of nearly 9.9 cm2 area) were used to exam the change, where, ‘*’ indicates
         significant change p<0.05, ‘**’ indicates significant change p<0.01, ‘***’ indicates
         significant change p<0.001.
                         Low-intensity stimulation                                       High-intensity stimulation

                                Focal Amplitude                                               Focal Amplitude
                                                              BS                                                            BS
                 8                                                           8
                 6                                            AS             6                                              AS
                 4                                                           4
                 2                                                           2
         (μV)




                                                                    (μV)
                 0                                                           0
FA/D5           -2                                                          -2
                -4                                                          -4
                -6                                                          -6
                -8                                                          -8
                      35ms   35ms   47ms    47ms    224ms   340ms                 36ms     36ms    46ms   46ms    226ms   350ms
                                      Peak Stage                                                    Peak Stage


                                Area Magnitude                                                Area Magnitude
                                                              BS                                                            BS
                 40                                                          40
                                                              AS                                                            AS
                 30                                                          30
AM/D5            20                                                          20
                 10                                                          10
        (μV)




                                                                     (μV)




                  0                                                           0
                -10                                                         -10
                -20                                                         -20
                -30                                                         -30
                -40                                                         -40
                      35ms   35ms   47ms     47ms   224ms   340ms                  36ms     36ms   46ms    46ms   226ms   350ms
                                      Peak Stage                                                    Peak Stage




        Fig.5 The change of the scalp potential amplitude before stimulation (BS) and
        after low (I-1) and high-intensity (I-5) stimulation (AS) on D5 over group (n=10)
        Focal maximum Amplitude (FA, single central site at 0.2 cm2) and Area
        Magnitude (AM, summated FA and amplitudes of neighboring four sites in a
        region of nearly 9.9 cm2 area) were used to exam the change, where, ‘*’ indicates
        significant change p<0.05, ‘**’ indicates significant change p<0.01, ‘***’ indicates
        significant change p<0.001.
3.4. Locations of dipole before and after stimulation
In order to analyze the influence of transcutaneous electrical stimulation on SEPs
of D1 and D5, dipole analysis was carried out. It was well known that the
activities of primary somatosensory area corresponding to the stimulation site
elicited was related to the early activities of SEP, hence high intensity
stimulations, which can result in the significant change to early activities of SEP
on D1 and have the similar influence for the late activities comparing with low
intensity stimulation, was studied by dipole analysis. Because the great individual
difference and the resolution restriction of dipoles analysis method, only grand
average file across group (n=10) was shown in Fig.6 (for D1) and Fig.7 (for D5),
which can provide a general description on the effects of stimulation. At AS, the
locations of the source were deep, and it closed to lateral at the early stages, but
closed to median at 331 ms comparing with BS see Fig.6. in contrast, for D5, at
AS, the locations of the source were shallow, and it closed to midline compared
with BS.
   34ms




   45ms




 212ms




 331ms




Fig.6 The changes of the dipole position before stimulation (BS) and after high
intensity stimulation (AS) for D1 at four peak stages. The green dot indicates BS,
the red one indicates AS.
   36ms




   46ms




 226ms




 350ms




Fig.7 The changes of the dipole position before stimulation (BS) and after high
intensity stimulation (AS) for D5 at four peak stages. The green dot indicates BS,
the red one indicates AS.
     3.5. Changes of dipole on 33ms before and after stimulation for D1 and D5
     Paired t-test was used to compare the locations in the early activities of SEPs
     with dipolar parameters, i.e. the coordinates of x, y, and z-axis of dipoles
     between BS and AS. Statistical results showed that the location of dipole at 33ms
     there was significantly ascended to the cerebral parietal, but the magnitude of
     dipole was significant decreased after high intensity stimulation on D5. However,
     the activities of D1 did not show significant change even the activities explored
     the different tendency, i.e. the dipolar location sank, and the magnitude
     increased.



                          Position                                      Magnitude

            80                                                     80
            60
                                                                   60
            40
D1                                                  BS                                   BS
     (mm)




            20                                             (nAm)   40
                                                    AS                                   AS
              0
                                                                   20
            -20
            -40                                                     0
                  x           y           z                             Magnitude


                          Position                                      Magnitude

            80                                                     60
            60
                                                                   45
            40
D5                                                  BS                                   BS
     (mm)




                                                           (nAm)




            20                                                     30
                                                    AS                                   AS
              0
                                                                   15
            -20
            -40                                                     0
                  x           y           z                             Magnitude




     Fig. 8 The changes of dipole on 33ms before and after stimulation (BS and AS)
     for D1 and D5 x, y, and z are the coordinates of the dipole, the magnitude is
     dipolar magnitude, where, ‘*’ indicates significant change p<0.05.
3.6. Effect of Stimulation on the Euclidian distance Between D1 and D5
The Euclidian distances between D1 and D5 were also analyzed before and after
stimulations (BS and AS). Due to the great individual difference, the distance of
D1 and D5 was calculated according to the dipolar loci for the grand averages of
the SEPs under BS and AS, the distance of D1 and D5 at the different peak
stages were shown in Fig. 9. The distance seems decreased after high intensity
stimulation compared with BS except at 331 ms. It indicated the activities of the
responses become more clear and concentrated after stimulation on D1 and D5
and has the tendency to decrease the distance between D1 and D5.


                                     Distance of D1 and D5

                         25
                         20
         Distance (mm)




                         15                                              BS
                         10                                              AS

                          5
                          0
                              38ms      45ms       212ms     331ms
                                           Peak Stage




Fig. 9 Effect of Stimulation on the Euclidian distance Between D1 and D5
4. Discuss




4.1. Significance of the early activities in SEPs
The aim of the present study was to examine if the stimulation intensity of high-
frequency (100 Hz) repetitive conditioning transcutaneous electrical stimulation
induced in the different effects on the SEPs of D1 and D5 and whether or not the
high intensity stimulation can induce in the change of cortical plasticity in humans
e.g. the distance of D1 and D5 in SEP response. The primary somatosensory
cortex has well been described by recent decades studies, cortical receptive field
properties can be reorganized, rapid, and dynamic changed with some selective
visual stimulation, injury, or peripheral stimulation. Recently, the map
representing parts of the body has been testified that, it can be pliable in adult
mammals and changed in response to experience and injury. E.g. the amputation
of a finger, the respective absent-finger part in cortical was occupied by the
adjacent area which represent the other parts of the body. Due to the early
activities are in response to the activities of receptive field at the primary
somatosensory (S1) cortex, which represents the parts of the body at the
anatomical location in the cortex. Hence, when D1 and D5 elicited by the
tanscutaneous electrical stimulation, the site of the firing at the cortex could be
found, the change occurred after painful stimulation could provide the significant
information of the cortical plasticity changing, it might be useful to provide some
reference for modification of cortical activity might become an effective tool in
pain management.


4.2. Spatial extent of SEPs in relation to different intensity stimulations
4.3. Effect of high intensity stimulation on dipolar parameter


Since the locations of the dipole generator caused by different intensity
stimulations are different, it might imply that the pain perception generator can be
modulated by the intensity of the stimulations.




4.4. Euclidian distance of D1 and D5 and cortical plasticity


Amplitude change-cortical plasticity.
(1) the amplitude of SEP can be affected by different afferent agent, state of
arousal on pain-related SEP (sleep) (a), CO2 Laser transcutaneous electrical
nerve stimulations, attention, distraction tasks (calculation, or memorization) ,
and execution of motor task (movement) etc. the decreased amplitude and
prolonged latency of early cortical potentials were reported.


(2) In transcutaneous electrical nerve stimulations, stimuli parameters (frequency
(H/L), Intensity(H/L), ISI (randomized /fixed), experiment sites (hand, median
nerve, digits), the results are differents.
(3) Early component and Late component of response conducted by different
fibers, it has been concluded that the early component activated by signals
ascending through fast A-beta fibers (50-70 m/s) relating to touch and late
component activated by signals ascending through slow A-delta fibers (10-15
m/s) relating to pain.


Some studies showed the N60 was much reduced in amplitude during sleep, it
was speculated that it close related to the cognitive function, which as the start
responded the pain stimulation, while the early component , generated in SI
which almost without any effect from the different modulation, which is mainly
related the A-Beta. Consider all these modulation methods, it concluded that in
order to relief the pain sensitivity , the more effective method is to block the A-
delta nerve conduction, then the pain gating will be changed, the amplitude and
latency will be modulated. Because the early component related the touch sense,
which also projected the mapping part in primary somatosensory cortex SI, can
be used to identity the position of the site. The late component (after 100 ms )
didn’t reflect the position of the sitmulation site, but intensity of the pain. Painful
electrical stimulation activates both A-beta and A-Delta fibers. In general the
amplitude of SEP is smaller than that of median nerve for early component, it
because the different activated nerve numbers result in the different results.


Location/position change -> cortical plasticity.




Influence factors for cortical plasticity




We report experiments in which we investigated the reorganizational capacities
in primary somatosenory cortex before and after a transcutaneous electrical
nerve stimulations on thumb and little finger by means of somatosensory evoked
potentials (SEPs) mapping and ECD dipole locations.


