Pa&, 47(1991)157-162

157

© 1991 Elsevier Science Publishers B.V. All rights reserved 0304-3959/91/$03.50

PAIN 01860

Comparative effectiveness of different stimulation modes in relieving pain. Part II. A double-blind controlled long-term clinical trial M e t i n T u l g a r ", Francis M c G l o n e a, David B o w s h e r a a n d J o h n B. Miles b Pain Research Institute, Pain Relief Foundation, Walton Hospital, Licerpool L9 1AE (U.K.), and b Department of Neurological Science, University of Liuerpool, Walton Hospital, Liuerpool L9 1AE (U.K.)

(Received 1 November 1990,revision received 11 February 1991, accepted 1 March 1991)

Summary Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms - frequency modulation and burst - rather than conventional continuous mode. To assess whether long-term therapeutic effects validate the immediate test results, this trial was performed in 14 patients with 21 pain conditions. Considering the results of the pilot study, the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were randomly delivered to each patient who was blind to the modes of stimulation for 20 min. A second observer assessed the pain scores using visual analogue scales. The stimulation modes employed were: (1) conventional continuous stimulation (continuous pulses with a constant frequency of 70 Hz), (2) burst stimulation (80 msec long trains of pulses, each train consisting of 8 pulses, with an internal frequency of 90 Hz repeated 1.3 times a second), (3) high-rate frequency modulation, H R F M (continuous pulses changed from 90 Hz to 55 Hz over 90 msec, 1.3 times a second), (4) low-rate frequency modulation, LRFM (continuous pulses changed from 60 Hz to 20 Hz over 90 msec, 1.3 times a second). After the test treatment of 4 sessions in the clinic, depending on the pain scores and duration of pain relief recorded, the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home, under our supervision, for 3 months. Fourteen pain conditions out of 21 (66%) responded well to the therapy; the majority preferred was the H R F M and burst-type stimulation. These results validate the initial testing of different stimulation modes before assessing long-term stimulation therapy. Key words: Transcutaneous electrical nerve stimulation; Stimulation modes; Stimulation parameters

Introduction Many clinical studies of transcutaneous nerve stimulation (TNS) are poorly controlled and lack any longterm follow-up assessment. Up to 70% of the patients may initially respond well to TNS but, by the end of first year, this rate drops to around 30% [3]. To improve the efficacy of the treatment, some studies on stimulation parameters such as pulse width, pulse

Correspondence to: Metin Tulgar, Ph.D. Researcher, Pain Relief Foundation, Walton Hospital, Rice Lane, LiverpoolL9 IAE, U.K.

shape, frequency, intensity, polarity and signal patterns have been performed [1,8,13,21]; however, much work is still needed in this field. Most of the studies have been carried out with conventional continuous mode of stimulation, and differential effects of different frequencies have been reported [2,7,16]. Eriksson et al. [6] and Connelly et al. [5] also tested short bursts of pulse trains and observed differential effects. Part I of our earlier pilot study [19] has shown that patients treated with TNS prefer modulated stimulation modes, such as frequency modulation and burst rather than conventional continuous stimulation. The purpose of this study is to assess whether the long-term therapeutic effects validate the immediate test results.

158

Fourteen patients with 21 pain conditions participated in this trial. Eight patients with 14 pain conditions rcsponded to the treatment, whilst 6 will] 7 pain conditions did not. Four out of 7 patients with low-back pain ( L B P ) b e n e f i t t e d from frequcncy-moduhltcd stimulation, in which continuous pulses changed from 90 Hz to 55 Hz over 90 msec (high rate frequency modulation, ttRFM). One patient found constant stimulation more effective. Three out of 4 patients with sciatica responded well to burst-type stimulation. One patient with brachial plexus syndrome (BPS) preferred H R F M stimulation. One patient suffering from postherpctic neuralgia (PHN) found frequency-modulated stimulation in which continuous pulses changed from 60 Hz to 20 Hz over 911 msec (low rate lYequency modulation, LRFM) to be effective, and another suffering from post thoracotomy scar pain ( H ' S P ) benefittcd from burst stimulation. A chronic tension headachc ( C I H ) sufferer also found the burst mode of stimulation most effective.

