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The effects of non-painful transcutaneous electrical nerve stimulation on cutaneous pain threshold and muscular reflexes in normal men and in subjects with chronic pain
Pain, 11 (1981) 49--63
49
Elsevier/North-Holland Biomedical Press
THE EFFECTS OF NON-PAINFUL TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION ON CUTANEOUS PAIN THRESHOLD AND MUSCULAR REFLEXES IN NORMAL MEN AND IN SUBJECTS WITH CHRONIC PAIN
FABIO FRANCINI 1o*,MARCO MARESCA 2, PAOLO PROCACCI 2 and MASSIMO ZOPPI 2 I Cattedra di Fisiologia Generale, 2 Cattedra di Terapia Medica Sistematica, Servizio di Algologia, University o f Florence, 1-50134 Florence (Italy) (Received 23 May 1980, accepted 11 March 1981)
SUMMARY In healthy subjects and in subjects with chronic r~_yofascial pain of one lower limb, the following was measured in both lower limbs: (i) sequential Hoffman (H) reflex, (ii) sequential Achilles tendon (T) reflex, (iii) cutaneous pain threshold determined with electrical stimuli, before, during and after transcutaneous electrical nerve stimulation (TENS). In healthy subjects no significant differences were observed between the pain thresholds of the two limbs. During and after TENS, changes of the reflexes were related to the pain thresholds. In the pathological subjects a significant difference of pain threshold was present between the affected limb and the contralateral one. An important difference between healthy and pathological subjects is not the quality but the quantity of the changes induced by TENS, in the sense that the levels of inhibition and facilitation of the reflexes are more evident in patients with pain. Indeed, TENS induces a reset of sensory and of motor system and a parallel long lasting effect both on sensory and on muscular function, with concomitant pain relief in the pathological subjects.
INTRODUCTION In normal subjects the cutaneous pain threshold of a limb does not significantly differ from that of the opposite limb, using thermal [7] and electrical stimuli [ 12]. * Correspondence to be sent to: Prof. Fabio Francini, Istituto di Fisiologia Umana, Universit~ di Firenze, Viale Morgagni 63, 1-50134 Florence, Italy.
0304-3959/81/0000--0000/$02.50 © 1981 Elsevier/No~ Holland Biomedical Press
50 Subjects suffering from chronic myofascial pain of one lower limb differ from normal subjects in that the sensory thresholds in the affected side are higher or lower than in the opposite side (lateralization) [19,22,23]. Certain patterns of sensory stimulation in intact, freely moving mammals cause desynchronization of the EEG associated with the arousal reaction. Other patterns of sensory stimulation produce behavioral and/or EEG manifestations of sleep. In the cat it was observed that low rate electrical stimulation of the group II cutaneous afferents may produce behavioral sleep, synchronization of the EEG, decre~e of the postural tone of the neck, extensor and flexor muscles and reduction of the heteronymous monosynaptic and polysynaptic reflexes. On the other hand, high rate electrical stimulation of group II cutaneous afferents, above 12--16 Hz, and low or high rate stimulation of group III cutaneous afferents produces behavioral arousal, EEG desynchronization, increase of the muscular tone and facilitation of the heteronymous monosynaptic and polysynaptic reflexes [ 18]. Transcutaneous electrical nerve stimulation (TENS) has been used in man for relief of pain. The pain relief obtained by TENS is often long lasting [1,9,17,20,21]. TENS induces an increase of cutaneous pain threshold in the distribution area of the stimulated nerve [i0,11,14,20,21,23,24] as well as threshold changes outside this area [10,11,14,23]. Outside this area the thresholds become higher where they had been low prior to TENS and conversely, where prior to TENS they were high, they become lower. In other words, TENS reduces the differences among the various subjects [ 10,11,23]. In a previous paper we reported that non-painful TENS in normal humans inhibits the Hoffmann (H) reflex in the stimulated limb. The Hoffmann reflex is elicited by electrical stimulation of the popliteal nerve and can be recorded as an electromyographic response in the soleus muscle. Two components of the response are identified: the first component, M response, is due to the direct stimulation of the motoneurons, the second component, H response, is a reflex monosynaptic response, due to the stimulation of the afferent fibers from spindle endings (group IA) [ 21]. In the present research we studied the changes induced by TENS on the H reflex, on the Achilles tendon reflex (T) and on the cutaneous pain threshold in normal subjects and in subjects suffering from chronic myofascial pain of one lower limb. The experimental conditions for T and H reflexes vary from one subject to another and from one experiment to another or from one limb to the contralateral limb, using the same subject, due to small differences of placement of stimulating and recording electrodes or differences in the position of the hammer [ 15]. To eliminate these variables, we examined the percent change of the reflexes induced by TENS. In order to observe whether changes of H reflex (AH) induced by TENS differed from changes of T reflex {AT), we compared AH and AT-AH.