Results imply that the transcutaneous electrical nerve stimulation leads to the
reorganized in S-I, especially on vertical direction, while the other two direction
without significant change. But the distance between thumb and littler finger has
a tendency of decrease.


The extent of cortical reorganization depends in part on the characteristics of the
stimulus statistics has been testified by such research groups XXXXXXX, training
and learning can enlarge the in the cortical representational areas, and the
immobilization will decrease the representation areas in cortex.


The effects of transcutaneous nerve stimulation on the late somatosensory
evoked potentials (SEPs) have been investigated by stimulate median nerve
(Ashton, 1984) at moderate, non-painful intensity, the peak-to-peak amplitude of
the late components reduced occurred at N1 around 100-160 ms, and P2 around
160-260 ms. also the latency increased for N1

Introduction

plasticity change, can be investigated by different techniques, positron emission
tomography (PET), functional magnetic resonance imaging (fMRI),
magnetoencephalography (MEG), and electroencephalography (EEG), depending on the
experimental purpose. The EEG with good temporal advantage is used for investigate our
present study, in some animal models, the organization of primary somatosensory cortex
can be changed by the some external agents, e.g. perpheral nerve stimulation
(XXX,XXX) or the acute and chronic pains, as well as in humans (XXXX). The different
stimuli, laser, transcutaneous electrical stimuli, and heat and cold stimulation were used
to elicit the peripheral nerve. The effects of these stimulations were investigated. In these
stimulations, the transcutaneous electrical stimuli were extensively applied to clinics and
researches in the past several decades to be an inhibition method of pain.




The parameters of the stimulations
Transcutaneous electrical nerve stimulation (TENS) has been applied extensive clinics as
an analgesia method to release the pain in mammals, e.g. renal pain in cats ( Nam et al.,
1995),

Cortical plasticity can be modulated and re-organized by different agents, e.g. some
functional recovery movements (XXX), cognitions (XXX), training and memory (XXX),
or some stimulation (XXX). It has extensively been investigated across species in human
and other animals. The related study of the cortical stimulation, which can modulate the
cortical plasticity, could enhance the understanding of mechanisms and function the
plasticity.

Our present study aimed at the cortical plasticity change after a repetitive conditioning
transcutaneous electrical stimulation on hand. The cortical SEP component change before
and after TENS was investigated by EEG and dipole analysis. Previous studies (XXXX)
has demonstrated the different effects with low (4 Hz) and High (100 Hz) stimulation
frequencies, more effective efficacy of the high stimultion frequency has also been
extensively proved by number experiments (XXXX, XXXX, XXX). Hence, the high
frequency 100 Hz was applied to the stimulation in the present study.

The results in the present study showed the effects of TENS on the primary
somatosensory cortex, the dynamic pattern in SEP response before stimulation (BS) and
after stimulation (AS) kept consistent for both D1 and D5 see fig.1, fig.2, the amplitude
of SEPs increased obviously, in the early activities, the amplitudes of SEPs for D1 at 34
ms (increased) and 45 ms (decreased) changed oppositely at AS comparing with BS see
fig.3. In contrast, for D5, the early activities decreased with the same tendency at 36 ms
and 46 ms but without significant change. As for the late activities, the amplitude of SEPs
increased, but no significant change on D1. However, the amplitude of SEPs of D5
showed significant increased at 350 ms. The results suggested that cortical responses of
D1 and D5 could be modulated by TENS, and the stimulation signals on peripherial
nerves might ascending through the different nerves clusters, which resulted in the
different response changes of SEPs in cortex. The activities of the response




: J Pain. 2003 Apr;4(3):109-21.                                         Related Articles, Links



       Transcutaneous electrical nerve stimulation: basic science
       mechanisms and clinical effectiveness.

       Sluka KA, Walsh D.
      Physical Therapy and Rehabilitation Sciences Graduate Program, Neuroscience
      Graduate Program, Pain Research Program, University of Iowa, Iowa City, IA
      52242, USA. kathleen-sluka@uiowa.edu

      Transcutaneous electrical nerve stimulation (TENS) is used clinically by a variety
      of health care professionals for the reduction of pain. Clinical effectiveness of
      TENS is controversial, with some studies supporting whereas others refute its
      clinical use. Although used by health professionals for decades, the mechanisms
      by which TENS produces analgesia or reduces pain are only recently being
      elucidated. This article describes the basic science mechanisms behind different
      frequencies of TENS stimulation. Specifically, we describe the literature that
      supports the use of different frequencies and intensities of TENS. We further
      describe theories that support the use of TENS such as the gate control theory and
      the release of endogenous opioids. The literature that supports or refutes each of
      these theories is described. We also review the clinical literature on TENS
      effectiveness and elucidate the problems with clinical research studies to date. In
      conclusion, TENS is a noninvasive modality that is easy to apply with relatively
      few contraindications. However, the clinical efficacy of TENS will remain
      equivocal until the publication of sufficient numbers of high quality, randomized,
      controlled clinical trials.

      Publication Types:

             Review
             Review, Academic


      PMID: 14622708 [PubMed - indexed for MEDLINE]


: Cochrane Database Syst Rev. 2003(3):CD004287.                       Related Articles, Links


      Update in:

             Cochrane Database Syst Rev. 2004;(2):CD004287.


      Transcutaneous electrical nerve stimulation (TENS) for the
      treatment of rheumatoid arthritis in the hand.

      Brosseau L, Yonge KA, Robinson V, Marchand S, Judd M, Wells G, Tugwell
      P.

      School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road,
      Ottawa, Ontario, Canada, K1H 8M5.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, system
disease. It commonly affects the small peripheral joints (such as fingers and
wrist). The main goals of intervention for RA are preventing joint deformity,
preserving joint function, and reducing inflammation and pain. Transelectrical
nerve stimulation (TENS) is a form of electrotherapy and is thought to produce
analgesia according to the gate control theory. OBJECTIVES: To determine the
efficacy and safety of TENS in the treatment of RA of the hand. The primary
outcomes of interest were relief of grip pain and resting pain intensity, relief of
joint tenderness, number of tender joints and patient assessment of disease. The
secondary objective was to determine the most effective mode of TENS
application in pain control. SEARCH STRATEGY: We searched for relevant
studies, in English, in the Cochrane field of physical and related therapies, the
Cochrane Controlled Trials Register, MEDLINE, EMBASE, HEALTHSTAR,
Sports Discus, CINAHL, Current Contents, and the PEDro database, up to
October 2002. SELECTION CRITERIA: Two independent reviewers selected the
trials that met predetermined inclusion criteria. DATA COLLECTION AND
ANALYSIS: Study results were extracted by two independent reviewers.
Continuous outcomes were analyzed by weighted mean difference (WMD) using
a fixed effects model. MAIN RESULTS: Three RCTs, involving 78 people, were
included in this review. AL-TENS and C-TENS were compared to placebo and to
each other. Administration of 15 minutes of AL-TENS a week, for 3 weeks,
resulted in a significant decrease in rest pain (67% relative benefit, 45 points
absolute benefit on 100 mm VAS scale) but not in grip pain compared to placebo.
AL-TENS did result in a clinical beneficial improvement in muscle power scores
with a relative difference of 55%, and an absolute benefit of 0.98, compared to
placebo. No significant difference was found between one 20-minute treatment
duration of C-TENS versus AL-TENS, or C-TENS versus placebo on decrease in
mean scores for rest pain or grip pain, or on the number of tender joints. Results
showed a statistically significant reduction in joint tenderness, but no clinical
benefit from C-TENS over placebo in relief of joint tenderness. No statistically
significant difference was shown between 15 days of treatment with C-TENS or
AL-TENS in relief of joint pain, although there was a clinically important benefit
of C-TENS over AL-TENS on patient assessment of change in disease (risk
difference 21%, NNT 5). REVIEWER'S CONCLUSIONS: There are conflicting
effects of TENS on pain outcomes in patients with RA. AL-TENS is beneficial
for reducing pain intensity and improving muscle power scores over placebo
while, conversely, C-TENS resulted in no clinical benefit on pain intensity
compared with placebo. However C-TENS resulted in a clinical benefit on patient
assessment of change in disease over AL-TENS. More well designed studies with
a standardized protocol and adequate number of subjects are needed to fully
conclude the effect of C-TENS and AL-TENS in the treatment of RA of the hand.

Publication Types:

      Review
             Review, Academic


      PMID: 12918009 [PubMed - indexed for MEDLINE]

1: J Pharmacol Exp Ther. 1999 May;289(2):840-6.                           Related Articles, Links




      Spinal blockade of opioid receptors prevents the analgesia produced
      by TENS in arthritic rats.

      Sluka KA, Deacon M, Stibal A, Strissel S, Terpstra A.