I,\BII I I).VI-A (IN PATIIINI'S P,,\RII('II)A'I'IN(i IN IIII. IRI,\I t BI ) : h)w h a c k pain: BPS :: hlacl'dal plexus s_'~lldrolllC: I'1 IN : posl herpetic n e u l a l g i a : ('PSP central post-stroke pain: I>I'SP pont IholaCotOlll 3 SCZll pztiI/: l'hl phalltOnl limb pain: ( " I l l chr(mit: It: II ~;iO[I h e a d a c h e .

Pali¢in characteristics Paticnl * (N)

Age * *

Sex

Diagnosis * :~:+:

I 2 3 4 g o

70 37 70 55 54 50

F M M M 1M

7 S t)

ol 511 511

M M F

I(1

75 53

F

II

I,BP + sciatica BPS LBP ~ sciatica Pl tN IBP LBP~- pare t)l r h e u m a t i c origin in both lower lugs aIld arms CPSP PTSP ('ervical spondylosis LBP Phi. pain in lhe left leg Spasm pain m both

12

70

M

13 14

4t 25

F F

F

h ) w e r legs

Method In the earlier pilot study, patients treated with TNS reported that burst and frequency-modulated stimulation were more effective in relieving their pain [19]. Considering these results, the test stimulator was modified; various frequency modulation rates (changes of 10, 25, 50, and 10(l%) and constant frequencics of 1.3, 3, 5, 10, 30, 50, 70 and 90 Hz were included. The modified version of the test stimulator was employed in the long-term trial. Fourteen patients participated in this trial. Some of these patients were suffering from more than 1 pain, e.g., low-back pain associated with sciatica. For thcse patients, pain conditions were assessed separately. In all, 21 pain conditions were involved. Data about these patients is given in Table 1. This study was performed in 2 phases: (1) test treatmcnt and (2) follow-up treatment. After suitable patients had been selected for TNS, they werc invited to the clinic on 4 separate days. On each day, they were treated with a different stimulation mode. Four stimulation modes were tried during the test phase: conventional constant stimulation, burst stimulation, high-rate frequency-modulated stimulation ( H R F M ) and low-rate frequency-modulated stimulation (LRFM). In conventional mode, continuous pulses with a constant frequency of 70 Hz were administered. Burst stimulation consisted of 80 msec long trains of pulses. each train consisting of 8 pulses, with an internal frequency of 90 Hz repeated 1.3 times a sccond. During H R F M stimulation, frequency changed between 90 Hz and 55 Hz over 90 msec, 1.3 times a second. This is similar to the frequency modulation employed in the

LI~P ~- pain in the left s h o u l d e r and left leg due to a r a c h n o d i t i s I.BP + sciatica [BP ~ ('TII

N u m b e r of patients: 7 male and 7 female. ** Age: 3 6 - 7 6 (mean: 54). :~ * * N u m b e r of diagnoses: 21.

pilot study [19]. In L R F M stimulation, frequency changed from 60 Hz to 20 ttz over 90 msec, again 1.3 times a second. The pulse repetition frequency was kept at 1.3 Hz as recommended by Omura [13], who advocated that the stimulation frequency should be synchronized with the patient's heart rate in order to avoid micro-circulatory disturbances. While not necessarily agreeing with the logic he uses, which would require complex feed-back circuitry to substantiate, we decided to folk)w this recommendation. Plotted outputs of the stimulator for each mode arc shown in Figs. 1, 2, 3, 4 and 5. The electrodes were placed for optimal distribution of paraesthesia and optimal pain relief in all cases. The order of stimulation modes was chosen randomly. The patients were blind to the modes of stimulation. Thc intensity of stimulation was half-way between the stimulation perception threshold and tolerance level for each patient [11]. Each session lasted 20 rain. In order to minimize any undesirable electrolytic phenomemt during the stimulation [13], the polarity of the stimulator output was reversed in the middle of each session. While doing this, in order to avoid electric shock by the

