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Pain, 4 7 ( 1 9 9 1 ) 1 5 1 - 1 5 5 1 5 1 1 9 9 1 E l s e v i e r S c ie n c e P u b l i s h e r s B . V . A l l r i g h t s r e s e w e d 0 3 0 4 - 3 9 5 9 / 9 1 / $ 0 3 . 5 0

P A I N 0 18 59

C o m p a r a t i v e e f f e c t iv e n e s s o f d i f fe r e n t s ti m u l a t i o n m o d e si n r e l i e v i n g p a i n . P a r t I . A p i l o t s t u d y

Metin Tu lgar a, Francis Mc Glo ne ~, David Bowsher " and Jo hn B. Miles bPain Research Institute, Pain Relief Foundation, Walton Hospital, Liuerpool L9 IA E (U.K.), and b Departmen t o f Neurological Science, Unit,ersity

of Lit 'erpool, Walton Hospital, Licerpool L9 1AE (U.K.)( R e c e iv e d 1 No v e m b e r 1 9 9 0 , r e v i s io n re c e iv e d 1 1 Fe b r u a r y 1 9 9 1 , a c c e p t e d 1 M a r c h 1 9 91 )

Summary In this pilot study, to assess the optimal stimulation parameters, 3 different forms of transcutaneouselectrical nerve stimulation were performed in 27 patients.Conventional continuous stimulation with a constant frequency of 70 Hz, burst stimulation (90 msec trains ofpulses with an internal frequency of 100 Hz repeated at 2 Hz, each train consisting of 10 pulses), and frequency-modulated stimulation (continuous pulses changed from 90 Hz to 55 Hz over 90 msec) were randomly delivered tothe patients for half an hour in 3 separate sessions. The patients were blind to the modes of stimulation.

This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modula-tion and burst rather than conventional constant mode.Key words: Transcu taneous electrical nerve stimulation; Stimulation modes; Stimulation parameters

Introduct ionElectrical stimulation has been used as a clinical

tool to relieve pain for many centur ies [3,13-16]. Al-though the application is old, unfortunately the opti-mal parameters to be used are still not clear [18,19,23].Various types of signal, such as rectangular pulses,sinusoidal pulses, constant and modula ted pulses, trainsof pulses, have been applied by many researchers indifferent species, e.g., rats, cats, dogs, rabbits, monkeysand man [2,5,8,t0,11,17,20,22,24,25]. It is difficult tocome to any clear conclusion regarding parameters ofstimulation and pain relief obtained from the pub-lished work. Confusion in this field sometimes leads tomisuse of this otherwise clinically useful treatment.Studies on ice-pain by Ashton et al. [1] and Johnson etal. [9] suggest some correlation between the frequencyand pain relief. Eriksson et al. [7] and Connelly et al.

[4] also reported differential effects of short bursts ofpulse trains.In this study, the ability of transcutaneously deliv-ered stimulus patterns (conventional, burst and fre-

quency modulated) to relieve pain was investigated. Apurpose-built stimulator made at the Pain ResearchInstitute, Liverpool University, was employed. Firstly, apilot study was done in which 27 patients participated,and we report the results of this study. The second partof the study will be a long-term follow-up of thetreatment.

The patients were given 2 different stimulationmodes: conventional constant stimulation, burst stimu-lation and frequency-modulated stimulation in 3 sepa-rate sessions. This pilot study demonstrated that pa-tients preferred frequency-modulated and burst stimu-lation rather than conventional constant mode.

MethodsCorrespondence to: M e t i n T u l g a r , P h . D . R e s e a r c h e r , P a i n R e l i e fFo u n d a t io n , W a l to n Ho sp i t a l , R i c e L a n e , L iv e r p o o l L 9 1 AE , U . K .