      Neuroscience Graduate Program, The University of Iowa, Iowa City, Iowa,USA.
      kathleen-sluka@uiowa.edu

      Transcutaneous electrical nerve stimulation (TENS) is commonly used for relief
      of pain. The literature on the clinical application of TENS is extensive. However,
      surprisingly few reports have addressed the neurophysiological basis for the
      actions of TENS. The gate control theory of pain is typically used to explain the
      actions of high-frequency TENS, whereas, low-frequency TENS is typically
      explained by release of endogenous opioids. The current study investigated the
      role of mu, delta, and kappa opioid receptors in antihyperalgesia produced by
      low- and high-frequency TENS by using an animal model of inflammation.
      Antagonists to mu (naloxone), delta (naltrinodole), or kappa (nor-
      binaltorphimine) opioid receptors were delivered to the spinal cord by
      microdialysis. Joint inflammation was induced by injection of kaolin and
      carrageenan into the knee-joint cavity. Withdrawal latency to heat was assessed
      before inflammation, during inflammation, after drug (or artificial cerebral spinal
      fluid as a control) administration, and after drug (or artificial cerebral spinal fluid)
      administration + TENS. Either high- (100 Hz) or low- frequency (4 Hz) TENS
      produced approximately 100% inhibition of hyperalgesia. Low doses of naloxone,
      selective for mu opioid receptors, blocked the antihyperalgesia produced by low-
      frequency TENS. High doses of naloxone, which also block delta and kappa
      opioid receptors, prevented the antihyperalgesia produced by high-frequency
      TENS. Spinal blockade of delta opioid receptors dose-dependently prevented the
      antihyperalgesia produced by high-frequency TENS. In contrast, blockade of
      kappa opioid receptors had no effect on the antihyperalgesia produced by either
      low- or high-frequency TENS. Thus, low-frequency TENS produces
      antihyperalgesia through mu opioid receptors and high-frequency TENS produces
      antihyperalgesia through delta opioid receptors in the spinal cord.

        PMID: 10215661 [PubMed - indexed for MEDLINE]
1: Clin Exp Obstet Gynecol. 1997;24(3):123-6.                             Related Articles, Links


      Transcutaneous electrical nerve stimulation (TENS) as a pain-relief
      device in obstetrics and gynecology.

      Kaplan B, Rabinerson D, Pardo J, Krieser RU, Neri A.

      Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva,
      Israel.

      Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological and
      non-invasive pain-relief method that has been proven effective for a variety of
      conditions. Electrical therapy has been recognized for a long time but its practical
      clinical application in the form of TENS has been evaluated only during the last
      30 years as a result of several theories on pain. The most known of these with
      regard to TENS development is the "gate theory", although several others have
      also played a role. In obstetrics and gynecology, TENS has been found to be
      effective in alleviating labor pain and in the treatment of primary dysmenorrhea.
      It has also been used successfully following obstetric and gynecologic surgery. In
      order to be effective in clinical use for obstetric and gynecologic indications, a
      TENS device must have certain properties, which are detailed in this review.
      Although new TENS devices that meet all the necessary requirements have been
      developed and tested, their use is still far from widespread. Patients and medical
      staff should be encouraged to try the TENS device for obstetric and gynecologic
      indications, since it is non-invasive, efficient, and easy to use.

      Publication Types:

             Review
             Review, Tutorial


       PMID: 9478293 [PubMed - indexed for MEDLINE]
1: Minerva Stomatol. 1995 Sep;44(9):421-9.                             Related Articles, Links


      [Highlights in the subject of low frequency-high intensity TENS
      (review)]

      [Article in Italian]

      Galletti SP, Bergamini M, Pantaleo T.

      Istituto di Odontognatostomatologia, Universita degli Studi, Firenze.

      Transcutaneous electrical neural stimulation (l.f.-h.i. TENS), employed in
      dentistry, allows masticatory muscles relaxation, temporary clearance of muscular
      and periodontal proprioceptive input and even oro-facial pain relief. The
      mechanisms involved in this type of stimulation are not entirely clarified.
      According to the most recent neurophysiological researches, the authors describe
      several l.f.-h.i. TENS. action modalities. Some of them are well known such as
      the gate control theory, the endogenous antinociceptive system activation, the
      metabolic recovery of the muscular tissue and the unloading reflex. Other
      mechanisms, instead, are less known such as hypnosis and stress analgesia,
      exteroceptive suppression and counterirritation (DNIC). Some hypothetical
      mechanisms are also considered such as endogenous inhibition and sympathetic
      activity reduction.

      Publication Types:

             Review
             Review Literature


        PMID: 8668116 [PubMed - indexed for MEDLINE]
1: Pain. 1994 Sep;58(3):309-15.                                      Related Articles, Links


      Decreased activity of spontaneous and noxiously evoked dorsal horn
      cells during transcutaneous electrical nerve stimulation (TENS).

      Garrison DW, Foreman RD.

      Department of Physical Therapy, University of Oklahoma Health Sciences
      Center, Oklahoma City 73190.

      The purpose of this study was to examine the effects of TENS application to
      somatic receptive fields on spontaneous and noxiously evoked dorsal horn cell
      activity in alpha-chloralose-anesthetized cat. Carbon-filament microelectrodes
      were used to record extracellular action potentials from 83 spontaneously
      discharging cells. Using a commercial TENS unit (Medtronic Eclipse Model
      7723), spontaneous cell activity was decreased in 54% (65%) of the cells.
      Twenty-five (30%) did not respond and 4 (5%) increased activity. It was also
      shown that for 36 cells which were evoked with either manual pinch (19 cells) or
      manual clamp (17 cells), cell activity decreased during TENS application. This
      study shows that dorsal horn neurons which can potentially transmit noxious
      information to supraspinal levels, can have their cell activity decreased during
      TENS application to somatic receptive fields. This is consistent with the concept
      of the 'gate control theory of pain' in that less noxious information would be
      involved in the pain perception process.

      PMID: 7838579 [PubMed - indexed for MEDLINE]

1: Psychosom Med. 1979 Mar;41(2):101-8.                              Related Articles, Links


      A signal detection analysis of the effects of transcutaneous
      stimulation on pain.
       Malow RM, Dougher MJ.

       Transcutaneous nerve stimulation (TNS) applied both ipsilaterally and
       contralaterally with a tonic pain stimulus was compared to a control condition to
       determine its effect on pain reports. The ipsilateral TNS condition significantly
       reduced ratings and increased pain thresholds relative to the contralateral and
       control conditions which did not significantly differ from each other. A Signal
       Detection Theory analysis of the data was employed to assess the sensitivity and
       response bias effects of the treatment conditions. Ipsilateral TNS significantly
       reduced pain sensitivity and response bias in the direction of showing a lesser
       tendency to report pain. The effects of ipsilateral TNS were most pronounced at
       the higher levels of stimulation. The results are consistent with Gate Control
       Theory which holds that ipsilateral TNS attenuates painful sensation. Most
       importantly, these results support the efficacy of TNS for the treatment of clinical
       pain.
1: Phys Ther. 1978 Dec;58(12):1443-9.                                    Related Articles, Links


       Perspectives on central nervous system responsiveness to
       transcutaneous electrical nerve stimulation.

       Wolf SL.

       This review article is designed to further enlighten the physical therapist about
       pathways transmitting nociceptive information and about systems capable of
       inhibiting this transmission. At present, little information exists to explain how
       transcutaneous electrical nerve stimulation effects changes in pain perception.
       Contemporary knowledge regarding proposed modes of action for this modality is
       presented in light of current neurophysiological information. In explaining the
       action of transcutaneous electrical nerve stimulation, alternatives to the gate-
       control theory of pain are suggested as being quite possible. Questions regarding
       future investigations are proposed.

       PMID: 217027 [PubMed - indexed for MEDLINE]
1: J Neurol. 1977 Dec 1;217(1):1-10.                                        Related Articles, Links


       Influence of transcutaneous nerve stimulation (TNS) on acute pain.

       Strassburg HM, Krainick JU, Thoden U.

       Using transcutaneous nerve stimulation (TNS) simple surgical procedures such as
       tooth extractions and nerve biopsies can be performed without the usual
       anesthetics. Estimation of threshold and suprathreshold intensities of painful
       electrical stimuli show no significant change during TNS. Only the threshold for
       non-painful electrical stimuli is slightly increased. Cortical potentials evoked by
       electrical peripheral nerve stimulation are not significantly modulated by TNS.
       Latencies of the early components 0, I--III are unchanged, the amplitudes only
       slightly reduced. These observations are in contradiction to the 'gate-control'
       theory of pain.

        PMID: 75247 [PubMed - indexed for MEDLINE]
1: Clin Orthop. 1977 Oct(128):314-24.                                    Related Articles, Links


       Transcutaneous electrical neurostimulation: a new therapeutic
       modality for controlling pain.

       Ersek RA.

       Transcutaneous electrical neurostimulation relieves chronic and acute pain by
       blocking the transmission of pain impulses with comfortable electrical stimulation
       of light touch sensation. The original Gate Control Theory of Melzack and Wall
       provides a working model to explain the significant pain relief afforded patients.
       As high as 80% of selected patients presenting with a wide variety of causes could
       achieve some relief after treatment. This comfortable, safe method is finding wide
       application in clinical practice.

       PMID: 145920 [PubMed - indexed for MEDLINE]
1: Anaesthesist. 1976 May;25(5):204-7.                                   Related Articles, Links


       [Acupuncture and pain mechanisms (author's transl)]

       [Article in German]

       Melzack R.