159 100 v / d l v 2 0 0 pls/dlv f

5 0 0 v/dlv

i

200 ms/dw

i

i

CHI4444LLLL ~CHI CH1

CH1

f

I

I

I

I

[

I

I

I

]

Fig. 1. A single pulse applied in all stimulation modes.

500v/dlv

200 ms/dlv

CHI

CH1

I

I

=I

I

I

I

I

I

I

k

Fig. 2. Output of the stimulator when set for the conventional constant mode of stimulation.

5 0 0 v/dtv I

i

]

]

i

i

i

i

i

iI

Fig. 4. Output of the stimulator when set for the HRFM stimulation.

transient high voltage, before changing the polarity the amplitude was lowered to zero and after the polarity was changed the amplitude was again increased to therapeutic level. Visual analogue scales (VAS) were used to assess the pain intensity. A second observer asked the patient to rate the pain on VAS before beginning treatment and within 5 min after termination of stimulation. Pain relief was assessed on completion of the stimulation because some patients reported varying amounts of relief during the period of treatment. Pain scores and duration of the pain relief, if obtained, were recorded. After the test treatment of 4 sessions in the clinic, depending on the pain scores and the duration of pain relief recorded, the most effective stimulation mode was determined for each patient. Patients who had pain relief only during stimulation were excluded. A portable stimulator preset appropriately for the most effective mode was then given to the patients to use at home, under our supervision, for 3 months The pa-

200 ms/dw i

i

r

5 0 0 v / d l v 2OO m s / d r v I

i

i

i

r

e

t

i

I

k

1

t t_LL/ LL

CH1

_CH1

iCHI

CH1 !

J I

I

I

I

I

I

I

l

I

I]

Fig. 3. Output of the stimulator when set for the burst mode of stimulation.

I

I

I

I

I

I

I

Fig. 5. Output of the stimulator when set for the LRFM stimulation.

1611

TABLE II RESULTS OF TEST T R E A T M E N T C = conventional constant stimulation: B - burst stimulation; HRFM = high-rate frequcncy modulation: I.RFM tkm. Patient (N)

1 I 2 3 3 4 5 0 6 6 7 8 9 9 10 t1 12 12 13 13 14 14

Diagnosis

LBP Sciatica BPS LBP Sciatica PHN LBP LBP Leg pain Arm pain CPSP PTSP Cerv. spondy. LBP PhL pain Leg spasm pain Shoulder pain LBP LBP Sciatica LBP CTH