The electrical parameters of commercially availablestimulators are limited. For this reason, a new test

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15 2T A B L E 1D A T A O F T H E P A T I E N T S P A R T I C I P A T I N G I N T I l E P I L O TS T U D YL B P = l o w b a c k p ai n ; P O P ~ p o s t o p e r a t i v e p a i n : M D S = r n a s t ic a t o r yd y s fu n c ti o n s yn d r o m e ; P h L = p h a n t o m l i m b p a i n : C T I l = c h r o n i ct e n s i o n h e a d a c h e .P a t i e n t c h a r a c t e r is t i c s N u m b e rA g e ( y e a r s ) 2 6 - 7 3 ( m e a n : 4 2 . 5)S ex

M e n 1 6W o m e n 1 1

D i a g n o s i sLBP 9P O P 5S h o u l d e r p a i n 4S c i a l i c a 3M D S 3P h L p a i n I( ' a u s a l g i a 1C T t t 1T o t a l 2 7

P r e v i o u s t r e a t m e n tC o n v e n t i o n a l T N S 5D r u g s 1 5

s t i m u l a t o r w a s c o n s t r u c t e d t o t e s t t h e t h e r a p e u t i c e f -f e c t i v e n e s s o f d i f f e r e n t s i g n a l s u s e d i n e l e c t r i c a l s t i m u -l a t i o n o f t h e n e r v o u s s y s t e m s f o r t h e r e l i e f o f p a i n . I t i sb a s i c a l l y a t r a n s c u t a n e o u s n e r v e s t i m u l a t o r w i t h f r e -q u e n c y - m o d u l a t e d s t i m u l a t i o n i n a d d i t i o n t o c o n v e n -t i o n a l c o n s t a n t a n d b u r s t m o d e s . T h e r e a r e s e le c t o rs w i t c h e s t o s e l e c t t h e s t im u l a t i o n m o d e s a n d f r e q u e n -c i e s f or e a c h m o d e . T h e r e i s a l s o a s e p a r a t e p u l s e - w i d t hs e l e c to r s w i t c h w h i c h p r o v i d e s a s e l e c t i o n o f p u l s e sr a n g i n g f r o m 5 0 / x s e c t h r o u g h 2 0 0 / x s e c , 3 5 0 tx s e c a n d5 0 0 / x se c . R o t a r y s e l e c t o r s w i t c h e s w e r e u s e d i n s t e a do f p o t e n t i o m e t e r s i n o r d e r t o e n s u r e c o r r e c t s e l e c t i o no f t h e p a r a m e t e r s .

P a r t i c ip a t i n g i n t h is s t u d y w e r e t w e n t y - s e v e n p a -t ie n t s: 1 8 f r o m W a l t o n H o s p i t a l a n d 9 fr o m t h e P a i nC l i n i c o f t h e M e d i c a l F a c u l t y o f t h e U n i v e r s i t y o fI s t a n b u l . D a t a a b o u t t h e s e p a t i e n t s i s g i v e n i n T a b l e I .

T r e a t m e n t o f e a c h p a t i e n t w a s p e r f o r m e d i n 3 s e s -s i o n s : ( 1 ) c o n v e n t i o n a l c o n s t a n t s t i m u l a t i o n , ( 2 ) b u r s ts t i m u l a t i o n a n d ( 3 ) f r e q u e n c y - m o d u l a t e d s t i m u l a t i o n .I n c o n s t a n t m o d e , c o n t i n u o u s p u l s e s w i t h 70 H z f r e -q u e n c y w e r e d e l i v e r e d . D u r i n g b u r st m o d e , t h e c o n -s t a n t f r e q u e n c y s e l e c t o r s w i t c h w a s s e t f o r 1 0 0 H z a n dt h e b u r s t f r e q u e n c y s e l e c t o r s w i t c h f o r 2 H z , t h u s t r a i n so f 1 0 0 H z w e r e d e l i v e r e d t w i c e a s e c o n d , e a c h t r ai nc o n s i s t i n g o f 1 0 p u l s e s o v e r 9 0 m s e c . I n f r e q u e n c ym o d u l a t i o n , t h e c o n s t a n t - f r e q u e n c y s e l e c t o r s w i tc h w a ss e t fo r 7 0 H z a n d f r e q u e n c y - m o d u l a t i o n s e l e c t o r s w i t c hf o r 1 H z , s o t h a t c o n t i n u o u s p u l s e s c o u l d b e c h a n g e df r o m 9 0 H z t o 5 5 H z o v e r 9 0 m s e c . A s y m m e t r i c b i p h a -

100 v/dw 200 us/d]v

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. . . . ~ - q C H ~

F i g . 1 . A s i n g l e p u l s e a p p l i e d i n a l l s t i m u l a t i o n m o d e s .