51 MATERIALS AND METHODS
Subjects The investigation was carried out on 40 healthy :~.ubjects, 25 males and 15 females, aged 23--47, and on 25 patients of our pain clinic (Servizio di Algologia), 20 males and 5 females, aged 24--56, suffering from chronic myofascial pain in one lower limb with a typical "trigger p o i n t " at the junction between m. triceps surae and the Achilles tendon. Fully informed c o n s e n t to participate in this study was obtained from all subjects. During the experiments the subjects were seated in a comfortable chair built for this purpose. Noise in the environment was avoided.
TENS Transcutaneous electrical nerve stimulation (TENS) was carried out with non-polarizable rectangular electrodes 3 cm × 7 cm. The cathode was placed on the posterior surface of the leg over the n. cutaneus surae medialis at the junction between m. triceps surae and the Achilles t e n d o n and the anode on the anterior surface of the leg. The pulses were c o n s t a n t current rectangular waves of 1 msec at a frequency of 50 Hz. These parameters of stimulation were used because t h e y induced a well-tolerated tingling sensation [20,21]. The subjects felt sharp non-painful tingling in the posterior surface of the leg distal to the electrode. During TENS the intensity of the current was varied to maintain a constant tingling sensation.
Pain threshold The cutaneous pain threshold was measured after a period of instruction and training. Electrical stimuli were given to the skin of the anterior ,;urface of the thighs by means of non-polarizable surface electrodes 8 mm diameter. Stimuli were 20 msec trains of 1 msec square waves at a frequency of 250 Hz. Each train was repeated every second. The pain threshold expressed in mA was evaluated by the method of limits [12,16], i.e., the stimulus strength was successively increased with notation of the value when the subject perceived pricking pain, then the stimulus was successively decreased with notation of the value when pain disappeared. This procedt~re was repeated at least 3 times. The mean of all readings was used to den,',~te the threshold.
Tendon (T) reflex To elici'L the T reflex, the Achilles tendon was tapped with an electromechanic hammer at a constant strength that induced a good response in the m. soleus where the recording surface electrodes were placed. The angle, the distance from the t e n d o n and the site of tapping of the hm~nmer were exactly controlled. The head, the limbs and the angle between the foot ~n_d the ~::~ikle of the subjects were fixed.
52
Hoffmann (H) reflex H reflex was elicited stimulating the popliteal nerve and recording the response from the m. soleus with non-polarizable surface electrodes.
Procedure First group of subjects.
The effects of TENS on recruitment curves of the H reflex were studied in 7 healthy subjects. TENS was given during 40 min. E v e n 5 min we obtained a recruitment curce of the H reflex alternating between the limb where TENS was applied and the contralateral limb; thus each limb was examined every 10 min. Each point of the H (reflex) and M (direct) curve is the average of 6 peak-to-peak values obtained by increasing the intensity of the current from threshold for the H response and 6 peak-to-peak values obtained by decreasing the intensity of the current at the point of the maximum of the M curve w i t h o u t an H response. The tests were carried o u t for 20 min before TENS, during TENS, and for 35 min after TENS. Second group of subjects. In 33 healthy subjects and in the whole group of patients the effects of TENS on sequential T and H reflexes and on cutaneous pain threshold were studied. From the recruitment curves obtained in the first group of subjects (see Results) we observed that TENS induced ch~mges in the H response w i t h o u t variations of the direct m o t o r (M) response. This finding permitted us to study the effects of TENS on sequential H reflexes. For the H response, the intensity of the stimulus on the popliteal nerve was adjusted before TENS in order to obtain from the m. soleus an H response that was 50% of the maximal H response [15]. Each experimental session was shorter than in the first group of subjects to minimize discomfort. Every subject was examined for 10 min before TENS, during TENS which was given during 24 min, and for 25 min after TENS. During the whole experimental session T and H reflexes were induced every 4 sec. The cutaneous pain threshold (PaTh) was tested 3 times before TENS, at the 4th and at the 22nd min of TENS and at the 4th and 20th min after TENS. The general procedure of the experiments for each subject was the following: 1st session of TENS: T contralateral to rlENS, PaTh ipsi- and contralateral; 2nd session of TENS: T ipsilateral to TENS, PaTh ipsi- and contralateral; 3rd session of TENS: H contr~lateral to TENS, PaTh ipsi- and contralateral; 4th session of TENS: H ipsilateral to TENS, PaTh ipsi- and contralateral. Between each session the interval was 3 days. For the analysis of the results we considered a reliable value for the H and T reflexes the average of at least 30 sequential reflexes. RESULTS
As we have observed in a previous study [10,23], repeated changes of the current were necessm-y to maintain a constant degree of tingling within the
53 !00
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150% Mrna~ Fig. 1. R e c r u i t m e n t curves of the H o f f m a n n reflex in one h e a l t h y subject. The ordinate shows a m p l i t u d e of the M (direct) and H (reflex) response, expressed as a ~.ercentage of the maximal M response. T h e abscissa shows c u r r e n t intensity expressed in relative values, where 1 is the c u r r e n t intensity p r o d u c i n g an M response which was 50% of the maximal M response. T h e curves m a r k e d with filled dots were obtained before TENS (B). The curves m a r k e d with o p e n squares were o b t a i n e d starting at the 4 0 t h ( I P S I L A T E R A L ) and at the 45th ( C O N T R A L A T E R A L ) rain o f TENS. Each d o t or square is the mean of 6 values obtained by progressively increasing the intensity of t h e stimulus and 6 values o b t a i n e d by progressively decreasing the intensity of the stimulus.