Pain relief (VAS) pre and post stimulation *

Duration of pain relief (h) after stimulation

low ratc frequency moduht-

Effective mode

c~; Reduction in VAS

C

B

HRFM

LRFM

C

B

HRFM

LRFM

27-11 32-15 85-63 50-50 50-50 74-71) 75-56 18-10 20-10 18-12 50-511 47-4 95-25

11-8 17-2 92-36 76-82 76-88 64-59 86-26 42-0 40-0 35-0 50-50 t110-0 35-/I

39-18 39-18 86-28 52-52 40-40 56-43 86-69 36-9 25-4 28-1/) 48-43 46-6 60-10

79-32 75-40 84-59 82-711 8/)-72 75-66 86 16 25-0 20-0 20-1/ 50-40 4/) 5 29-11/

4 3 4.5

5 6 5

53.8 88.2 67

4 I 1 1.5 1.5

LRFM

12

HRFM B B

1(10 1//0 100

5.5 8

t~ 6

45 4 5 l 1 6 I 1.5 1 I 1.5 7 5

HRFM B ItRFM

3 1 1 l l

6.5 ~ 6 4 2 1.5 2 2 1 7 8

B 13

100 100

56-11/ 13-0 79-79

58-12 60-4 89-80

50-0 14 8 80-81/

55-15 19-/I 77-77

6 3

5 3 3

8 2

5 8

HRFM

1011

35-17

62-47

5/I-43

50-44

11.5

/1.5

11.5

47-28 60-10 65-20 80-80 82-25

51-31 80-20 70-0 82-15 95-0

50-47 40-20 70-10 40-0 79-16

55-45 50-10 60-20 77-18 82-25

11.5 2 5 7 12

/1.5 3.5 3.5 12 9

3 2.5 6 3

5 3 5

**

**

C B HRFM B

-- ** 83.3 100 100 t00

* Some patients reported varying amounts of pain relief during the period of treatment. ** These patients failed to get prolonged pain relief in long-term treatment.

tients were asked to record pain scores and duration of pain relief on proforma charts.

Results

Fourteen patients participated in this trial. Seven patients had more than 1 pain condition; 3 had low-back pain associated with sciatica; 1 had low-back pain with leg and arm pain of rheumatic origin; 1 had low-back pain and cervical spondylosis; 1 had low-back pain and tension headache. The total number of pain conditions involved was 21. Eight patients with 14 pain conditions responded to the treatment during and following the stimulation, whilst 6 with 7 pain conditions did not. The results of test treatment are shown in Table II. As seen from this table, 4 out of 8 patients with LBP benefitted from H R F M stimulation and 1 found constant stimulation more effective. Three out of 4 pa-

tients with sciatica responded to burst stimulation. One patient suffering from brachial plexus syndrome preferred H R F M stimulation while another patient with post thoracotomy scar pain benefitted from burst stimulation. One patient with post-herpetic neuralgia (PHN) found L R F M stimulation more beneficial. One patient with chronic tension headache (CTH) benefitted from burst-type stimulation. Four patients with 6 pain conditions (marked with ** in Table II) found the stimulation beneficial during the test period and were involved in long-term treatment. However, after a while they failed to get prolonged relief and were excluded. Table III shows the details of long-term treatment. The same stimulation modes were employed with success for 3 months for the 8 patients with 14 pain conditions who had promising results during the test period. All of these patients except the one with PHN continued to use the portable stimulators to manage their pain and are not taking analgesic medication on

161 T A B L E II1 RESULTS OF LONG-TERM TREATMENT Follow-up treatment Patient (N)

1 1 2 4 6 6 6 8 9 9 13 13 14 14

Diagnosis

Stimulation mode employed

% reduction in VAS (mean)

Duration of pain relief after stimulation (h) (mean)

LBP Sciatica BPS PHN LBP Pain in both legs Pain in both arms PTSP Cervical spondylosis LBP LBP Sciatica LBP CTH

HRFM B ttRFM LRFM HRFM B

58.5 42.6 60.3 55 67.6 98.8

8.6 4.4 4.9 5.5 2.9 1.8

B

96.9

1.8

B B

71.9 91.5

8.3 11

HRFM C B HRFM B

81.3 72.3 69.2 96.8 97.1

8.3 4.3 4 !l l 1.6

which they were dependent before stimulation. Two of these patients (numbered 1 and 9) started to use the portable stimulator at home twice a day, and treatment frequency was gradually decreased. After 3 months, they now rarely use the stimulator.

