sensory stimulation (tens): effects of parameter...

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Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects Linda S. Chesterton a , Panos Barlas a, * , Nadine E. Foster a , Thomas Lundeberg b , Christine C. Wright c , G. David Baxter d a Department of Physiotherapy Studies, Keele University, Staffordshire ST5 5BG, UK b Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden c School of Health and Social Sciences, Coventry University, Coventry, UK d School of Rehabilitation Sciences, University of Ulster, Jordanstown, Northern Ireland, UK Received 24 September 2001; received in revised form 27 February 2002; accepted 10 April 2002 Abstract Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham- controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at a ¼ 0:05. Subjects were randomised to one of the six TENS groups, a control, and a sham TENS group (n ¼ 30, 15 males, 15 females, per group). TENS groups differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity (‘to tolerance’ or ‘strong but comfortable’) and stimulation site (segmental – over the distribution of the radial nerve or, extrasegmental – over acupuncture point ‘gall bladder 34’, or a combination of both segmental and extrasegmental). Pulse duration was fixed at 200 ms. Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min. Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10-min intervals for 60 min. Difference scores were analysed using repeated measures and one-way ANOVA and relevant post hoc tests. Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimula- tion period (P , 0:0005 control and sham) and was sustained for 30 min post-stimulation (P , 0:0005 control , P ¼ 0:024 sham ). Whilst high frequency, ‘strong but comfortable’ intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post-stimulation. Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects. These results may have implications for the clinical use of sensory stimulation. q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. Keywords: Transcutaneous electrical nerve stimulation; Electrostimulation; Parameters; Mechanical pain; Humans 1. Introduction Transcutaneous electrical nerve stimulation (TENS) is an established form of electrostimulation, which has been used clinically for the treatment of pain for more than 30 years (Ellis, 1998). Despite this clinical popularity and an exten- sive research base, there is little consensus regarding the optimal stimulation parameters required to induce maximal hypoalgesic effects (Walsh and Baxter, 1996). This lack of consensus is partly due to the diverse nature of the pathol- ogies for which TENS is prescribed, and also to the wide range of stimulation variables which must be considered within the prescription (e.g. stimulation site, electrode size, pulse pattern, patient preference, etc). Rigorous systematic reviews of the available literature suggest that few of the published reports regarding TENS therapy meet acceptable methodological standards to underpin recom- mendations for clinical practice (Milne et al., 2001; McQuay and Moore 1998; Carroll et al., 1996, 1997a,b; Flowerdew and Gadsby 1997; Reeve et al., 1996). Specific criticisms include: small sample sizes which lead to low statistical power, a lack of adequate blinding, no control Pain 99 (2002) 253–262 0304-3959/02/$20.00 q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. PII: S0304-3959(02)00118-5 www.elsevier.com/locate/pain * Corresponding author. Tel.: 144-1782-584251; fax: 144-1782- 584255. E-mail address: [email protected] (P. Barlas).

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Page 1: Sensory stimulation (TENS): effects of parameter ...thomaslundeberg.se/uploaded/dokument/publicerade_dokument... · Transcutaneous electrical nerve stimulation ... Transcutaneous

Sensory stimulation (TENS): effects of parameter manipulation onmechanical pain thresholds in healthy human subjects

Linda S. Chestertona, Panos Barlasa,*, Nadine E. Fostera, Thomas Lundebergb,Christine C. Wrightc, G. David Baxterd

aDepartment of Physiotherapy Studies, Keele University, Staffordshire ST5 5BG, UKbDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

cSchool of Health and Social Sciences, Coventry University, Coventry, UKdSchool of Rehabilitation Sciences, University of Ulster, Jordanstown, Northern Ireland, UK

Received 24 September 2001; received in revised form 27 February 2002; accepted 10 April 2002

Abstract

Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there

remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham-

controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site)

upon experimentally induced mechanical pain.

Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at a ¼ 0:05. Subjects were

randomised to one of the six TENS groups, a control, and a sham TENS group (n ¼ 30, 15 males, 15 females, per group). TENS groups

differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity (‘to tolerance’ or ‘strong but comfortable’) and stimulation

site (segmental – over the distribution of the radial nerve or, extrasegmental – over acupuncture point ‘gall bladder 34’, or a combination of

both segmental and extrasegmental). Pulse duration was fixed at 200 ms. Stimulation was delivered for 30 min and subjects were then

monitored for a further 30 min.

Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the

dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10-min intervals for 60 min. Difference

scores were analysed using repeated measures and one-way ANOVA and relevant post hoc tests.

Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimula-

tion period (P , 0:0005 control and sham) and was sustained for 30 min post-stimulation (P , 0:0005control, P ¼ 0:024sham). Whilst high

frequency, ‘strong but comfortable’ intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect

was not sustained post-stimulation. Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects. These

results may have implications for the clinical use of sensory stimulation. q 2002 International Association for the Study of Pain. Published

by Elsevier Science B.V. All rights reserved.

Keywords: Transcutaneous electrical nerve stimulation; Electrostimulation; Parameters; Mechanical pain; Humans

1. Introduction

Transcutaneous electrical nerve stimulation (TENS) is an

established form of electrostimulation, which has been used

clinically for the treatment of pain for more than 30 years

(Ellis, 1998). Despite this clinical popularity and an exten-

sive research base, there is little consensus regarding the

optimal stimulation parameters required to induce maximal

hypoalgesic effects (Walsh and Baxter, 1996). This lack of

consensus is partly due to the diverse nature of the pathol-

ogies for which TENS is prescribed, and also to the wide

range of stimulation variables which must be considered

within the prescription (e.g. stimulation site, electrode

size, pulse pattern, patient preference, etc). Rigorous

systematic reviews of the available literature suggest that

few of the published reports regarding TENS therapy meet

acceptable methodological standards to underpin recom-

mendations for clinical practice (Milne et al., 2001;

McQuay and Moore 1998; Carroll et al., 1996, 1997a,b;

Flowerdew and Gadsby 1997; Reeve et al., 1996). Specific

criticisms include: small sample sizes which lead to low

statistical power, a lack of adequate blinding, no control

Pain 99 (2002) 253–262

0304-3959/02/$20.00 q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

PII: S0304-3959(02)00118-5

www.elsevier.com/locate/pain

* Corresponding author. Tel.: 144-1782-584251; fax: 144-1782-

584255.

E-mail address: [email protected] (P. Barlas).

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group and incompatible methodologies, which prevent

satisfactory aggregation and replication of results. Milne

et al. (2001) specifically identified the lack of experimental

data regarding the hypoalgesic effect of manipulating the

application site and treatment duration, alongside the selec-

tion of optimal frequencies and intensities.

The lack of agreement within the literature regarding the

selection of TENS parameters for therapeutic applications,

has resulted in the development of standard parameter

combinations for clinical use which are referred to as

‘TENS modes’ (Walsh and Baxter, 1996; Walsh, 1997).

These modes include ‘conventional TENS’ (high frequency,

low intensity), and ‘Acupuncture-like TENS’ (low

frequency, high intensity), often called AL-TENS (Johnson,

1998; Walsh, 1997). The pain modulating effect of conven-

tional TENS is traditionally associated with blocked noci-

ceptive transmission in the spinal cord (Garrison and

Foreman, 1996; Melzack and Wall, 1965), and the stimula-

tion site for this mode is therefore around the area of pain or

within the same dermatomal segment. This generates large

diameter afferent barrage to the central nervous system

(CNS) via the spinal cord segment associated with the

reported pain (Johnson, 1998). AL-TENS pain modulation

is associated with endogenous opiates, released via the

descending inhibitory pathways in response to afferent

activity in the A delta fibres (Chen et al., 1998; Sjolund

and Eriksson, 1976). AL-TENS has also been associated

with a counter irritation effect proposed by Le Bars et al.

(1979a) with inhibition of neural pathways in the dorsal

horn being mediated by the rostral ventral medulla

(Basbaum and Fields, 1978). To activate this response,

stimulation must be at intensities capable of inducing force-

ful phasic muscle contractions, usually as high as the patient

can tolerate (Bushnell et al., 1991). Johnson (1998)

proposed that such contractions can be easily achieved by

stimulating motor points or the muscle belly, although trig-

ger points, acupuncture points, distant and contralateral

areas are also promoted as effective stimulation points

(Johnson, 1998; Walsh, 1997). Whilst the evidence to

support the hypoalgesic efficacy of each mode is contradic-

tory, studies of long term TENS users have suggested that

satisfactory hypoalgesic effects are more likely to be

obtained where patients try out different stimulation char-

acteristics and electrode placements (Johnson et al., 1991a;

Eriksson et al., 1979). Indeed, Walsh and Baxter (1996)

cited ineffective electrode placement as one of the primary

factors for poor patient response, and many authors concede

that location of stimulation site is the least investigated

parameter of TENS (Chen et al., 1998; Danziger et al.,

1998; Walsh, 1996, 1997; Johnson et al., 1991b, 1992;

Mannheimer, 1978).