first 10 min of TENS. This was named "unsteady state" (changing phase) of TENS. During the subsequent period of stimulation, few or no changes of intensity were necessary. This was named "steady state" of TENS. The intensity of the current at which the subjects first perceived a sharp non-painful tingling was 0.4--0.6 mA. During the steady state the intensity of the current was 2--11 mA. Influence o f T E N S on the H reflex recruitment curve During TENS we observed in 7 healthy subjects a decrease of the maxiE)
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54
mum of the H curve in the stimulated limb and an increase in the contralateral limb. In both limbs the M curve showed no change (Fig. 1). In both iimbs 30 min after the completion of TENS the H curve returned to preTENS level {Fig. 2).
Time course of TE~S-induced changes of H and T reflexes and pain thresholds Healthy subjects. The subjects were divided into 3 groups on the basis of the mean value of their pain threshold (PaTh) before TENS: (i) subjects with PaTh less than 2.5 mA (low PaTh); (ii) subjects with PaTh between 2.5 IPSILATERAL
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Fig. 3. T and H reflexes: (A) heaith~ subject with low pain threshold before TENS; (B) healthy subje=t with high pain threshold before TENS. Ordinate: per cent variations from the mean values before TENS. Abscissa: time. The thick line is the period of TENS. Each step represents the average of 30 sequential reflexes.
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AT--AH AH APaTh
Steady state of TENS
After TENS
- - 1 9 . 0 ± 2.5 * --7.3±2.1" + 4 0 . 1 ± 3.1 ***
- - 2 2 . 5 ± 3.3 ** --9.5 _+ 0.2 * + 2 8 . 2 ± 2.0 ***
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- - 1 5 . 2 ± 2.5 * --5.1± 1.9NS +32.1 ± 2.7 ***
- - 2 1 . 0 + 3.2 ** +0.3 _+ 0.3 NS + 3 2 . 3 _+ 2.2 ***
+ 2 7 . 2 _+ 2.9 ** 0 ± 0.04 NS - - 1 4 . 3 ± 4 NS
+ 1 7 . 1 + 1.6 *** 0 ±0.02NS - - 1 7 . 2 + 2.2 ***
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+ 3 6 . 2 _+ 2.1 *** +2.5_+ 0.7 NS - - 3 1 . 2 _+ 3 ***
AT=T--T° To
H--H o × 100;APaTh PaTh--PaTh o × 1 0 0 ; A H = - Ho = PaTho × 100.
Mean _+ S.E.; NS = n o t s i g n i f i c a n t ; * = P < 0 . 0 5 ; ** = P < 0 . 0 1 ; *** = P < 0 . 0 0 1 ;
AT--AH AH APaTh
Unsteady state of TENS
+7.1 +_ 1.6 * 0 _+0.02NS - - 1 4 . 3 ± 2.3 **
- - 7 . 5 _+ 2.4 NS +5.0 + 1.1 * - - 1 7 . 5 _+ 2.6 **
+ 3 5 . 3 + 2.0 *** +2.4 _+ 0.7 NS - - 3 2 . 3 _+ 3 ***
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Ipsi
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M i d d l e P a T h (12 s u b j e c t s )
L o w P a T h (7 s u b j e c t s )
+ 2 1 . 2 _+ 1.4 *** +1.5_+0.5NS - - 4 6 . 3 ± 4 . 2 ***
- - 1 7 . 1 + 2.2 ** - - 1 6 . 2 _+ 2.3 ** - - 4 3 . 5 _+ 3.2 ***
+43.1 _+ 2.2 *** +9.1 + 1.1 ** - - 5 6 . 4 _+ 3.5 ***
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+9.2 ._" 1.4 ** +3.5 _+ 0.5 ** - - 4 1 . 3 _+ 4.5 **
--5.1 _+ 2.0 N$ +7.5 + 1.2 ** - - 3 9 . 4 _+ 3.3 ***
+ 4 4 . 2 _+ 2.3 *** +9.0 _+ 1.1 ** - - 5 7 . 3 + 3.6 ***
Contra
High P a T h (14 s u b j e c t s )
A T : per c e n t v a r i a t i o n s o f t h e t e n d o n r e f l e x (T) f r o m t h e m e a n values b e f o r e T E N S (To). A H : per c e n t v a r i a t i o n s o f t h e H r e s p o n s e ( H ) f r o m t h e m e a n values b e f o r e T E N S (H0). A P a T h : per c e n t v a r i a t i o n s o f t h e c u t a n e o u s p a i n t h r e s h o l d f r o m the m e a n v a l u e s b e f o r e T E N S ( P a T h 0 ) (average o f t w o e x p e r i m e n t a l sessions). L o w P a T h , m i d d l e P a T h , h i g h P a T h : s u b j e c t s w i t h low, m i d d l e a n d h i g h c u t a n e o u s p a i n t h r e s h o l d s b e f o r e T E N S . To a n d H0: m e a n values o f T a n d H r e f l e x e s b e f o r e T E N S . A T a n d A H are c a l c u l a t e d for e a c h s u b j e c t : d u r i n g t h e u n s t e a d y state o f T E N S , o n t h e m e a n o f 30 s e q u e n t i a l r e f l e x e s ( 5 t h a n d 6 t h m i n ) ; d u r i n g t h e s t e a d y state, o n t h e m e a n o f 3 0 0 s e q u e n t i a l r e f l e x e s (last 10 m i n o f T E N S ) ; a f t e r T E N S o n t h e m e a n o f 3 0 0 s e q u e n t i a l r e f l e x e s (first 10 m i n a f t e r T E N S ) .