       Three modulating mechanisms of the "gate-control theory" provide a plausible
       explanation of how acupuncture analgesia works. In particular, the inhibitory
       effects of the brainstem reticular formation on the transmission of pain signals in
       the spinal cord or at higher ttransmission levels seems to provide a powerful
       explanatory concept. Intense stimulation through acupuncture needles could
       activate this inhibitory brainstem system, thereby closing the gate to pain signals.

       Publication Types:

             Review


       PMID: 183560 [PubMed - indexed for MEDLINE]

1: Brain Topogr. 2002 Winter;15(2):95-106.                               Related Articles, Links


       Reliability and validity of neuroelectric source imaging in primary
     somatosensory cortex of human upper limb amputees.

     Schaefer M, Muhlnickel W, Grusser SM, Flor H.

     Department of Clinical and Cognitive Neuroscience at the University of
     Heidelberg, Central Institute of Mental Health, Mannheim, Germany.
     mischa@neuro2.med.uni-magdeburg.de

     The present study investigated the test-retest reliability of EEG source
     localizations of somatosensory evoked potentials (SEPs) in human upper limb
     amputees over a long time frame (several months) and examined the validity of
     source reconstruction. In two sessions spaced several months apart five unilateral
     upper limb amputees were stimulated at the first and fifth digit of the intact hand
     and at the left and right lower corner of the mouth. To examine the validity of the
     results of the neuroelectric source reconstruction a comparison with
     neuromagnetic source localization was performed for two subjects. The source
     localizations of the SEP components were found to be highly reproducible: the
     mean standard deviation of the dipole locations was 8.80 mm in the x-, 7.00 mm
     in the y- and 4.15 mm in the z-direction. The match of the comparison of EEG
     and MEG data was in the range of one centimeter. These results support the use of
     multi-electrode EEG recordings combined with MRI as an adequate method for
     the investigation of the functional organization of the somatosensory cortex in
     upper limb amputees and suggest high stability of cortical reorganization in these
     subjects.

     PMID: 12537305 [PubMed - indexed for MEDLINE]


Conclusion


  Reference

  Ashton H, Golding JF, Marsh VR, Thompson JW. Effects of transcutaneous
  electrical nerve stimulation and aspirin on late somatosensory evoked
  potentials in normal subjects.
  : Pain. 1984 Apr;18(4):377-86.


    1. Relevancy:    Type: Article      Size: 1 KB
       10/10
                                                                                Transcutaneous
                                                                                electrical nerve
                                                                                stimulation
                                                                                (TENS) in
                                                                                neuropathic
                                                                                pain
                                                                                By: B. Disselhoff
                                                                                Found in: Volume
                                                                                12, Issue 2, Jun
                                                                                2000
                                                                                Pages: 145-146
                                                                                From: The Pain
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                     Pages: 149-150
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                     Transcutaneous electrical nerve stimulation (TENS) during
                     epidural steroids injection: a randomized controlled trial
                     By: M. Presser; J. Birkhan; R. Adler; A. Hanani; E. Eisenberg
                     Found in: Volume 12, Issue 2, Jun 2000
                     Pages: 77-80
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                     Esophageal Visceral Pain Sensitivity (Effects of TENS and
                     Correlation with Manometric Findings)
                     By: Mats Borjesson
                     Found in: Volume 43, Issue 8, Aug 1998
                     Pages: 1621-1628
                     From: Digestive Diseases and Sciences
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                     Rehabilitation of patellofemoral pain syndrome: TENS versus
                     diadynamic current therapy for pain relief
                     By: Filiz Can; Reha Tando&gbreve;an; Ilker Yilmaz; Ebru Dolunay; Zafer
                     Erden
                     Found in: Volume 15, Issue 1, Mar 2003
                     Pages: 61-68
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                     Patient reports of the effects and side-effects of TENS for chronic
                     non-malignant pain following a four week trial
                     By: C. D. Richardson; K. Maciver; M. Wright; J. R. Wiles
                     Found in: Volume 13, Issue 3, Sep 2001
                     Pages: 265-276
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                     Rectal Hypersensitivity Reduced by Acupoint TENS in Patients
                     with Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot
                     Study
                     By: Wen-Bin Xiao; Yu-Lan Liu
                     Found in: Volume 49, Issue 2, Feb 2004
                     Pages: 312-319
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     Pubmed

Cortical plasticity and SEPs <9>

1:   Matsunaga K, Nitsche MA, Tsuji S, Rothwell JC.                Related Articles, Links
     Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked
     potentials in humans.
     Clin Neurophysiol. 2004 Feb;115(2):456-60.
     Sobell Department of Motor Neuroscience and Movement Disorders, Institute of
     Neurology, 8-11 Queen Square, London WC1N 3BG, UK.

     OBJECTIVE: To study the after-effect of transcranial direct current stimulation
     (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials
     (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right
     or left median nerve at the wrist before and after anodal or cathodal tDCS in 8
     healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current
     strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal
     components) and P22/N30 (frontal component) following right median nerve
     stimulation were significantly increased for at least 60 min after the end of anodal
     tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal
     component) were unaffected. There was no effect on SEPs evoked by left median
     nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of
     either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce
     a long-lasting increase in the size of ipsilateral cortical components of SEPs.
     SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans
     and might be a useful tool to induce plasticity in cortical sensory processing.
        Rosso T, Aglioti SM, Zanette G, Ischia S, Finco G, Farina S, Fiaschi Related Articles, Links
     2: A, Tinazzi M.
        Functional plasticity in the human primary somatosensory cortex following acute
        lesion of the anterior lateral spinal cord: neurophysiological evidence of short-
        term cross-modal plasticity.
        Pain. 2003 Jan;101(1-2):117-27.
        Dipartimento di Scienze Neurologiche e della Visione, Sezione di Neurologia
        Riabilitativa, Universita di Verona, Policlinico 'G B Rossi', P le A L Scuro, 37134,
        Verona, Italy.

        The primary somatosensory cortex (S1) in adult animals and humans is capable of
        rapid modification after deafferentation. These plastic changes may account for a
        loss of tonic control by nociceptive inputs over inhibitory mechanisms within
        structures of the dorsal column-medial lemniscal system. Most studies, however,
        have been performed under conditions where deafferentation of C and A delta
        fibres coexists with large-diameter fibres deafferentation.In this study the effect of
        the acute lesion of one ascending anterior lateral column on neuronal activity
        within the dorsal column-medial lemniscal system was assessed by recording
        somatosensory evoked potentials (SEPs) in seven patients who underwent
  unilateral percutaneous cervical cordotomy (PCC) as treatment for drug-resistant
  malignant pain.Spinal, brainstem and cortical SEPs were recorded 2h before and
  3h after PCC by stimulating the posterior tibial nerve at both ankles. Amplitudes
  of cortical potentials obtained by stimulation of the leg contralateral to PCC were
  significantly increased after PCC. No significant changes in spinal or brainstem
  potentials were observed. PCC did not affect SEP components obtained by
  stimulation of the leg ipsilateral to PCC.Our results suggest that nociceptive
  deafferentation may induce a rapid modulation of cortical neuronal activity along
  the lemniscal pathway, thus providing the first evidence in humans of short-term
  cortical plasticity across the spinothalamic and lemniscal systems.
                                                                Related Articles, Links
3: Chen AC, Shimojo M, Svensson P, Arendt-Nielsen L.
   Brain dynamics of scalp evoked potentials and current source densities to
   repetitive (5-pulse train) painful stimulation of skin and muscle: central correlate
   of temporal summation.
  Brain Topogr. 2000 Fall;13(1):59-72.
  Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-
  Motor Interaction, Aalborg University, Denmark. ac@smi.auc.dk

  Temporal summation is a potent central somatosensory mechanism and may be a
  major mechanism involved in e.g. neuropathic pain. This study assessed the long-
  latency somatosensory evoked potentials (SEPs) in response to trains of repeated
  painful electrical stimulation of human skin and muscle in order to investigate the
  cerebral representation of temporal summation. Forty series of stimuli were
  delivered at stimulus intensities corresponding to moderate pain levels in 20
  young men. Each series consisted of a five-burst-pulses (1 ms) train delivered at 2
  Hz, known to activate temporal summation, i.e. increased pain intensity during the
  series of stimuli. Grand mean averaged waveforms (31 ch. EEG) were obtained in
  response to the skin and muscle stimulation. In the "train" SEPs, the wave
  morphology was characterized by four peak components after the first stimulus
  (100 to 450 ms) and by three components after the fifth stimulus (2100-2145 ms).
  The latency was significantly prolonged for muscle stimulation only. The 3D
  topographic maps at the peak activation time (100, 140, 250, and 450 ms) showed
  clear reduction in the amplitudes and their spatial extent (P4/P100-Fc2/N100,
  POz/P140-Fc2/N140, Cz/P250, Cz/N460) betweenthe first and the fifth stimulus.
  The current source density (CSD) topology exhibited markedly differential
  patterns changing from the first to the fifth stimulus. For the skin stimulation, the
  fifth stimulus was associated with a distinct emergence of the frontal negativity
  source at Fc2 right frontal cortex. This was consistent across the 100,140, 250, and
  450 peak components but was not even visible in the first stimulus. In the muscle,
  the fifth stimulus was associated with a marked reduction of the frontal positivity
  at contralateral F4 site in the early stages at 100 and 140 ms, and with a total
  disappearance of positive source at Cz. In summary, this study demonstrated a
  clear temporal summation of psychophysical ratings, reduction of the peak
  amplitudes in the last of the first stimuli, dissociation from simple amplitude
  increase of the cerebral responses to pain, and a concurrent transformation of the
   CSD patterns. This change in "rapid cortical dynamics" of short-term plasticity
   could be an important mechanism for wind-up and pain processing in the brain.
   Bernasconi A, Bernasconi N, Lassonde M, Toussaint PJ, Meyer E, Related Articles, Links
4: Reutens DC, Gotman J, Andermann F, Villemure JG.
   Sensorimotor organization in patients who have undergone hemispherectomy: a
   study with (15)O-water PET and somatosensory evoked potentials.
   Neuroreport. 2000 Sep 28;11(14):3085-90.
   Montreal Neurological Hospital and Institute, Department of Neurology and Brain
   Imaging Center, McGill University, Quebec, Canada.