5,00 v/dry 2 0 0 ms/d l vr r 1 - - - - ~ r - r . . . . . . ~ - i - - l

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Fig. 2 . O u t p u t o f t h e s t i m u l a t o r w h e n s e t f o r t h e c o n v e n t i o n a lc o n s t a n t m o d e o f s t i m u l a t i o n .

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Fig. 3 , O u t p u t o f t h e s t i m u l a t o r w h e n s e t f o r t h e b u r s t m o d e o fs t i m u l a t i o n .

s i c r e c t a n g u l a r p u l s e s w i t h a d u r a t i o n o f 2 0 0 t x s e c w e r ee m p l o y e d i n a l l m o d e s . P l o t t e d o u t p u t s o f t h e s t im u l a -t o r f o r e a c h m o d e a r e s h o w n i n F i g s. 1 - 4 .

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_ L L _ L L L M L L L L C H I

F i g. 4 . O u t p u t o f t h e s t i m u l a t o r w h e n s e t f or t h e f r e q u e n c y - m o d -u l a t e d s t i m u l a ti o n .

Th e e lec t rod es were p laced f or op t imal d i s t r ib u t ionof paraesthes ia and opt imal pain rel ief in al l cases .Burst s t imulat ion is somet imes cal led acupuncture- l ikest imulat ion [7 ] , but mu scle twitch was no t necessari lyobtained in the present s tudy.

15 3

T h e o r d e r i n w h i c h s t i m u l a t i o n m o d e s w e r e d e l i v -e r e d w a s r a n d o m . T h e p a t i e n t s w e r e b l i n d e d t o t h em o d e s o f s ti m u l a ti o n . D i f f e r e n t s t i m u l a t i o n m o d e s w e r eu s e d o n d i f f e r e n t d a y s. E a c h s e s s i o n l a s te d h a l f a nh o u r .

T h e i n t e n s it y o f t h e s t i m u l a t i o n u s e d w a s h a l f - w a yb e t w e e n t h e s t i m u l a t i o n p e r c e p t i o n t h r e s h o l d a n d t h et o l e r a n c e l e v e l f o r e a c h p a t i e n t [ 1 3 ] .V i s u a l a n a l o g u e s c a l e s ( V A S ) w e r e u s e d t o a s s e s st h e p a i n s c o r e s im m e d i a t e l y b e f o r e b e g i n n i n g t r e a t -m e n t a n d w i t h in 1 0 m i n a f t e r s t o p p i n g s t i m u l a t i o n . T h er e s u l t s o b t a i n e d w e r e r e c o r d e d i n a c h a r t f o r e a c hp a t i e n t .

ResultsResults obtained from this p i lot s tudy are shown in

Tables II and III . Table II shows the s t imulat ion modesthat appeared to be most ef fect ive for each pat ient . I tincludes their age, sex, d iagnosis and pain scores . Asseen from this table , 16 out of 27 pat ients reported thatf req u en cy- mod u lat ed s t imu lat ion was more b en ef ic ia l