With these concerns in mind, the aim of the current study

was to investigate the comparative hypoalgesic effects of

common clinical TENS modes, using different frequency

and intensity settings, applied at different stimulation

sites. Acupuncture points were explicitly selected for elec-

trode placement as this represents common clinical practice

(the popularity of which may stem from promotional mate-

rial distributed by manufacturers with TENS equipment)

and there is tentative evidence to suggest that stimulation

over such points is more effective than just dermatomal/

segmental stimulation (Chen et al., 1998; Takeshige et al.,

1992a,b).

2. Method

Ethical approval was obtained from the University’s ethi-

cal committee, and a randomised, double blind, controlled

experiment, with repeated measures was used. The experi-

mental groups included six active TENS groups, a control

and a sham TENS group. The stimulation period lasted

30 min, followed by a monitoring period of 30 min. The

outcome variable was the mechanical pain threshold

(MPT) measured before stimulation and at six further 10-

min intervals.

2.1. Subjects

Two hundred and forty volunteers, TENS-naive subjects

(120 females, 120 males) were recruited from the University

student and staff population. The sample size was calculated

according to Cohen (1992), in order to detect an effect size

of $0.5 for pairwise mean comparisons between active

groups and the control, and so that statistical analysis

would be supported by 80% power at a ¼ 0:05 (Cohen,

1992). The mean age of the sample was 30 years

(SD ¼ 7, range 18–57 years). Subjects were screened for

relevant contraindications: neuromuscular or cardiac disor-

ders, peripheral neuropathy, history of trauma or surgery to

the dominant hand or leg, current medication and pain,

history of epilepsy, diabetes, pregnancy or knowledge of

TENS treatment. Six subjects were excluded (n ¼ 1

epilepsy, n ¼ 1 current medication, n ¼ 1 pregnancy, n ¼

3 TENS familiarity) and additional subjects were recruited

as replacements. The experimental procedure was explained

to each subject who then signed a consent form. Subjects

were randomly assigned to one of the eight experimental

groups using computer generated random number lists.

Groups were similar for gender (n ¼ 30, 15 males and 15

females) age, and MPT at baseline. This was confirmed by a

one-way analysis of variance (ANOVA) for pre-treatment

mean MPT (P ¼ 0:19) and Kruskal Wallis test for age

(P ¼ 0:59) showing no significant differences.

2.2. Equipment

Mechanical pain was induced using a pressure algometer1

with a flat circular metal probe dressed in several layers of

lint and measuring 1.1 cm in diameter. Force was displayed

L.S. Chesterton et al. / Pain 99 (2002) 253–262254

1 Salter Abbey Weighing Machines Ltd, England.

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digitally in increments of 0.1 N. The algometer was

mounted vertically on a purpose-built calibrated iron

stand2 to enable force to be applied at a controlled and

steady rate of 5 N/s. The reliability of results obtained

using a pressure algometer have been reported elsewhere

(Nussbaum and Downes, 1998; Antonaci et al., 1992;

Fischer, 1987).

Electrical stimulation was generated via a dual channel,

portable TENS unit3 which was calibrated using an oscillo-

scope4 according to Walsh (1997). An asymmetrical bipha-

sic waveform was delivered through 5 cm2 self-adhesive

carbon rubber electrodes.5 Frequency was set at 4 or

110 Hz, pulse duration at 200 ms, and intensity was

increased to the subjects’ verbal report of ‘strong but

comfortable’ or ‘to tolerance’ levels, depending on group

allocation. These choices represent intensities traditionally

associated with the conventional and AL-TENS modes

previously described.

2.3. Subject preparation

Subjects were seated in a comfortable upright position

and the stimulation sites were prepared with alcowipes.

These sites were termed segmental and extrasegmental to

the location of the MPT measurement point. The segmental

site was the lateral border of the forearm of the dominant

arm over the distribution of the superficial radial nerve,

which innervates the MPT measurement site and corre-

sponds to acupoints large intestine 6 (LI6) and lung 7 (Lu

7). This site has been used in previous studies (McDowell et

al., 1999; Walsh et al., 1995, 1998) and was chosen for the

following reasons: (a) to reflect clinical stimulation of

acupoints, (b) allow stimulation within the same dermatome

as experimental pain site, and (c) to keep the experimental

pain site clear for measurement purposes. The extrasegmen-

tal site was the area anterior and just inferior to the fibula

head over acupuncture point gall bladder 34 (GB34). A

standard ‘sharp/blunt’ skin sensation test was performed

using neurotips at each site. Two electrodes from a single

channel were then attached to the segmental site, (cathode

proximal) and with electrodes from the second channel

applied such that the cathode was placed directly over

GB34, on the dominant leg, with the anode 1 cm distal.