   To identify cortical structures that subserve residual motor and sensory function in
   patients with congenital hemiparesis due to a porencephalic cyst, we examined,
   using [(15)O]H2O, PET and somatosensory evoked potentials (SEPs) in three
   patients with left-sided hemiparesis who had undergone hemispherectomy. Motor
   stimulation of the affected hand produced ipsilateral activation in the premotor
   area in all patients, the SMA in two patients, and SII in two patients. Vibrotactile
   stimulation resulted in activation of the ipsilateral SII in all subjects. Median nerve
   stimulation of the affected hand produced ipsilateral long-latency SEPs in fronto-
   centro-parietal areas, whereas stimulation of the non-affected hand produced
   normal early cortical potentials in the contralateral hemisphere. Our results
   suggest that residual function in the paretic hand is warranted through non-
   primary motor and sensory areas, and higher order associative areas in the intact
   hemisphere.
   Tinazzi M, Fiaschi A, Rosso T, Faccioli F, Grosslercher J, Aglioti Related Articles, Links
5: SM.
   Neuroplastic changes related to pain occur at multiple levels of the human
   somatosensory system: A somatosensory-evoked potentials study in patients with
   cervical radicular pain.
   J Neurosci. 2000 Dec 15;20(24):9277-83.
   Dipartimenti di Scienze Neurologiche e della Visione, Sezione di Neurologia
   Riabilitativa and Sezione di Neurochirurgia, Universita di Verona, 37134 Verona,
   Italy, and Dipartimento di Psicologia, Universita di Roma "La Sapienza," and
   Istitut.

   Studies suggest that pain may play a major role in determining cortical
   rearrangements in the adult human somatosensory system. Most studies, however,
   have been performed under conditions whereby pain coexists with massive
   deafferentation (e.g., amputations). Moreover, no information is available on
   whether spinal and brainstem changes contribute to pain-related reorganizational
   processes in humans. Here we assess the relationships between pain and plasticity
   by recording somatosensory-evoked potentials (SEPs) in patients who complained
   of pain to the right thumb after a right cervical monoradiculopathy caused by
   compression of the sixth cervical root, but did not present with clinical or
   neurophysiological signs of deafferentation. Subcortical and cortical potentials
   evoked by stimulation of digital nerves of the right thumb and middle finger were
   compared with those obtained after stimulation of the left thumb and middle finger
   and with those obtained in a control group tested in comparable conditions.
   Amplitudes of spinal N13, brainstem P14, parietal N20 and P27, and frontal N30
   potentials after stimulation of the painful right thumb were greater than those of
   the nonpainful left thumb and showed a positive correlation with magnitude of
   pain. This right-left asymmetry was absent after stimulation of the patients' middle
   fingers and in control subjects. Results suggest that chronic cervical radicular pain
   is associated with changes in neural activity at multiple levels of the
   somatosensory system. The absence of correlation between the amplitude of
   spinal, brainstem, and cortical components of SEPs suggests that enhancement of
   cortical activity is not a simple amplification of subcortical enhancement.
   Schmitz F, Besselmann M, Bettag M, Neubauer M, Schmitz P, Kiwit Related Articles, Links
6: J, Kunesch E.
   Somatosensory evoked potentials modified by laser-induced lesions of the rat
   cortex.
   Behav Brain Res. 1997 Mar;84(1-2):161-6.
   Department of Neurosurgery, Heinrich-Heine University, Dusseldorf, Germany.

   The effect of focal application of laser energy on the modification of
   somatosensory evoked potentials (SEPs) was studied in sensory cortical fields of
   the rat. This article describes the methodological set-up for recording of SEPs and
   for determining location and size of the laser-induced lesion. The results show that
   both the size of the lesion of the somatosensory cortex, and the suppression and
   time of recovery of cortical SEPs varied depending on the laser energy dose. It
   remains to be analyzed by further experiments if the recovery of SEPs is due to a
   transient dysfunction of the somatosensory cortex or if it reflects cortical
   plasticity.
   Tinazzi M, Zanette G, Polo A, Volpato D, Manganotti P, Bonato C, Related Articles, Links
7: Testoni R, Fiaschi A.
   Transient deafferentation in humans induces rapid modulation of primary sensory
   cortex not associated with subcortical changes: a somatosensory evoked potential
   study.
   Neurosci Lett. 1997 Feb 14;223(1):21-4.
   Dipartimento di Scienze Neurologiche e della Visione, Sez. di Neurologia,
   Verona, Italy.

   Human somatosensory cortex (S1) is capable of rapid modification after
   temporary peripheral deafferentation but it is not known whether subcortical
   changes contribute to this modulation. We recorded spinal, brainstem and cortical
   somatosensory evoked potentials (SEPs) to median nerve stimulation following
   anaesthetic block of the ipsilateral ulnar nerve. Spinal N13 and subcortical P14,
   N18 potentials remained unchanged during the experiment. N20/P20, P27 and
   N30 cortical potentials, which are generated in different subareas of the S1
   (N20/P20, N30 in area 3b; P27 in area 1), showed different increases in amplitude
   during the anaesthesia, which were more marked for N20/P20 and N30 than for
  P27 potentials. These results suggest that changes in S1 neural activity induced by
  transient deafferentation may be primarily intracortical in origin and appear to be
  segregated within the different subareas of the somatosensory cortex. Unmasking
  of pre-existing thalamo-cortical projections from median nerve territories, induced
  by ipsilateral ulnar nerve deafferentation, may be the mechanism underlying
  cortical SEP enhancement.
                                                              Related Articles, Links
8: McLaughlin DF, Kelly EF.
   Evoked potentials as indices of adaptation in the somatosensory system in
   humans: a review and prospectus.
  Brain Res Brain Res Rev. 1993 May-Aug;18(2):151-206. Review.
  University of North Carolina, Chapel Hill 27599.

  Population-level behavior of large neural aggregates can be efficiently monitored
  by corresponding population-level indices such as somatosensory evoked
  potentials (SEPs). The literature reviewed clearly indicates that SEPs undergo
  systematic and often marked changes under conditions of repetitive stimulation.
  Similar results have been reported for several mammalian species and with a
  diversity of stimulation, recording and analysis protocols. The most characteristic
  finding is a loss of SEP component amplitude as a function of decreasing time
  between stimulus presentations. The effects become larger and appear at longer
  ISIs at higher levels of the somatosensory pathway, are more readily evoked by
  stimulus trains than by stimulus pairs and are most pronounced for response
  components generated in the upper cortical layers. These findings are consistent
  with a recently proposed neurophysiological model of short-term plasticity in
  somatosensory cortex, which incorporates detailed and current information on
  cortical microcircuitry, receptor and neurotransmitter characteristics,
  topographical organization and dynamic response to repetitive sensory drive.
  Recommendations are provided for further research, emphasizing the potential of
  frequency-domain analysis methods in conjunction with mechanical vibrotactile
  stimuli as a vehicle for more detailed testing of the proposed neurophysiological
  model and for closer integration with psychophysical studies of vibrotactile
  adaptation.
                                                                 Related Articles, Links
9: Pascual-Leone A, Torres F.
   Plasticity of the sensorimotor cortex representation of the reading finger in Braille
   readers.
  Brain. 1993 Feb;116 ( Pt 1):39-52.
  Human Cortical Physiology Unit, National Institute of Neurological Disorders and
  Stroke, NIH, Bethesda, MD 20892.