T A B L E IIE F F E C T I V E S T I M U L A T I O N M O D E S F O R E A C H C A S EC = c o n v e n t i o n a l c o n s t a n t s t i m u l a t i o n ; B = b u r s t s t i m u l a t i o n ; F M = f r e q u e n c y - m o d u l a t e d s t i m u l a ti o n .P a t i e n t S e x A g e D i a g n o s i s E f f e c t i v e( N ) s t i m u l a t i o n

m o d eV A S m a g n i t u d e o f p a inB e f o r e A f t e r

1 M 3 5 L B P F M 6 0 1 52 M 2 7 S h o u l d e r p a i n B 5 0 3 53 M 3 6 L B P F M 4 0 2 54 M 4 8 P O P B / F M 9 0 0 / 05 M 4 9 S c ia t ic a B / F M 6 0 0 / 06 F 4 0 L B P B / F M 8 0 6 0 / 6 07 M 5 1 S h o u l d e r p a i n B / F M 9 0 7 0 / 7 08 M 3 9 P O P B / F M 9 0 7 0 / 7 09 F 3 9 L B P - 8 0 8 0

1 0 M 3 3 S c i a t i c a B 6 0 2 01 1 M 7 0 L B P F M 7 0 4 01 2 M 3 7 P O P B 8 9 6 01 3 M 2 7 P O P F M 8 7 5 01 4 F 2 8 L B P F M 5 0 2 715 M 5 2 P O P C / B / F M 3 5 0 / 0 / 01 6 M 3 7 P h L B 7 5 3 51 7 F 5 4 L B P F M 4 5 3 01 8 M 5 5 C a u s a lg i a - 6 4 6 41 9 F 2 6 S h o u l d e r p a i n F M 9 0 5 22 0 F 4 0 M D S B 7 5 4 52 1 F 2 9 M D S F M 6 7 1 52 2 F 3 5 C T H F M 1 8 02 3 F 5 3 L B P B 5 0 2 02 4 F 3 3 M D S B 2 2 1 12 5 M 4 2 L B P B 2 5 02 6 F 6 0 S h o u l d e r p a i n C / B / F M 6 0 2 0 / 2 0 / 2 02 7 M 7 3 S c i at i ca C / B / F M 5 0 2 0 / 2 0 / 2 0

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154TA BL E 111DISTRIBUTION OF EFFECTIVE STIMULATION MODES AC-CORDING TO DIAGNOSISl)iagnosis Pa t ie n t s S t im ulat io n odes (N)

(N) C B FMLBP 9 3 5POP 5 1 4 4Shoulder pain 4 l 3 3Nciatica 3 I 3 2MDS 3 - 2 1PhL pain 1 I('ausalgia 1 --( T t t I 1Tota l 27 3 I (~ I ~

f o r t h e i r t y p e o f p a i n . S i x t e e n p a t i e n t s f o u n d b u r s tm o d e m o r e e f f e c t i v e . O n l y 3 o u t o f 2 7 p a t i e n t s d e -s c r i b e d c o n v e n t i o n a l c o n s t a n t s t i m u l a t i o n t o b e a s e f -f e c t i v e a s t h e o t h e r m o d e s ; 2 p a t i e n t s d i d n o t r e s p o n dt o a n y m o d e o f s t i m u l a t i o n .

T a b l e I I I sh o w s t h e d i s t r ib u t i o n o f th e n u m b e r o fs t i m u l a t i o n m o d e s a c c o r d i n g t o d i a g n o s i s. S i x o f t h ep a t i e n t s w i t h l o w - b a c k p a i n ( L B P ) f o u n d f r e q u e n c y -m o d u l a t e d s t i m u l a t i o n m o s t e f f e c t i v e , w h i ls t 2 o f th e s ep a t i e n t s f o u n d b u r s t m o d e t o b e m o r e b e n e f i c i a l . M o s to f t h e p a t i e n t s w i t h s h o u l d e r p a i n , p o s t o p e r a t i v e p a i n( P O P ) a n d s c i a t i c a r e p o r t e d t h a t b o t h b u r s t a n d f r e -q u e n c y m o d u l a t i o n h a d t h e s a m e e f f e c t . T w o o u t o f th e3 p a t i e n t s w i t h m a s t i c a t o r y d y s f u n c t i o n s y n d r o m e( M D S ) p r e f e r r e d b u r s t m o d e , w h i l e t h e o t h e r p a t i e n tf o u n d f r e q u e n c y m o d u l a t i o n t o b e m o r e b e n e f i c i a l .O n e p a t i e n t w i t h c h r o n i c t e n s i o n h e a d a c h e ( C T H )r e p o r t e d t h a t f r e q u e n c y - m o d u l a t e d s t im u l a t io n d i m i n-i s h e d h e r p a i n m o r e e f f e c t i v e l y .