C H A N G E S O F T R E F L E X , H R E F L E X A N D P A I N T H R E S H O L D D U R I N G A N D A F T E R T E N S IN H E A L T H Y S U B J E C T S
TABLE I
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56 and 3.5 mA (middle PaTh); (iii) subjects with PaTh more than 3.5 mA (high PaTh). Before TENS the H response magnitude as expressed in per cent of the direct M response was 10 + 5,2% higher in subjects with low pain threshold them in subjects with high pain threshold. This difference is not statistically significant. During the unsteady state of TENS, in comparison to the values before TENS we observed: (i) a significant increase of AT.AH in both legs that is more marked (P < 0.001) in the subjects with high pain thresholds; in these subjects there is also a significant bilateral increase of AH but of a lower degree (Table I; Fig. 3); (ii) a bilateral decrease of the pain thresholds that is significant in the group with middle and high pain thresholds (Table I). When plotting the reflex changes against the pain threshold changes of all the sube~IPSI
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Fig. 4. Relations between changes of the pain threshold and of the reflex responses in every healthy subject. Ordinate: triangles, per cent variations of the H response of sequential Hoffmann reflexes from the mean values before TENS (AH); dots, per cent variations of the tendon reflex minus the H response of sequential Hoffmann reflexes from the mean values before TENS (AT-AH). Abscissa: per cent variations of the cutaneous pain threshold (APaTh) from the mean values before TENS. Filled symbols, leg where TENS was applied (IPSI). Open symbols, leg contralateral to TENS (CONTRA). A: unsteady state of TENS. AH and AT were calculated on the mean values of the reflexes obtained during the 5th and 6th min of TENS (30 sequential reflexes). B: steady state of TENS. AH and AT were calculated on the mean values of the reflexes of the last 10 rain of TENS (300 sequential reflexes). C: after TENS. AH and AT were calculated on the mean values of the reflexes for 10 rain after TENS (300 sequential reflexes).
jects during this period, they exhibit an inverse relationship (linear regression test, paired samples: AT-AH of the stimulated limb: r =--0.66, P < 0.001; AT.AH of the contralateral limb: r = --0.66, P < 0.001; 5 H of the stimulated limb: r = --0.70, P < 0.001; AH of the contralateral limb: r = - - 0 . 6 9 , P < 0.001) (Fig. 4A). During the steady state of TENS, in compariso., to the values before TENS we observed: (i) a bilateral decrease of AT-AH, more marked in the subjects with low pain thresholds; a AH decrease and a concomitant conlralateral increase more marked (P < 0.05} in the high threshold subjects {Fig. 3, Table I); (ii) significant bilateral changes of pain threshold which increases in the subjects with low thresholds and decreases in the subjects with high thresholds (Table I). As during the unsteady state of TENS there seems to be an inverse relationship between the changes of pain threshold and: (i) 5TA H of the stimulated limb (r = --0.68, P < 0.001); (ii)A T - A H of the contralateral limb (r = --0.84, P < 0.001); (iii) A H of the contralateral limb (r = --0.66, P < 0.001). However, there is a direct relationship between the changes of pain threshold and All of the stimulated limb (r = 0.78, P < 0.001) (Fig. 4B). After TENS, in comparison to the values before T E N S we noticed a signfficant decrease of A H of the stimulated limb e~d of A T - A H of both limbs
T A B L E II
--35±4"** --15+ 1.5"* +34+4"**
AT-AH AH APaTh
After TENS
+2"* +0.2" _+ 3NS
--4.26+8NS
_+12NS
_+ 1 5 " * *
± 10 **
AT = T - - T o To
+30± 1.2" +5+0.7" --44+5"**
--6 _+ 0.5 NS --4 + 0.8 NS --40+3"**
+86+4"** +18 + 1.5 ** --48+5"*
+16+1.1NS +12 + 0 . 6 . * +2-+2NS
--5 _+ 0.5 NS +8 + I . I * +3+2NS
+82+5"** +14 + 2 ** --14_+4NS
-- PaTh o × 100; A(I---C) = PaTh(ipSi}PaTh(ipsi)--PaTl~(c°ntra--) × 100; AH = H - - H o x 100; PaTh = PaThPaTho Ho
Mean _+ S.E.; NS = n o t significant; * = P < 0.05; ** = P < 0.01; *** = P < 0.001;
--15 --5 --1
--20
--20 _+ 2.2 ** --5 + 0.5 * +40±3"**
AT-AH AH APaTh
Steady state of T E N S
--16 _+ 2.8 ** +0.I + 0.4 NS +18 + 2 " *
--80
+4.5"* _+ 0.04 NS +4"
+18+4.2" 0 + 0.05 NS --31+5"**
AT-AH AH &PaTh
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--44
PaTh
Before TENS Unsteady state of T E N S
Contra
Ipsi
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Ipsi
Contra
PaTh: Ipsi > Contra (10 subjects)