All subjects, regardless of group, had electrodes placed at

both stimulation sites to maintain blinding.

2.4. TENS procedure

Table 1 provides a summary of the parameter combina-

tions and the active electrode channels for all eight experi-

mental groups. To maintain blinding of the subjects, the

small lights on the TENS unit that indicate the active chan-

nel were covered with tape. To maintain blinding condi-

tions, two experimenters took part. Experimenter 1 was

solely responsible for all aspects of TENS applications.

Before stimulation, subjects in TENS groups 1, 2 and 3

(4 Hz/200 ms/‘to tolerance’ intensity) were told that they

would feel strong ‘pricking or tapping sensations’ beneath

some or all of the electrodes and might experience muscle

contractions around their thumb, fingers, knee or leg. The

intensity was increased until it reached the maximum toler-

able level for the subject, which was described as very

strong and uncomfortable. Subjects in TENS groups 4, 5

and 6 (110 Hz/200 ms/‘strong but comfortable’ intensity)

were told that they would feel a buzzing or tingling sensa-

tion beneath one or both of the electrodes, and this would be

increased until it reached a ‘strong but comfortable’ level.

Subjects in the sham TENS group, were told that some

forms of TENS were imperceptible and, therefore, they

may or may not feel a sensation. The battery in the TENS

unit was inserted the wrong way round to allow the unit to

be visibly switched on and the intensity turned up, but with

no current flowing. Subjects in the control group were

informed that, although electrodes were attached to main-

tain blinding of experimenter 1, the machine would not be

switched on and no TENS would take place.

The 10-min stimulation periods were timed from the

point when the intensity of the TENS had reached the appro-

priate level for the experimental group. After the first, third,

fourth, sixth and eighth minute of stimulation in each 10-

min application, subjects were asked if the sensation had

faded, if so, the intensity was increased to maintain the

specified level. Stimulation was delivered for a total of

L.S. Chesterton et al. / Pain 99 (2002) 253–262 255

2 Salter Abbey Weighing Machines Ltd, England.3 TPN 300, Physio-Med Services, Glossop, Derbyshire, UK.4 Fluke 867B Graphical Multimeter.5 PALS Electrode TPN 40, Physio-Med Services, Glossop, Derbyshire,

UK.

Table 1

Summary of the eight experimental group parameters

Group Frequency (Hz) Pulse duration (ms) Stimulation site Stimulation site identifier Intensity

TENS 1 4 200 Radial nerve 1 GB34 Combination To tolerance

TENS 2 4 200 Radial nerve only Segmental To tolerance

TENS 3 4 200 GB34 only Extrasegmental To tolerance

TENS 4 110 200 GB34 only Extrasegmental Strong but comfortable

TENS 5 110 200 Radial nerve only Segmental Strong but comfortable

TENS 6 110 200 Radial nerve 1 GB34 Combination Strong but comfortable

Control – – Both inactive None N/A

Sham – – Both inactive None N/A

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30 min, in three blocks of 10 min. Subjects were monitored

for a further 30 min after the end of the stimulation period.

2.5. Mechanical pain threshold measurement procedure

The MPT measurement point was marked 3.5 cm distal

from the proximal edge of the anatomical snuffbox in the

direction of the muscle belly of the first dorsal interosseous

muscle, an area innervated by the superficial radial nerve. A

3.5 cm card measure was used to standardise marking of this

measurement.

Experimenter 2 was responsible solely for MPT measure-

ments and was blind to the subject’s experimental group

allocation. Subjects were instructed in the application of

the algometer and given a demonstration by the experimen-

ter. Subjects then underwent two practice MPT measures

using their non-dominant hand, during which they were

coached in differentiating their report of tactile and painful

stimulus. MPT was taken as the amount of pressure required

to elicit a sensation of pain distinct from pressure or discom-

fort (Fischer, 1987). Subjects were asked to say ‘stop’

immediately when a sensation of pain, distinct from pres-

sure or discomfort, was felt. The algometer was applied

perpendicularly to the skin and lowered at a rate of approxi-

mately 5 N/s until MPT was reached as indicated by the

subjects’ verbal report. At this point the experimenter

immediately retracted the algometer. Two measures were

taken at 10 min intervals over a 60-min period, giving a total

of 14 measures. The first MPT measurement was made

before switching on the TENS unit and used as a baseline

figure. Experimenter 2 left the room after each MPT

measurement was completed. The interruption to TENS

stimulation at each measurement point lasted approximately

45–60 s.