D i s c u s s i o n

T w e n t y - s e v e n p a t i e n t s ( 9 w i t h L B P , 5 w i t h P O P , 4w i t h s h o u l d e r p a i n , 3 w i t h s c i a t i c a , 3 w i t h M D S , 1 w i t hP h L p a i n , 1 w i t h c a u s a l g i a a n d 1 w i t h c h r o n i c t e n s i o nh e a d a c h e ( C T H ) ) p a r t i c i p a t e d i n t h i s s t u d y . F i v e o ft h e s e p a t i e n t s h a d p r e v i o u s l y b e e n t r e a t e d w i t h c o n -v e n t i o n a l t r a n s c u t a n e o u s n e r v e s t i m u l a t i o n ( T N S ) a n dm o s t o f t h e m h a d u s e d d r u g s . A ll b u t 2 p a t i e n t s d e -r i v e d s o m e b e n e f i t f r o m t h e t r e a t m e n t , a t l e a s t o nin i t i a l t e s t i n g .T h e a n a l g e s i c e f f e c t s o f c o n t i n u o u s m o d e o f T N Sh a v e b e e n s t u d i e d o n c o l d - i n d u c e d p a i n [ 1 , 9 ] . A s h t o ne t a l . [ 1 ] r e p o r t e d t h a t T N S a t 8 H z r a i s e d i c e - p a i nt h r e s h o l d , b u t o n l y 2 f r e q u e n c i e s w e r e s t u d i e d ( 8 H za n d 1 0 0 H z ) . J o h n s o n e t a l . [ 9 ] e x t e n d e d t h e s e e a r l i e rf i n d in g s b y e x a m i n i n g t h e e f f e c t s o f 5 d i f f e r e n t s t i m u l a -t i o n f r e q u e n c i e s ( 1 0 , 2 0 , 4 0 , 8 0 a n d 1 6 0 H z ) a n d r e -

p o r t e d t h a t T N S f r e q u e n c i es o f 2 0 - 8 0 t t z p r o d u c e dt h e g r e a t e s t a n a l g e s i a . T h e y a l s o r e p o r t e d t h a t n os i g n i f i c a n t d i f f e r e n c e s i n s t i m u l u s i n t e n s i t y w c r c o b -s e r v e d , s u g g e s t i n g t h a t f r e q u e n c y o f p u l s e d c l i v c r y w a st h e g o v e r n i n g f a c t o r . S j 6 h m d [ 21 ] f o u n d t h a t o v e r ar a n g e o f p e r i p h e r a l n e r v e s t i m u l a t i n g f r e q u e n c i c s , 8 0H z p r o d u c e d t h e m a x i m a l s u p p r e s s i o n o [ t h c ( M ' i b r ce w ) k e d f l e x i o n r e s p o n s e i n t h e r a t . E r i k s s o n e t a l . [ 7 ]t e s t e d s h o r t b u r s t s o f p u l s e t r a i n s w i t h a n i n t e r n a lf r e q u e n c y o f 1 0 0 H z a n d a r e p e t i t i o n r a t e o f 1 - 4 H za n d s u g g e s t e d t h a t t h i s m e t h o d w a s e f f c c t i v c i n s o m ep a i n c o n d i t i o n s . C o n n e l l y e t a l . [ 4 ] r e p o r t c d t h a t r e p e t i -t i ve s t i m u l i o f a t r a i n o f 4 p r o d u c e d s i g n i f ic a n t l y l e s sd i s c o m f o r t t h a n d o u b l e - b u r s t s t i m u l a t i o n .