PaTh: Ipsi < Contra (15 subjects)
+ 9 **
--13.3 + 7 NS
--10.8 + 6 NS
--4.1 + 4 NS
+34
A(I-C)
AT: per cent variations of the tendon reflex (T) from the mean values before TENS (To}. AH: per cent variations of the H response (H) from the mean values before TENS (H0). APaTh: variations of the cutaneous pain threshold from the mean vaiues before TENS (PaTh0) (average of two experimental sessions). A(I-C): per cent differences between the sensory thresholds of the painful limb (lpsi) versus the ccntralateral one (Contra). Ipsi < Contra: patients with lower pain threshold before TENS in the affected limb. Ipsi > Contra: subjects with higher pain threshold before T E N S in the affected limb. AT and AH are calculated for each subject: during the unsteady state of TENS, on the mean of 30 sequential reflexes (5th and 6th rain); during the steady state, on the mean of 300 sequential reflexes (last 10 min of TENS); after TENS on the mean of 300 sequential reflexes (first 10 min after TENS).
C H A N G E S OF T R E F L E X , H R E F L E X AND PAIN T H R E S H O L D D U R I N G AND A F T E R TENS IN THE SUBJECTS WJTH PAIN
C.,n
59 in the subjects with low thresholds and a significant increase of AH of the contralateral limb and of AT-AH of both limbs in the subjects with high thresholds. The average of the reflex responses obtained during the first 10 rain after TENS did not significantly differ from the average of the responses obtained in the following 10 min (Fig. 3, Table I). No significant changes of pain threshold were observed in comparison to the steady state both at the 4th and at the 20th min after TENS (Table I). There is an inverse relationship between the changes of reflexes and the changes of pain threshold (Z~TAH of the stimulated limb: r = - - 0 . 9 4 , P < 0.001; AT-AH of the contralateral limb: r = - - 0 . 9 2 , P < 0.001; AH of the stimulated limb: r = - - 0 . 9 6 , P < 0.001; AH of the contralateral limb: r = --0.95, P < 0.001) (Fig. 4C). Subjects with pare. The pain threshold before TENS in the limb where the patients had chronic pain was significantly different from that in the opposite limb (P < 0.001). Therefore the patients were divided in two groups: subjects with pain thresholds in the affected limb lower or higher than in the opposite limb (Table II). Before TFNS the H reflex magnitude as expressed in per cent of the direct M response was 16 + 15% higher in the limb with low pain threshold than in the contralateral limb. This difference is not statistically significant. During the unsteady state of TENS, in comparison to the values before TENS we observed: in the patients with lower thresholds in the painful limb, a significant bilateral increase of AT-AH, more marked in the opposite limb; in the patients with higher thresholds in the painful limb, a significant bilaterM increase of AT-AH and of AH, more marked than in the previous group (AT-AH: P < 0.001; AH: P < 0.01) (Fig. 5, Table II). The pain thresholds decreased in all patients more in the paintul limb than in the contralateral limb. As a consequence, the difference between the two limbs increased in the patient,s with lower thresholds in the painful limb and d.creased in the other group (Table II). During the steady state of TENS, in comparison to the values before TENS we observed: in both groups a bilateral decrease of AT-AH and a decrease of AH in the painful limb; in the group with lower thresholds in the painful limb, a significant increase of thresholds in both limbs, which was more marked in the painful limb (P < 0.001); in the group with higher thresholds in the painful limb, a decrease of thresholds in the painful limb and no significant change in the contralateral limb. We can observe that in both groups the difference of pain thresholds between the limbs was less than before TENS (Fig. 5, Table II). After TENS, in comparison to the values before TENS, in the group with lower thresholds in the painful limb we observed a decrease of AT-AH and of AH, more marked in the painful limb (P < 0.001). In the other group we observed an increase of AT-AH and of AH, more marked in the painful limb (P < 0.001). The average of the reflexes obtained during the first 10 min after TENS did not significantly differ from the average of the reflexes obtained in the following 10 min {Fig. 5, Table II). Pain thresholds at the 4th and at the 20th min after TENS did not significantly change in comparison with the steady state of TENS {Table II).