3. Data analysis

The lower of the two MPT readings at each measurement

point was used for analysis. To standardise the data across

subjects, MPT difference scores were calculated

(MPT diffi ¼ MTPtimeðiÞ 2 MPTbaseline). A positive differ-

ence score indicates a hypoalgesic effect, and negative

scores indicate hyperalgesia. These scores were analysed

using a two-way ANOVA with repeated measures on the

dependent variable of MPT, and one-way ANOVA with

post hoc multiple comparisons, to identify differences

between groups at each time point. Statistical significance

was set at 0.05. Assumptions underlying the tests were

checked and did not change the significant findings. Data

were analysed using the Statistical Package for Social

Scientists (SPSS, Version 10) for Windows.

4. Results

Table 2 summarises the mean MPT difference scores (^

standard error of the mean) at each time point for each

experimental group. The two-way ANOVA with repeated

measures revealed significant differences across the two

main effects of group (P , 0:0005), and time

(P , 0:0005), and also for the interaction effect

(P , 0:0005). Further one-way ANOVA with post hoc

multiple comparisons (Bonferroni adjustment) identified

the differences, which occurred between groups at each

time point. Table 3 summarises the statistically significant

results. It is notable that whilst several groups achieved

statistically significant differences with both the control

and sham TENS groups during stimulation, only TENS

group 3 (4 Hz/200 ms/‘to tolerance’ intensity/extrasegmen-

tal stimulation) achieved significant differences during the

post-stimulation period. TENS group 3 also demonstrated

significant differences throughout the post-stimulation

period compared with TENS group 4 (110 Hz/200 ms/

‘strong but comfortable’ intensity/extrasegmental).

Fig. 1 summarises MPT difference scores over time for

TENS groups 1, 2 and 3 (4 Hz/200 ms/to tolerance inten-

sity), the sham TENS group and the control group. Within

the active TENS groups, a rapid and increasing hypoalgesic

effect is observed for TENS group 1 (combination site

stimulation), and TENS group 3 (extrasegmental stimula-

tion). The maximal mean MPT difference scores were

12.75 N (P , 0:0005control, P ¼ 0:001sham) and 13.72 N

(P , 0:0005control, P , 0:0005sham), respectively. During

the post-stimulation period, an initial, yet slight, fall in

hypoalgesic effect is observed in TENS group 3 (from

L.S. Chesterton et al. / Pain 99 (2002) 253–262256

Table 2

Mean MPT difference scores (standard error of mean) for each group at each time point (n ¼ 30) (all scores are expressed in Newtons)

Group Stimulation Post-stimulation

10 min 20 min 30 min 40 min 50 min 60 min

TENS 1 5.62 (1.04) 10.20 (1.36) 12.75 (1.67) 7.09 (1.26) 6.71 (1.59) 6.17 (2.0)

TENS 2 2.84 (1.77) 5.14 (1.77) 6.31 (2.21) 7.10 (2.21) 7.10 (2.26) 5.67 (1.94)

TENS 3 8.20 (1.62) 10.71 (1.92) 13.72 (2.27) 12.08 (2.30) 11.29 (2.30) 11.38 (2.45)

TENS 4 3.26 (1.14) 5.41 (1.45) 4.81 (1.90) 2.12 (1.26) 1.71 (1.48) 1.77 (1.76)

TENS 5 5.89 (1.73) 11.50 (1.90) 13.27 (2.32) 5.66 (1.56) 6.32 (1.57) 4.67 (2.07)

TENS 6 6.79 (1.33) 9.60 (1.98) 10.20 (1.73) 8.11 (2.20) 6.89 (2.06) 6.57 (2.32)

Control 20.40 (1.04) 20.047 (1.37) 20.32 (1.49) 0.13 (1.68) 20.64 (1.41) 2.02 (1.61)

Sham TENS 3.72 (1.28) 4.02 (1.84) 1.38 (1.76) 2.00 (1.52) 2.83 (1.64) 3.27 (1.68)

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13.75 N to 12.08 N). For the remainder of the period, a

relatively constant and high level of hypoalgesia is main-

tained (minimum 11.29 N, P , 0:0005control, P ¼ 0.024sham,

P ¼ 0:005TENS 4). Conversely, for TENS group 1 (combina-

tion site stimulation), when stimulation ceased a rapid and

sharp fall in MPT was seen in the first 10-min period (to

7.09 N P ¼ 0:19control), which continues to fall, although a

level of hypoalgesia above the baseline (6.17 N) was still

evident at the 60-min measurement point. Changes in TENS

group 2 (segmental stimulation) and the sham TENS group

were small and did not achieve statistically significant

differences with respect to the control group. Within the

control group MPT changed little over the course of the

experiment (maximum MPT ¼ 2:02 N) demonstrating the

stable, yet sensitive to experimental manipulation, nature

of this experimental measure.