Discussion

Clinical observations suggest the existence of subpopulations of TNS responders and non-responders [17]. However, electrical stimulation of the nervous system is a clinically established method of relieving the pain due to damage or disease of the somatosensory pathways [10-12], but the electrical parameters, by which nerve fibres are excited or inhibited, are not well defined [13,14,18]. No clear rules exist on optimal frequency ranges to be used in the treatment of various disorders. Different frequencies of TNS have been reported to have varying effects [2,7,16]. In the study of Ashton et al. [2] TNS frequency of 8 Hz appeared to raise the ice-pain threshold, and 100 Hz was ineffective. In the recent study by Johnson et al. [7] TNS frequencies ranging from 20 Hz to 80 Hz produced the greatest analgesia in cold-induced pain, while frequencies below and above this level produced effects of lesser magnitude. Their study also suggested that frequency

of pulse delivery was the governing factor. Sj61und [16] studied a range of peripheral nerve stimulating frequencies in the rat and reported that 80 Hz produced the maximal suppression of the C-fibre evoked flexion response. Eriksson et al. [6] used short bursts of pulse trains with an interval frequency of 100 Hz and a repetition rate of 1-4 Hz and suggested that this method was effective in some pain conditions. Connelty et al. [5] studied repetitive stimuli of pulse trains and found that train-of-four produced significantly less discomfort than double-burst stimulation. TNS frequencies of 40-100 Hz are widely used in the clinical environment. Most commercial stimulators have only one mode of stimulation, namely conventional continuous stimulation at a constant frequency (commonly 30-100 Hz). Some transcutaneous stimulators have in addition a burst mode, in which highfrequency (100 Hz) trains of pulses are repeated at a burst frequency of 2 Hz. The test stimulator employed in this trial, in addition to conventional constant stimulation, had 2 frequency-modulated signals: high-rate frequency modulation (HRFM) and low-rate frequency modulation (LRFM), plus burst mode of stimulation. The rationale for including frequency modulation is the physiological fact that receptor (and nerve) adaptation occurs, leading to reduced response or therapeutic effect. Frequency modulation of the stimulus obviates, at least in part, this phenomenon and delivers what are essentially novel stimuli to which the nervous system responds without adaptation [15]. Part I of our pilot study [19] demonstrated that patients treated with transcutaneous stimulation preferred frequency-modulated and burst stimulation rather than conventional constant mode. This trial was performed to validate the long-term results of the pilot study. Fourteen pain conditions out of 21 (66%) responded well to the stimulation, the majority preferring HRFM and burst-type stimulation. Sj61und et al. [6] reported that lumbago responded best to continuous stimulation and sciatica to acupuncture-like (burst) stimulation. In this trial, burst mode of stimulation appeared to be most effective for sciatica, and the patients suffering from low-back pain responded best to HRFM stimulation. These results validate the initial testing of different stimulation modes before assessing long-term stimulation therapy. Since the basis of pain is the perception of changes in the patterns of nerve impulses [4,9,20], it may be worthwhile to modify the pattern of stimulation pulses instead of keeping them constant, as in the conventional continuous mode of stimulation. This could be a rational approach to improve the results of TNS treatment. This also implies that it is time for an improvement in the design and production of TNS equipment.

t62

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17 Thompson, J.W., The role of transcutaneous electrical nerve stimulation (TENS) l~r the control of pare. hi: D. Doyle {Ed.), 1986 International Symposium on Pain Control. Roy. Soc. Med. Services, London, 1987. pp. 27 47. 18 Tulgar. M., Basic parameters for safe and effective clcctrical stimulation of the nervous systems, Postgraduate Pain Management Course, Pain Relief Foundation. l,iverpool, November. 1989. 19 Tulgar, M., McGhme, F., Bowsher. D. and Miles, J.B,, ('omparatire effectiveness of different stimulation modes in relieving pain. Part 1. A pilot study, Pain Relief Foundation. Walton llospital, Liverpool, 1990. 20 Wall, P.D., Mechanisms of acute and chronic pain, Adv. Pare Res. Ther., fl (1984) 95-- 102. 21 Wolf, S.L., Gersh, M.R. and Rao, V.R., Examination of electrode placements and stimulating paramcters in treating chronic pain with conventional transcutaneous electrical nerve stimulation (-FENS), Pain, 11 (19811 37 47.