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Fig. 5. T and H reflexes. A: patient with lower pain threshold before TENS in the painful limb than in the contralateral limb. B: patient with higher pain threshold before TENS in the painful limb than in the contralateral limb. Ordinate: per cent variations from the mean values before TENS. Abscissa: time. The thick line is the period of TENS. Each step represents the average of 30 sequential reflexes.
DISCUSSION
The most important result of this investigation is that the magnitudes of the TENS-induced changes in the pain thresholds and in the H and T reflexes are correlated.
61 The changes of the Hoffmann reflex during TENS are due to central mechanisms acting on ~-motoneurons, as the M curve did not change. We could therefore use the changes of sequential H responses as indices of the changes of the central control of the ~-motoneurons in the second group of subjects. During the unsteady state of TENS, the increase of the amplitude of the reflex responses and the lowering of the pain threshold outside the distribution area of the stimulated nerve is probably due to a general facilitation of ~he afferent and efferent somatic paths. During the steady state of TENS, in the subjects with high pain threshold before TENS, the pain threshold decreases; in the subjects with low pain *hreshold, the pain threshold increases. Thi~ can be interpreted as a resetting of the pain threshold. AT-AH decreases in both limbs, AH decreases in the stimulated limb of all subjects. This may be due to an inhibitory action of TENS on motor reflexes. The contralateral facilitation of H reflex may be due to the crossed innervation. After the end of TENS, the resetting of the pain threshold persists for at ieast 20 min. The reflexes are inhibited in the subjects with low pain threshold before TENS: facilitated in the subjects with high pain ~hreshold. This pattern can be considered as a resetting of the motor function concomitant with the resetting of the sensory function. The changes of AT-AH are always greater than the changes of AH. This difference may be due to an action on the interneuronal level; consequently, the effects on 7-motoneurons are more marked than on a-motoneurons. In fact, the path from primary afferents to 3'-motoneurons contains interneutons whereas that to a-motoneurons does not [ 3--5]. Another possibility is a presynaptic inhibition [2,8] more evident on the tendon reflex that is less synchronized than the H reflex [13]. The relationship between the changes of the reflexes and the changes of the thresholds is of an inverse nature: as the amplitude of reflexes increases, as the pain threshold decreases. The only exception is the direct relationship between the changes of H reflex and the changes of pain threshold during the steady state of TENS in the stimulated limb: as the amplitude of the reflex increases, as the pain threshold increases. This may be due to the reciprocal innervation as the cutaneous afferents stimulated by TENS may induce changes of the reflex activity of flexor muscles. In general, our experiments put in evidence a relationship between sensory thresholds and reflex responses. When the pain threshold before TENS is low, TENS induces an inhibition both on the afferent and on the efferent side; when the pain threshold before TENS is high, the main effect is a facilitation on both sides. These parallel effects on the afferent and efferent sides may be explained by a control of interneurons exerted by TENS. An important difference between normal and pathological subjects is that both facilitation and inhibition of the sensorimotor system during and after TENS are more marked in subjects with pain than in normal subjects. Another difference between normal and pathological subjects is that in
62