Fig. 2 summarises MPT difference scores over time for

TENS groups 4, 5 and 6 (110 Hz/200 ms/‘strong but

comfortable intensity’), the sham TENS group and control

groups. A large and rapid hypoalgesic effect for TENS

group 5 (segmental stimulation), and TENS group 6

(combination site stimulation) were observed. The

maximal mean MPT difference scores measured were

13.27 N (P , 0:0005control, P , 0:001sham) and 10.2 N

(P ¼ 0:005control, P ¼ 0:042sham), respectively. However,

during the post-stimulation monitoring period, a large fall

in hypoalgesic effect is observed at the 40-min measure-

ment point for both these groups (TENS 5 MPT ¼ 6:66 N

and TENS 6 MPT ¼ 8:11 N) with no significant differ-

ences observed between these groups and the sham or

control groups. TENS group 4 (extrasegmental stimulation)

showed a small rise in MPT (5.41 N maximal) during

stimulation which is similar to that of the sham TENS

group (4.02 N maximal); TENS group 4 did not show

significant differences to the control group.

For comparison, Fig. 3 shows the profiles of each TENS

group that achieved statistically significant differences with

respect to the control group. Of note is the similar pattern of

changes during the stimulation period and the comparable

maximal levels of hypoalgesia achieved regardless of differ-

ent parameter selection (range 10.2–13.73 N). There were

no significant differences between active TENS groups

shown in this figure (Fig. 3). The important difference

between the groups was seen in the post-stimulation period

where only TENS group 3 (4 Hz/200 ms/to tolerance inten-

sity/extrasegmental) showed a sustained hypoalgesic effect

(P , 0:0005control).

5. Discussion

The purpose of this study was to determine the effect of

different combinations of TENS frequency, intensity and

stimulation site on the MPT in healthy subjects. The results

illustrate the hypoalgesic potential of several different

TENS parameter combinations and emphasise the impor-

L.S. Chesterton et al. / Pain 99 (2002) 253–262 257

Table 3

Summary of post hoc tests showing significant differences between groups at each time point

Phase Time (min) Group Comparison group Mean difference between groups Standard error P value

Stimulation 10 Control TENS 3 28.60 2.02 0.001

TENS 6 27.19 2.02 0.013

Stimulation 20 Control TENS 1 210.67 2.42 0.000

TENS 3 211.18 2.42 0.000

TENS 5 211.97 2.42 0.000

TENS 6 210.07 2.42 0.001

Stimulation 30 Control TENS 1 213.08 2.74 ,0.0005

TENS 3 214.05 2.74 ,0.0005

TENS 5 213.59 2.74 ,0.0005

TENS 6 210.52 2.74 0.005

30 Sham TENS 1 211.37 2.74 0.001

TENS 3 12.34 2.74 ,0.0005

TENS 5 11.89 2.74 0.001

TENS 6 28.82 2.74 0.042

30 TENS 4 TENS 3 28.92 2.74 0.037

Post-stimulation 40 Control TENS 3 211.95 2.55 0.000

Sham TENS 3 210.08 2.55 0.003

TENS 4 TENS 3 29.96 2.55 0.004

Post-stimulation 50 Control TENS 3 211.92 2.50 0.000

Sham TENS 3 28.46 2.50 0.024

TENS 4 TENS 3 29.58 2.50 0.005

Post-stimulation 60 Control TENS 3 29.36 2.87 0.036

TENS 4 TENS 3 29.61 2.87 0.027

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L.S. Chesterton et al. / Pain 99 (2002) 253–262258

Fig. 2. MPT difference scores for 110 Hz/200 ms/strong but comfortable intensity intervention groups, sham and control (n ¼ 30 per group) (W Significantly

different from control group P , 0:05) – See text for details.

Fig. 1. MPT difference scores for 4 Hz/200 ms/noxious intensity intervention groups, sham and control (n ¼ 30 per group). (W, significantly different from

control group P , 0:05, V, significantly different from sham TENS P , 0:05) See text for details

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tance of stimulation site in the hypoalgesic effect obtained.

Available literature provides directly comparable, albeit

limited, experimental evidence with which to evaluate

these results; however, a series of studies using large clinical

samples from University of Texas provides some compara-

tive data.