I n a r e c c n t s t u d y , E k s t r o m a n d S j 6 1u n d [ () ] s t i m u -l a t e d t h e p l a n t a r a n d s u r a l n e r v e s i n o n e l i m b o f th er a t a n d r e c o r d e d f l e x i o n r e f l e x a n d n c r v c v o l l e y s f r o ms c i a t i c n e r v e i n t h e s a m e l i m b , e m p l o y i n g v a r i a t i o n sa r o u n d a c e n t r e f r e q u e n c y o f 85 H z o f I f) a n d 2 0 e a c hi n 2, 6 o r 15 s e c p e r i o d s . T h e y r e p o r t e d t h a t , i n t h e i rs t u d y , m o d u l a t i o n o f f r e q u e n c y d i d n o t r e s u l t i n as i g n i f i c a n t i n c r e a s e i n t h e e f f i c a c y o f s t i m u l a t i o n . T h e r ea r e m a n y o t h e r w a y s t o m o d u l a t e t h e f r e q u e n c y a n d a l lp o s s i b i l i t i e s m u s t b e a s s e s s e d b e f o r e a n y f i r m c o n c l u -s i o n s c a n b e d r a w n . T h i s p i l o t s t u d y h a s d e m o n s t r a t e dt h a t p a t i e n t s t r e a t e d w i t h T N S p r e f e r m o d u l a t e d s t i m -u l a t i o n m o d e s s u c h a s f r e q u e n c y m o d u l a t i o n a n d b u r s tr a t h e r t h a n c o n v e n t i o n a l c o n t i n u o u s s t i m u l a t i o n . T h ep r e f e r e n c e a p p e a r e d t o b e a c o m b i n a t i o n o f t h e p l e a s -a n t n a t u r e o f t h e t r e a t m e n t a n d t h e a n a l g e s i c e ff e c t .

T h e m a j o r i t y o f p a t i e n t s w i th L B P p r e f e r r e d f r e -q u e n c y - m o d u l a t e d s t i m u l a t i o n f o r t r e a t m e n t . P a t i e n t sw i t h P O P , s c i a t i c a a n d s h o u l d e r p a i n r e p o r t e d t h a tb o t h b u r s t a n d f r e q u e n c y m o d u l a t i o n h a d t h e s a m ee f f e c t . T h e s e r e s u l t s s u g g e s t t h a t f r e q u e n c y - m o d u l a t e ds t i m u l a t i o n c o u l d b e m o r e e f f e c t i v e f o r p a t i e n t s s u f f e r -i n g L B P . B u r s t a n d f r e q u e n c y m o d u l a t i o n s e e m t o h a v ct h e s a m e e f f e c t i n r e l i e v i n g P O P a n d s h o u l d e r p a i n .

S o m e p a t i e n t s w i t h a p p a r e n t l y t h e s a m e t y p e o f p a i ns y n d r o m e r e s p o n d e d t o d i f f e r e n t f o r m s o f s t i m u l a t io n .I t w o u l d , t h e r e f o r e , s e e m t o b e c l in i c a l ly i m p o r t a n t t oo f f e r e a c h p a t i e n t a t r i a l o f a r a n g e o f s t i m u l a t i o nm o d e s b e f o r e a t t e m p t i n g a n y l o n g - t e r m t r i a l .

S i n c e b u r s t a n d f r e q u e n c y - m o d u l a t e d s t i m u l a t i o na p p e a r t o be p r e f e r r e d b y p a t i e n t s , t h e d e s i g n o f a n e ws t i m u l a t o r in w h i c h b o t h o f t h e s e m o d e s c a n b e a p p l i e ds e e m e d i n d i c a t e d . T h e t e s t s t i m u l a t o r w a s , t h e r e f o r e ,m o d i f i e d f o r l o n g - t e r m t r i a l o f i t s e f f i c i e n c y , a n d ad o u b l e - b l i n d c o n t r o l l e d T N S s t u d y w a s p l a n n e d t oc o m p a r e t h e l o n g - t e r m e f f e c t s o f d i f f e r e n t s t i m u l a t i o nm o d e s .

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