subjects with pain the pain threshold in the painful limb is not the same as in the other limb. This lateralization is reduced by TENS. This finding is in agreement with the results of Callaghan et al. [6]. In conclusion ' TENS induces a reset of sensory and of motor systems and a parallel long lasting effect both on sensory and on muscular functions with concomitant pain relief in the pathological subjects. REFERENCES 1 Andersson, S.A. and Holmgren, E., Pain threshold effects of peripheral conditioning stimulation. In: J.J. Bonica and D.G. Albe-Fessard (Eds.), Advances in Pain Research and Therapy, Voi. 1, Raven Press, New York, 1976, pp. 761--768. 2 Barnes, C.O. and Pompeiano, O., Presynaptic and postsynaptic effects in the monosynaptic reflex pathway to extensor motoneurons following vibration of synergic muscles, Arch. ital. Biol., 108 (1970) 259--294. 3 Bathien, N., Rdflexes spinaux chez l'homme et niveaux d'attention, Electroenceph. clin. Neurophysiol., 30 (1971) 32--37. 4 Bathien, N. et Hugelin~ A., R~flexes monosynaptiques et polysynaptiques de l'homme au cours de l'attention, Electroenceph. clin. Neurophysiol., 26 (1969) 605--612. 5 Brunia, C.H.M., Effect of propranolol on monosynaptic reflex activity during task, Appl. Neurophysiol., 42 (1979) 135--144. 6 Callaghan, M., Sternbach, R.A., Nyquist, J.K. and Timrnermans, G., Changes in somatic ,sensitivity during transcutaneous electrical analgesia, Pain, 5 (1978) 115-127. 7 Della Corte, M., Procacci, P., Bozza, G. and Buzzelli, G., A study on the cutaneous pricking pain threshold in normal man, Arch. Fisiol., 64 (1965) 141--170. 8 Delwaide, P.J., Human monosynaptic reflexes and presynaptic inhibition. In: J.E. Desmedt (Ed.), New Developments in Electromyography and Clinical Neurophysiology, Vol. 3, Karger, Basel, 1973, pp. 508--522. 9 Eriksson, M.B.E. and Sjblund, B.H., Acupuncture-like electroanalgesia in TNSresistant chronic pain. In: Y. Zotterman (Ed.), Sensory Functions of the Skin, Pergamon Press, Oxford, 1976, pp. 575--581. 10 Francini, F. and Maresca, M., Local and generalized changes of the cutaneous sensory thresholds during transcutaneous electrical stimulation (TES) in healthy subjects and in patients with chronic pain. In: Pain Abstracts, Vol. I, International Association for the Study of Pain, Seattle, Wash., 1978, p. 127. 11 Francini, F., Procacci, P., Zoppi, M. and Maresca, M., Mechanisms of action of transcutaneous ele~'trical stimulation (TES) for relief of pain (electroanalgesia), Neurosci. Lett., Suppl. ~ (1978) 431. 12 Francini, F., Z~ppi, M., Maresca, M. and Procacci, P., Skin potential and EMG changes induced by cutaneous electrical stimulation. I. Normal man in arousing and non-arousing, environment, Appl. Neurophysiol., 42 (1979) 113--124. 13 Gassel, M.M. and Diarnantopoulos, E., Nerve potential recordings during electrically and mechanically evoked monosynaptic reflexes in man, Nature (Lond.), 208 (1965) 1004--1005. 14 Hiedl, P., Struppler, A. and Gessler, M.. TNS-evoked long loop effects, Appl. Neurophysiol., 42 (1979) 153--159. 15 Hugon, M., Methodology of the Hoffmann reflex in man. In: J.E. Desmedt (Ed.), New Developments in Flectromyography and Clinical Neurophysiology, Vol. 3, Karger, Basel, 1973, pp. 277--293. 16 Lindblom, U. and Meyerson, B.A., Influence on touch, vibration and cutaneous pain of dorsal column stimulation in man, Pain, 1 (1975) 257--270.
63 17 Long, D.M. and Hagfors, N., Electrical stimulation in the nervous system: the current status of electrical stimulation of the nervous system for relief of pain, Pain, 1 (1975) 109--123. 18 Pompeiano, O., Reticular formation. In: A. Iggo (Ed.), Handbook of Sensory Physiology, Somatosensory System, Vol. II, Springer, Berlin, 1973, pp. 393--415. 19 Procacci, P., Francini, F., Zoppi, M. and Maresca, M., Cutaneous pain threshold changes after sympathetic block in reflex dystrophies, Pain, 1 (1975) 167--175. 20 Procacci, P., Zoppi, M. e Maresca, M., La terapia delle sindromi dolorose con stimolazione elettrica (elettroanalgesia), Clin. Ter., 73 (1975) 465--474. 21 Procacci, P., Zoppi, M., Maresca, M. and Francini, F., Hypoalgesia induced by transcutaneous electrical stimulation. A physiological and clinical investigation, J. neurosurg. Sci., 21 (1977) 221--228. 22 Procacci, P., Francini, F., Maresca, M. and Zoppi, M., Skin potential and EMG changes induced by cutaneous e|~etrlcg! stimulation. II. Subjects with reflex sympathetic dystrophies, Appl. Neuropbysiol., 42 (1979) 125--134. 23 Procacci, P., Zoppi, M., Francini, F , Maresca, M. e Bernardini, U.D., Variazioni locali e generalizzate delle soglie sensitive cutanee durante stimolazione elettrica transcutanea in soggetti normali e in pazienti con dolore cronico. In: C.A. Pagni, P. Procacci and V. Ventafridda (Eds.), II l~olore, Problemi di Fisiopatologia e Terapia, Edizioni Cortina, Verona, 1979, pp. 135--146. 24 Taub, A. and Campbell, J.N., Percutaneous local electrical analgesia: peripheral mechanisms. In: J.J. Bonica (Ed.), Advances in Neurology, Vol. 4, Raven Press, New York, 1974, pp. 733--736.