Studies by Wang et al. (1997), Chen et al. (1998) and

Hamza et al. (1999) have all used a clinical model of

acute post-operative pain to investigate the effects of manip-

ulating stimulation intensity, site and frequency. Each study

used a similar protocol with 100 women who had undergone

lower abdominal surgery. The common design was of a

randomised single blind, sham controlled study with experi-

mental groups of 25 subjects. Thirty minutes of stimulation

at two-hour intervals (when patients are awake) was

applied. Stimulation was used in conjunction with other

standardised pharmacological analgesic interventions. The

initial study by Wang et al. (1997), reported results for a

control group to establish a baseline effect for analgesics

alone with no stimulation intervention. In each study, trans-

cutaneous acupoint electrical stimulation (TAES) ‘dense-

disperse’ stimulation (an alternating frequency between 2

and 100 Hz every 3 seconds) was used, a combination

developed by the reporting authors. The sample size for

the initial study was calculated at a power of 80% to identify

a 30% reduction in the post-operative opioid analgesic

requirements as the dependent variable. This variable is

used for discussion here although other dependent variables

are reported.

The first study by Wang et al. (1997) investigated the

effect of varying intensity whilst stimulating the Hegu

acupoint (first interosseous web space – LI4) and the

abdominal incision site simultaneously. The results showed

that the efficacy of stimulation was dependent upon inten-

sity. This was indicated by a .50% decrease (P , 0:05) in

the total post-operative analgesic requirement when a stimu-

lation level of 9–12 mA was used as opposed to 4–5 mA.

Whilst the effect of the mixed-frequency (2–100 Hz) stimu-

lation does not allow a direct comparison with our results,

we also showed that stimulation at a combination of two

sites was intensity-dependent, but for very different reasons.

High frequency, low intensity stimulation was shown to be

just as effective as low frequency, high intensity stimulation.

However, in addition we found that there was no additional

hypoalgesic benefit from stimulating at two sites over and

above the level of hypoalgesia observed at single site stimu-

lation. Indeed the low frequency, high intensity, combined

stimulation group showed that the post-stimulation effects

of extrasegmental stimulation alone were negated. Never-

theless, some consensus regarding mixed frequencies

requiring high intensity stimulation is supplied by Johnson

et al. (1992). In a double blind, sham-controlled study, using

L.S. Chesterton et al. / Pain 99 (2002) 253–262 259

Fig. 3. MPT difference scores for intervention groups. All groups depicted in this figure showed significant differences over time compared with the control

group during the stimulation period, however, only group 3 maintained such differences during the monitoring period (P , 0:005). In addition, at the 10-min

point only groups 3 and 6 were significantly different from the control group, indicating a rapid onset of analgesia (n ¼ 30 per group).

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an experimental cold pain model, 60 healthy subjects were

randomised to five experimental groups. Prolonged post-

stimulation hypoalgesia compared with a sham group was

only reported when ‘burst’ TENS (frequency of 2.3 Hz with

bursts at 80 Hz) was applied for 30 min at a distant, but

myotomally-related area stimulating at the highest tolerable

intensity. This combination of parameters showed greater

hypoalgesic effects than ‘burst’ TENS applied at the same

site but at lower intensity levels and also conventional

TENS applied segmentally. The authors, however, noted

considerable individual variation in this response, which

was also previously reported in a study from the same

group (Ashton et al., 1984) and in the results presented

here. Johnson et al. (1992) did not investigate these reported

effects using combined stimulation sites.

The effect of manipulating stimulation site is reported by

Chen et al. (1998). Using the clinical model noted above,

100 female subjects were randomly assigned to one of four

treatment regimes, including: (1) TENS applied at the level

of the surgical incision; (2) bilateral acupoint – TAES at the

Zusanli (ST36) acupoints; (3) non-acupoint – TAES at the

shoulder, and (4) sham – TAES at acupoint ST36. Mixed-

frequency (2/100 Hz) stimulation with intensity between 9

and 12 mA was applied. The total opioid requirements

measured in the first 24 h post-surgery in both the dermato-

mal and acupoint stimulation groups were decreased by

between 35 and 39% when compared with the sham group

and non-acupoint stimulation groups. Using this and other

measured indicators, the authors concluded that dermatomal

and acupoint stimulation were equally effective and both of

these positions were more effective than the non-acupoint

(shoulder) location. The results of our study agree with this

to some extent, in so much as the segmental and extraseg-

mental sites were shown to be equally effective in achieving

hypoalgesic effects, but this was dependent upon different

combinations frequency and intensity parameters. Results

from our study also contrast with Chen et al. (1998) in

that segmental stimulation using low frequency/high inten-

sity parameters was shown to be ineffective. Once again,

however, the mixed frequency used by Chen et al. (1998)

restricts the ability to interpret the role of frequency in the

measured outcome. A tentative conclusion that can be

reached from the study by Chen et al. (1998) and the current

study is that stimulation site is an important determinant to

achieve maximal hypoalgesic effects.