  We studied the organization of the somatosensory cortex in proficient Braille
  readers, recording somatosensory evoked potentials (SEPs) in 10 subjects and
  using transcranial magnetic stimulation (TMS) in five subjects, and compared the
  results with those of 15 control subjects. Somatosensory evoked potentials were
  elicited by a focal electrical stimulus to the tip of the index finger and recorded
from a contralateral 4 x 4 grid of scalp electrodes centred around C3' and C4'.
Transcranial magnetic stimulation, with an 8-shaped coil centred over the same
scalp positions, was delivered simultaneously with, and at different intervals after,
the finger stimulus. The results of the right index (reading) finger in Braille
readers were compared with those of their left index (non-reading) finger and of
the right and left index fingers of the control subjects. The scalp areas from which
we recorded N20 and P22 components of the SEP with an amplitude of at least
70% of the maximal amplitude recorded in each trial were significantly larger in
SEPs evoked from the reading fingers. Detection of the stimulus applied to the
reading finger was blocked by TMS delivered over a larger contralateral scalp area
and during a longer time window after the stimulus. These experiments suggest
that reading Braille is associated with expansion of the sensorimotor cortical
representation of the reading finger.
TENs and SEP <8>

1:   Everaert K, De Muynck M, Rimbaut S, Weyers S.                 Related Articles, Links
     Urinary retention after hysterectomy for benign disease: extended diagnostic
     evaluation and treatment with sacral nerve stimulation.
     BJU Int. 2003 Apr;91(6):497-501.
     Department of Urology, Ghent University Hospital, Ghent, Belgium.
     karel.everaert@rug.ac.be

     OBJECTIVE: To detect prospectively neurogenic damage in patients with urinary
     retention responding to sacral nerve stimulation (SNS) after hysterectomy for benign
     disease. PATIENTS AND METHODS: From August 1995 to February 2002, 13 of
     15 patients (mean age 43 years, sd 7) with urine retention for a mean (sd, range) of
     25 (22, 6-240) months after hysterectomy for benign disease, were prospectively
     evaluated and treated with SNS. They were assessed using urodynamics at baseline
     and during the test stimulation. Sensory evoked potentials (SEPs), electrical sensory
     threshold (EST) measurements of the pudendal nerve, bladder neck and the bladder
     (2 Hz, 0-300 V), and needle electromyography of the external urethral sphincter
     (EUS) were undertaken in all patients. RESULTS: De-afferentiation (EST >/= 200
     V) was limited to the bladder in four of the 13 patients and extended to the bladder
     neck in one other, and was matched by no response at the SEP. Relative ESTs of the
     bladder neck correlated inversely with residual urine (r = - 0.76, P = 0.01, x = 546, fx
     = 1.22) and bladder capacity (r = - 0.77, P = 0.01, x = 611, fx = 1.26) at diagnosis.
     Complex repetitive discharges and decelerating bursts of the EUS were seen in these
     five patients. Unilateral SNS was applied in 10 patients (bilateral in three). A
     revision was needed in six patients. Uroflowmetry at the last follow-up showed a
     mean (sd) maximum urinary flow rate of 22 (18) mL/s (not significantly different
     from during trial stimulation) with residual urine of 50-100 mL in two and 200-400
     mL in three patients. Intermittent catheterization was needed in four patients.
     CONCLUSION: Urinary retention after hysterectomy for benign disease is
     associated with de-afferentiation of the bladder wall in some patients and is
     correlated inversely with the relative EST of the bladder neck. A Fowler syndrome
     was detected in five patients. For residual urine, about half the patients have a good
     and a third a partial long-term effect; we now offer SNS as a further treatment
     option.
                                                                     Related Articles, Links
     2: Hu Y, Yu J.
        [A study on distribution modeling of the electrical stimulation under surface nerve
        stimulation electrodes for somatosensory evoked potential]
       Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 1999 Dec;16(4):462-6. Chinese.
       College of Precision Instrument and Optical Electronic Engineering, Tianjing
       University, Tianjing 300072.

       The detection of somatosensory evoked potential (SEP) has been an important
       approach to determining the function of spinal cord and peripheral nerve.
   Transepidermal Electrical Neuromuscular Stimulation (TENS) on the posterior
   tibial nerve for SEP is one of the applications and can improve the effectiveness.
   This paper theoretically studies the distribution of potential field and current
   density field for human tissue under TENS. A mirror method is used and the
   analytical solution of the potential distribution is obtained.
   Rossi S, Tecchio F, Pasqualetti P, Ulivelli M, Pizzella V, Romani GL, Related Articles, Links
3: Passero S, Battistini N, Rossini PM.
   Somatosensory processing during movement observation in humans.
   Clin Neurophysiol. 2002 Jan;113(1):16-24.
   Dipartimento di Neuroscienze, Sezione Neurologia, UO Neurofisiopatologia,
   Universita di Siena, Policlinico Le Scotte, Viale Bracci, 53100 Siena, Italy.
   rossisimo@unisi.it

   OBJECTIVES: A neural system matching action observation and execution seems
   to operate in the human brain, but its possible role in processing sensory inputs
   reaching the cortex during movement observation is unknown. METHODS: We
   investigated somatosensory evoked potentials (SEPs), somatosensory evoked
   fields (SEFs) and the temporal spectral evolution of the brain rhythms
   (approximately 10 and approximately 20 Hz) following electrical stimulation of
   the right median nerve in 15 healthy subjects, during the following randomly
   intermingled conditions: a pure cognitive/attentive task (mental calculation); the
   observation of a motoric act (repetitive grasping) with low cognitive content
   ('Obs-grasp'); and the observation of a complex motoric act (finger movement
   sequence), that the subject had to recognize later on, therefore reflecting an
   adjunctive cognitive task ('Obs-seq'). These conditions were compared with an
   absence of tasks ('Relax') and actual motor performance. RESULTS: The post-
   stimulus rebound of the approximately 20 Hz beta magnetoencephalographic
   rhythm was reduced during movement observation, in spite of little changes in the
   approximately 10 Hz rhythm. Novel findings were: selective amplitude increase of
   the pre-central N(30) SEP component during both 'Obs-grasp' and 'Obs-seq', as
   opposed to the 'gating effect' (i.e. amplitude decrease of the N(30)) occurring
   during movement execution. The strength increase of the 30 ms SEF cortical
   source significantly correlated with the decrease of the approximately 20 Hz post-
   stimulus rebound, suggesting a similar pre-central origin. CONCLUSIONS:
   Changes took place regardless of either the complexity or the cognitive content of
   the observed movement, being related exclusively with the motoric content of the
   action. It is hypothesized that the frontal 'mirror neurons' system, known to
   directly facilitate motor output during observation of actions, may also modulate
   those somatosensory inputs which are directed to pre-central areas. These changes
   are evident even in the very first phases (i.e. few tens of milliseconds) of the
   sensory processing.
                                                            Related Articles, Links
4: Umino M, Ohwatari T, Nagao M.
   A new method of recording somatosensory evoked potentials by randomized
   electrical tooth stimulation with 6 levels of intensity.
   Pain. 1996 Feb;64(2):269-76.
  Department of Geriatric Dentistry, Faculty of Dentistry, Tokyo Medical and
  Dental University, Japan.

  Dental somatosensory evoked potentials (SEPs) corresponding to the stimulus
  intensity levels were recorded at 6 different levels of intensity presented in a
  randomized order. The relationships between the amplitude of the late SEP
  component with latency between 150 and 300 msec and each stimulus intensity
  level were also compared in conditions of randomized intensity and constant
  intensity. The amplitude of the late component increased significantly with the
  increased stimulus intensity both in the randomized and constant intensity
  stimulation. The amplitude of the late component in the randomized stimulation
  with a 1-sec interstimulus interval (ISI) increased in the same manner as that in the
  constant intensity condition with a 1-sec ISI. The randomized stimulation with the
  prolonged ISI increased the amplitude of the late component. The latency of the
  late positive component significantly increased with the randomized stimulation
  with a 3-sec ISI. This phenomenon might be attributable to the psychological
  contamination. SEP recording in the randomized dental stimulation with a 1-sec
  ISI may have applications in neuropharmacological research or physiological
  research on pain and evaluation of the effects of analgesics, anesthetics,
  acupuncture and transcutaneous electrical nerve stimulation (TENS).
                                                                Related Articles, Links
5: Akyuz G, Guven Z, Ozaras N, Kayhan O.
   The effect of conventional transcutaneous electrical nerve stimulation on
   somatosensory evoked potentials.
  Electromyogr Clin Neurophysiol. 1995 Oct;35(6):371-6.
  Marmara University Medical Faculty, Department of Physical Medicine and
  Rehabilitation, Istanbul, Turkey.

  Transcutaneous electrical nerve stimulation (TENS) is an electrotherapeutic
  modality used for analgesia. We planned to demonstrate selective stimulation of
  large diameter fibers with conventional type TENS by way of somatosensory
  evoked potentials (SEP). We have analyzed index finger-wrist segment median
  nerve sensory potential and SEP recordings obtained from C2 and Cc before
  TENS and at 5, 10 and 15 minutes of TENS application of 14 adult healthy
  volunteers. SEP and finger-wrist segment sensory nerve conduction amplitudes
  were significantly decreased compared to pre-TENS values during 5, 10, and 15
  minutes of TENS application (p < 0.05). These results reflect the selective
  stimulation of large diameter afferent fibers of conventional type TENS.
                                                                 Related Articles, Links
6: Yamashiro H, Hara K, Gotoh Y.
   [Relief of intractable post-herpetic neuralgia with gasserian ganglion block using
   methyl prednisolone acetate and with TENS]
  Masui. 1990 Sep;39(9):1239-44. Japanese.
  Department of Anesthesia, Hamamatsu Medical Center.