Based on the previous results from the same group,

Hamza et al. (1999) investigated the effects of stimulation

frequency at a segmental site alone. In this case patients

were randomly assigned to four groups as follows: low-

frequency (2 Hz) TENS; high frequency (100 Hz) TENS;

mixed-frequency (2–100 Hz) TENS and sham TENS.

Stimulation was given around the surgical incision site at

a high intensity of 9–15 mA. The pulse width was reported

to alter automatically within a range of 0.2–0.6 ms. The

results showed that mixed frequency stimulation reduced

opioid requirements by 53% compared with the sham

group, with both low (2 Hz) and high (100 Hz) frequencies

producing decreases of smaller magnitude (32 and 35%,

respectively). Results from our study also showed low

frequency (4 Hz) high intensity stimulation to be less effec-

tive when applied segmentally, at least when compared with

other parameter combinations. Clinically, high frequency,

high intensity combinations are rarely used due to patient

discomfort, but it is of interest that the mixed frequency,

high intensity combination proved most effective. In this

instance, however, no comparative low intensity stimulation

groups were used and stimulation was only at a segmental

non-acupoint site. In making comparisons with these

studies, it is important to consider that physiological

responses to electrical stimulation in clinical situations of

acute pain may not be directly comparable to an experimen-

tal model of pain in healthy subjects, and all conclusions

must be viewed in this light.

With regard to the results from this study, some physio-

logical support can be suggested. The hypoalgesic effect of

high frequency, low intensity segmental parameter combi-

nations, which are not repeated extrasegmentally, is in

agreement with the pain modulation effects proposed within

the pain gate theory (Melzack and Wall, 1965). Similarly,

the prolonged hypoalgesic effects of extrasegmental, low

frequency stimulation suggest some form of systemic

response in line with the endogenous opioid response.

However, the rapid hypoalgesic onset would appear to be

inconsistent with the effect of this slow responding system,

as suggested by Sjolund and Eriksson (1976). It could be

argued that this mechanism may be responsible for the post-

stimulation hypoalgesia (Chen and Han, 1992). Alternative

mechanisms may also be involved at many levels within the

CNS. Whilst it is not clear which systems are involved, or

how they are co-ordinated within the individual, possibili-

ties include the ‘diffuse noxious inhibitory control’ system

proposed by Le Bars et al. (1979a,b) and the inhibition of

the spinothalamic tract cells at a spinal cord level as a

response to activation of the Aa, Ab and Ad fibres, a theory

proposed by Chung et al. (1984). Excitation of a sympa-

thetic response may also alter the afferent input to the

CNS (Ito et al., 1984) with the autonomic response extend-

ing widely to viscera, joints and skin (Shacklock, 1999).

Wright and Sluka (2001) have also suggested that motor

facilitation and sympathetic excitation are consistent with

activation of the lateral periaqueductal grey matter, which

may evoke analgesia as part of a defence response (Willis

and Westlund, 1997). The initial hypoalgesia, which is not

sustained post-stimulation in the low frequency/low inten-

sity, combined site stimulation group (TENS group 1), may

suggest a peripheral blocking effect which overrides this

systemic response. Although the contribution of altered

peripheral nerve activity to the hypoalgesic effect proposed

by Ignelzi and Nyquist (1976) has been questioned by Janko

and Trontelj (1980), other authors strongly suggest a periph-

eral component to TENS mediated hypoalgesia, which may

be regulated by central mechanisms (Walsh et al., 1998;

L.S. Chesterton et al. / Pain 99 (2002) 253–262260

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Levin and Hui-Chan, 1993; Francini et al., 1981). Further

studies, which measure such physiological responses, are

required to identify the mechanisms involved. Future

research is also required to investigate the effects of combin-

ing different frequency and intensity parameters.

In summary, the data presented here have confirmed that

parameter combinations including stimulation site may play

an important role in the maximal hypoalgesic effect attained

and in post-stimulation hypoalgesia, within an experimental

model of pain. It is therefore possible that popular TENS

modes used clinically may not always produce optimal

hypoalgesic effects. Further research into stimulation site

and intensity levels is therefore required.

Acknowledgements

The authors thank Professor J. Sim for his valuable

comments to the final version of the manuscript. Funding

for the experiment and equipment was provided by Coven-

try University School of Health and Social Sciences.

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