  A 58 year old man had been suffering from intractable left ophthalmic post
  herpetic neuralgia (PHN) for 7 years. He has also been treated for polyarteritis
  nodosa for 10 years. For pain relief, he was treated initially with frequent (4 times
  a day) stellate ganglion block (SGB) and peripheral ophthalmic nerve block for a
  month without relief. Then supraorbital nerve block with neurolytics, TENS and
  acupuncture were done with a slight relief of his pain. Recently his pain became
  worse even with imipramine 75 mg and carbamazepine 100 mg a day which
  relieved effectively the patient from the pain for the last 3 years. The pain was so
  severe to disturb his usual daily activity. Gasserian ganglion block with methyl
  prednisolone acetate 10 mg was done. After the block, his ADL improved
  markedly. Three months after the block, he had no spontaneous pain and slight
  pain with light touch on the injured skin did not annoy him. Several days before
  the block, electric stimulation to control his pain was tested. Stimulation with the
  electricity (4.5 mA, 10 cycle and 400 microseconds) brought him complete relief
  from the pain during the stimulation. Trigeminal SEP showed no response to the
  stimulation of injured skin.
                                                                Related Articles, Links
7: Briand A, Duparc VF, Pottier M.
   [Changes in cortical evoked potentials in relation to cutaneous sensory thresholds.
   Application to a study of analgesic electrostimulation]
  Rev Electroencephalogr Neurophysiol Clin. 1985 Jul;15(1):65-76. French.
  The potentials (EPs) evoked by cutaneous electric shock of increasing intensity
  and the corresponding sensitivity thresholds were studied in 25 healthy volunteers:
  analgesic electrical stimulation (AES) was performed on only 10 of these. The
  stimuli (0.5 msec; 0-140 V) applied in a random way with a needle electrode
  implanted in the horny layer of the tip of the middle finger can produce 4
  sensations: initial awareness, pressure sensation, diffusion and pain. The EP
  recorded on the somatosensory areas had the typical somatosensory (SEP)
  morphology only at the pressure stage. At the pain thresholds, the response was a
  well-demarcated 'nociceptive' EP (NEP), with main components at P100, N140,
  P240. After 45 min of AES, the increase of the sensitivity thresholds was
  peculiarly pronounced for that of pain, homolaterally (80%) and contralaterally
  (45%) to the AES. With respect to the EPs, the NEP and especially its late waves
  showed a noteworthy reduction in amplitude, more significant on the homolateral
  side (66%) than on the contralateral one (50%), whilst the SEP was only slight
  modified. The evolution of the thresholds and of the EPs was followed for 45 min
  after cessation of AES and revealed a significant residual effect of comparable
  values for the two parameters.
                                                                Related Articles, Links
8: Ashton H, Golding JF, Marsh VR, Thompson JW.
   Effects of transcutaneous electrical nerve stimulation and aspirin on late
   somatosensory evoked potentials in normal subjects.
  Pain. 1984 Apr;18(4):377-86.
  The effects on late somatosensory evoked potentials (SEPs) of transcutaneous
  nerve stimulation (TENS) and aspirin (600 mg), compared with placebo, were
  studied in 32 young, healthy male and female volunteers. SEPs were produced by
  electrical stimulation of the median nerve at moderate, non-painful, intensities.
There was a reduction in the peak-to-peak amplitude of the late components N1P2
(N1 latency: 100-160 msec; P2 latency: 160-260 msec) of the SEP in all groups
over time. TENS but not aspirin produced further significant changes compared
with placebo, including a fall in N1P2 amplitude, an increase in N1 latency, and a
decrease in the total excursion of the SEP between 25 and 450 msec after stimulus
onset.
acupuncture and SEP <9>

1:                                                             Related Articles, Links
     Meissner W, Weiss T, Trippe RH, Hecht H, Krapp C, Miltner WH.
     Acupuncture decreases somatosensory evoked potential amplitudes to noxious
     stimuli in anesthetized volunteers.
     Anesth Analg. 2004 Jan;98(1):141-7, table of contents.
     Department of Anesthesiology and Intensive Care, Friedrich-Schiller-University
     Jena, 07740 Jena, Germany. meissner@med.uni-jena.de

     The effect of acupuncture on pain perception is controversial. Because late
     amplitudes of somatosensory evoked potentials (SEPs) to noxious stimuli are
     thought to correlate with the subjective experience of pain intensity, we designed this
     study to detect changes of these SEPs before and after acupuncture in a double-
     blinded fashion. Sixteen volunteers were anesthetized by propofol and exposed to
     painful electric stimuli to the right forefinger. Then, blinded to the research team, the
     acupuncture group (n = 8) was treated with electric needle acupuncture over 15 min
     at analgesic points of the leg, whereas the sham group (n = 8) received no treatment.
     Thereafter, nociceptive stimulation was repeated. SEPs were recorded during each
     noxious stimulation from the vertex Cz, and latencies and amplitudes of the N150
     and P260 components were analyzed by analysis of variance. P260 amplitudes
     decreased from 4.40 +/- 2.76 microV (mean +/- SD) before treatment to 1.67 +/-
     1.21 microV after treatment (P < 0.05), whereas amplitudes of the sham group
     remained unchanged (2.64 +/- 0.94 microV before versus 2.54 +/- 1.54 microV after
     treatment). In conclusion, this double-blinded study demonstrated that electric needle
     acupuncture, as compared with sham treatment, significantly decreased the
     magnitudes of late SEP amplitudes with electrical noxious stimulation in
     anesthetized subjects, suggesting a specific analgesic effect of acupuncture.
     IMPLICATIONS: This double-blinded study demonstrates that electric needle
     acupuncture, as compared with sham treatment, significantly decreases the
     magnitudes of late somatosensory evoked potential amplitudes with electrical
     noxious stimulation in anesthetized subjects, suggesting a specific analgesic effect of
     acupuncture.
                                                                   Related Articles, Links
     2: Wei H, Kong J, Zhuang D, Shang H, Yang X.
        Early-latency somatosensory evoked potentials elicited by electrical acupuncture
        after needling acupoint LI-4.
       Clin Electroencephalogr. 2000 Jul;31(3):160-4.
       Second Department of Internal Medicine, Guang An Men Hospital, China
       Academy of Traditional Chinese Medicine, Beijing, P. R. China.

       The stimulating methods of prior studies on somatosensory evoked potentials
       (SEPs) elicited by acupoint stimulus had involved surface electrodes, while the
       clinical practice of acupuncture is mostly performed by inserting the acupuncture
       needle inside the body. Clinical observations show that there are often some
       special sensations when LI-4 is needled. To observe if the SEPs produced by
  acupoint acupuncture had a distinguishing property, we studied the SEPs elicited
  by electrical acupuncture after the acupuncture needle was inserted into LI-4 and
  its control point, and then mapped them with the 128-channel Electric Brain
  Signal Image system. We also compared this to SEPs by median nerve stimuli.
  Results showed that the most interesting finding was the marked differences of
  N1-P1 and N2-P2 amplitude between SEPs at LI-4 (SEP-LI) and its control point
  (SEP-CP), which were in the opposite direction. Marked differences were also
  found between latencies and amplitudes of the SEPs elicited by acupuncture and
  by median nerve stimulus (SEP-M). The differences between SEP-LI and SEP-CP
  might be due to the additional effects of the activation of nerve endings and
  muscle spindles in LI-4 to the SEPs formed by the activation of superficial and
  deep radial nerves during electrical acupuncture. The differences between SEPs to
  acupoint and median nerve stimuli might be mainly due to the different distances
  from the stimulated regions to the cerebral cortex, the diversity and the number of
  activated fibers.
                                                                Related Articles, Links
3: Chen Z, Geng Z, Zhang J, Zhao Y, Gao Y, Zhang X.
   [The effect of electric acupuncture on SEP of local cerebral ischemic-reperfusion
   rats]
  Zhen Ci Yan Jiu. 1996;21(4):34-40. Chinese.
  Beijing College of Acupuncture and Orthopedics.

  The results suggest that 3 hours after cerebral ischemia, the P1-N1 amplitudes of
  the somatosensory evoked potential (SEP) of the cerebral cortex decrease
  significantly by the stimulation of cerebrum, while the latency period of both
  wave P1 and P2 prolonged; 2 hours later, the abnormal data of SEP have not any
  improvement. These suggest that the post-ischemic cortex and subcortical neurons
  were injured permanently by a substantial lesions from reperfusional injuries.
  Cerebral tissue histologic studies show that the infarcted focus locates in caudate
  nucleus and lateral cortex of cerebral hemisphere. But after electric acupuncture at
  Huantiao at the late stage of cerebral ischemia of rats, the abnormal data of SEP
  show better recoveries and manintains till 2 hours after reperfusion, and even near
  to that of the normal rat. All of them suggest acupuncture is effective obviously
  for ischemic injury of cerebral tissue, and possesses a presetting protection for
  reperfusional injury of cerebral tissue. So it is concluded that the efficacy of
  acupuncture results from its comprehensive and optimal regulation function to
  multisystem of the whole body.
                                                              Related Articles, Links
4: Sing T, Yang MM.
   Electroacupuncture and laser stimulation treatment: evaluated by somatosensory
   evoked potential in conscious rabbits.
  Am J Chin Med. 1997;25(3-4):263-71.
  Department of Physiology, Faculty of Medicine, University of Hong Kong,
  Pokfulam, Hong Kong.

  Tooth pulp generated somatosensory evoked potential (TPSEP) recordings were
  used to evaluate analgesic responses to Electroacupuncture (EA) and laser
  stimulation (Ls) treatments in Dutch-hybrid male rabbits. TPSEP recorded 100
  trials at 30 minute intervals for 120 minutes. Three groups, EA, Ls and control
  were analyzed. The EA group received intermittent 4 Hz, intensity 2-10 volts
  electro-stimulation for twenty minutes. In the Ls group, a gallium aluminium
  arsenide (GaAlAs) laser diode with wavelength 780 nm, switched pulse frequency
  9720 Hz, energy density 0.6 J/point was employed. Both EA and Ls groups
  received stimulation of the points Ho-ku (LI-4) and Tzu-San-Li (ST-36). Results
  showed tooth pulp generated noxious stimulation produced a consistent late near-
  field SEP waveform, which is similar to those recorded in humans and correlated
  to the sensation of pains, thus confirming that tooth pulp stimulation is a reliable
  dolormetric index. EA and Ls TPSEP recordings showed decreased peak-wave
  amplitude in late near-field components. These decreases correlate to analgesia.
  This technique provides an objective and reliable dolormetric index.
                                                            Related Articles, Links
5: Umino M, Ohwatari T, Nagao M.
   A new method of recording somatosensory evoked potentials by randomized
   electrical tooth stimulation with 6 levels of intensity.
  Pain. 1996 Feb;64(2):269-76.
  Department of Geriatric Dentistry, Faculty of Dentistry, Tokyo Medical and
  Dental University, Japan.

  Dental somatosensory evoked potentials (SEPs) corresponding to the stimulus
  intensity levels were recorded at 6 different levels of intensity presented in a
  randomized order. The relationships between the amplitude of the late SEP
  component with latency between 150 and 300 msec and each stimulus intensity
  level were also compared in conditions of randomized intensity and constant
  intensity. The amplitude of the late component increased significantly with the
  increased stimulus intensity both in the randomized and constant intensity
  stimulation. The amplitude of the late component in the randomized stimulation
  with a 1-sec interstimulus interval (ISI) increased in the same manner as that in the
  constant intensity condition with a 1-sec ISI. The randomized stimulation with the
  prolonged ISI increased the amplitude of the late component. The latency of the
  late positive component significantly increased with the randomized stimulation
  with a 3-sec ISI. This phenomenon might be attributable to the psychological
  contamination. SEP recording in the randomized dental stimulation with a 1-sec
  ISI may have applications in neuropharmacological research or physiological
  research on pain and evaluation of the effects of analgesics, anesthetics,
  acupuncture and transcutaneous electrical nerve stimulation (TENS).
                                                             Related Articles, Links
6: Xu X, Shibasaki H, Shindo K.
   Effects of acupuncture on somatosensory evoked potentials: a review.
  J Clin Neurophysiol. 1993 Jul;10(3):370-7. Review.
  Department of Brain Pathophysiology, Kyoto University Faculty of Medicine,
  Japan.
  Although acupuncture has a long history of analgesic effects, the mechanisms
  underlying its effects are still unclear. Somatosensory evoked potential (SEP)
  methodology has been adopted in the research of acupuncture since the 1970s. In
  research on the effects of acupuncture on the conventional SEP, variable results
  have been observed, and two different opinions concerning the presence or
  absence of acupuncture effects on the conventional SEP are discussed. Since the
  conventional SEP is mediated mainly by fast conducting sensory nerve fibers, the
  conventional SEP methodology, especially that for recording short-latency SEP,
  may be inadequate for studying acupuncture mechanisms. In the case of the long-
  latency cortical SEP, there are too few data available to judge the effects of
  acupuncture analgesia (AA). Studies on the effects of AA on pain SEPs
  demonstrated that AA has a suppressive effect on amplitude of the pain SEP (and
  affecting the latency as well in some experiments) in both animals and humans,
  being accompanied by increased pain threshold. Thus, acupuncture seems to have
  analgesic effects that are probably related to activation of the antinociceptive
  system, and application of the pain SEP methodology to the study of mechanisms
  of AA may be promising.
                                                                 Related Articles, Links
7: Yamashiro H, Hara K, Gotoh Y.
   [Relief of intractable post-herpetic neuralgia with gasserian ganglion block using
   methyl prednisolone acetate and with TENS]
  Masui. 1990 Sep;39(9):1239-44. Japanese.
  Department of Anesthesia, Hamamatsu Medical Center.

  A 58 year old man had been suffering from intractable left ophthalmic post
  herpetic neuralgia (PHN) for 7 years. He has also been treated for polyarteritis
  nodosa for 10 years. For pain relief, he was treated initially with frequent (4 times
  a day) stellate ganglion block (SGB) and peripheral ophthalmic nerve block for a
  month without relief. Then supraorbital nerve block with neurolytics, TENS and
  acupuncture were done with a slight relief of his pain. Recently his pain became
  worse even with imipramine 75 mg and carbamazepine 100 mg a day which
  relieved effectively the patient from the pain for the last 3 years. The pain was so
  severe to disturb his usual daily activity. Gasserian ganglion block with methyl
  prednisolone acetate 10 mg was done. After the block, his ADL improved
  markedly. Three months after the block, he had no spontaneous pain and slight
  pain with light touch on the injured skin did not annoy him. Several days before
  the block, electric stimulation to control his pain was tested. Stimulation with the
  electricity (4.5 mA, 10 cycle and 400 microseconds) brought him complete relief
  from the pain during the stimulation. Trigeminal SEP showed no response to the
  stimulation of injured skin.
                                                            Related Articles, Links
8: Kang DX, Ma BR, Lundervold A.
   The effect of acupuncture on somatosensory evoked potentials.
  Clin Electroencephalogr. 1983 Jan;14(1):53-6.
  After manual acupuncture in the Neiguan point no significant difference was
  detected on early component N9, N13, N20, as well as, the negative potential after
  N20 from 22 subjects with normal SEP. However in one patient with abnormal
  SEP the latencies were sometimes improved after acupuncture when the
  acupuncture simultaneously decreased the pain.
                                                             Related Articles, Links
9: Saletu B, Saletu M, Brown M, Stern J, Sletten I, Ulett G.
   Hypno-analgesia and acupuncture analgesia: a neurophysiological reality?
  Neuropsychobiology. 1975;1(4):218-42.
  The effects of hypnosis, acupuncture and analgesic drugs on the subjective
  experience of pain and on objective neurophysiological parameters were
  investigated. Pain was produced by brief electric stimuli on the wrist. Pain
  challengers were: hypnosis (induced by two different video tapes), acupuncture (at
  specific and unspecific loci, with and without electrical stimulation of the
  needles), morphine and ketamine. Evaluation of clinical parameters included the
  subjective experience of pain intensity, blood pressure, puls, temperature,
  psychosomatic symptoms and side effects. Neurophysiological parameters
  consisted of the quantitatively analyzed EEG and somatosensory evlked potential
  (SEP). Pain was significantly reduced by hypnosis, morphine and ketamine, but
  not during the control seesion. Of the four acupuncture techniques, only electro-
  acupuncture at specific loci significantly decreased pain. The EEG changes during
  hypnosis were dependent on the wording of the suggestion and were characterized
  by an increase of slow and a decrease of fast waves. Acupuncture induced just the
  opposite changes, which were most significant when needles were inserted at
  traditional specific sites and stimulated electrically. The evoked potential findings
  suggested that ketamine attenuates pain in the thalamo-cortical pathways, while
  hypnosis, acupuncture and morphine induce analgesia at the later CNS stage of
  stimulus processing. Finally some clinical-neurophysiological correlations were
  explored.
Dear Joyce:

Wangli and I have discussed the state of data and the complications associated with them.

Since you have finished medical school and have time to "think", it is better that you take up the original
agreement that you shall be the first author if you contribute effectively on the paper.

Here is what we need to do:
A. You may read the poster we made for the HBM-2004 (attached).
B. Expand it into a short paper for Neuroscience Letters (NSL, 5 printed page, a sample is attached for
you).
C. You need to survey the literature on EEG and somatosentory stimulation, i.e. acupuncture and
transcuataneous electrical stimulation; then summarize them on the Introduction section.
D. Stress the lack of temporal-spatial dynamic in EEG, which may reveal the effective changes in human
brain. We have a control (low intensity stimulation) vs. treatment (high intensity stimulation).
E. We focus the these two conditions and make a statement on "when" and "where" the true acupuncture
exerts the EEG power mapping changes.

We shall, in the future, followed up with the main-effect from this NSL paper to compare the Pre and Post
stages of EEG for our next paper. If we do it now, it will be too complicated (needs a huge effort of time to
sort out of group data) to dimish our original intend on this study.

So, if you can agree to do the above you shall be kept as the first author.

Please just read the enclosed literatures (you just touch the authors to get the internet connection, then find
the original articles on-line).

We like to finish the m.s. by the end of August, 2004.

Please reply,
Andrew
Enclosures (3)
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