49
Elsevier/North-Holland Biomedical Press
THE EFFECTS OF NON-PAINFUL TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION ON CUTANEOUS PAIN THRESHOLD AND MUSCULAR REFLEXES IN NORMAL MEN AND IN SUBJECTS WITH CHRONIC PAIN
FABIO FRANCINI 1o*,MARCO MARESCA 2, PAOLO PROCACCI 2 and MASSIMO ZOPPI 2 I Cattedra di Fisiologia Generale, 2 Cattedra di Terapia Medica Sistematica, Servizio di Algologia, University o f Florence, 1-50134 Florence (Italy) (Received 23 May 1980, accepted 11 March 1981)
SUMMARY In healthy subjects and in subjects with chronic r~_yofascial pain of one lower limb, the following was measured in both lower limbs: (i) sequential Hoffman (H) reflex, (ii) sequential Achilles tendon (T) reflex, (iii) cutaneous pain threshold determined with electrical stimuli, before, during and after transcutaneous electrical nerve stimulation (TENS). In healthy subjects no significant differences were observed between the pain thresholds of the two limbs. During and after TENS, changes of the reflexes were related to the pain thresholds. In the pathological subjects a significant difference of pain threshold was present between the affected limb and the contralateral one. An important difference between healthy and pathological subjects is not the quality but the quantity of the changes induced by TENS, in the sense that the levels of inhibition and facilitation of the reflexes are more evident in patients with pain. Indeed, TENS induces a reset of sensory and of motor system and a parallel long lasting effect both on sensory and on muscular function, with concomitant pain relief in the pathological subjects.
INTRODUCTION In normal subjects the cutaneous pain threshold of a limb does not significantly differ from that of the opposite limb, using thermal [7] and electrical stimuli [ 12]. * Correspondence to be sent to: Prof. Fabio Francini, Istituto di Fisiologia Umana, Universit~ di Firenze, Viale Morgagni 63, 1-50134 Florence, Italy.
0304-3959/81/0000--0000/$02.50 © 1981 Elsevier/No~ Holland Biomedical Press
50 Subjects suffering from chronic myofascial pain of one lower limb differ from normal subjects in that the sensory thresholds in the affected side are higher or lower than in the opposite side (lateralization) [19,22,23]. Certain patterns of sensory stimulation in intact, freely moving mammals cause desynchronization of the EEG associated with the arousal reaction. Other patterns of sensory stimulation produce behavioral and/or EEG manifestations of sleep. In the cat it was observed that low rate electrical stimulation of the group II cutaneous afferents may produce behavioral sleep, synchronization of the EEG, decre~e of the postural tone of the neck, extensor and flexor muscles and reduction of the heteronymous monosynaptic and polysynaptic reflexes. On the other hand, high rate electrical stimulation of group II cutaneous afferents, above 12--16 Hz, and low or high rate stimulation of group III cutaneous afferents produces behavioral arousal, EEG desynchronization, increase of the muscular tone and facilitation of the heteronymous monosynaptic and polysynaptic reflexes [ 18]. Transcutaneous electrical nerve stimulation (TENS) has been used in man for relief of pain. The pain relief obtained by TENS is often long lasting [1,9,17,20,21]. TENS induces an increase of cutaneous pain threshold in the distribution area of the stimulated nerve [i0,11,14,20,21,23,24] as well as threshold changes outside this area [10,11,14,23]. Outside this area the thresholds become higher where they had been low prior to TENS and conversely, where prior to TENS they were high, they become lower. In other words, TENS reduces the differences among the various subjects [ 10,11,23]. In a previous paper we reported that non-painful TENS in normal humans inhibits the Hoffmann (H) reflex in the stimulated limb. The Hoffmann reflex is elicited by electrical stimulation of the popliteal nerve and can be recorded as an electromyographic response in the soleus muscle. Two components of the response are identified: the first component, M response, is due to the direct stimulation of the motoneurons, the second component, H response, is a reflex monosynaptic response, due to the stimulation of the afferent fibers from spindle endings (group IA) [ 21]. In the present research we studied the changes induced by TENS on the H reflex, on the Achilles tendon reflex (T) and on the cutaneous pain threshold in normal subjects and in subjects suffering from chronic myofascial pain of one lower limb. The experimental conditions for T and H reflexes vary from one subject to another and from one experiment to another or from one limb to the contralateral limb, using the same subject, due to small differences of placement of stimulating and recording electrodes or differences in the position of the hammer [ 15]. To eliminate these variables, we examined the percent change of the reflexes induced by TENS. In order to observe whether changes of H reflex (AH) induced by TENS differed from changes of T reflex {AT), we compared AH and AT-AH.
51 MATERIALS AND METHODS
Subjects The investigation was carried out on 40 healthy :~.ubjects, 25 males and 15 females, aged 23--47, and on 25 patients of our pain clinic (Servizio di Algologia), 20 males and 5 females, aged 24--56, suffering from chronic myofascial pain in one lower limb with a typical "trigger p o i n t " at the junction between m. triceps surae and the Achilles tendon. Fully informed c o n s e n t to participate in this study was obtained from all subjects. During the experiments the subjects were seated in a comfortable chair built for this purpose. Noise in the environment was avoided.
TENS Transcutaneous electrical nerve stimulation (TENS) was carried out with non-polarizable rectangular electrodes 3 cm × 7 cm. The cathode was placed on the posterior surface of the leg over the n. cutaneus surae medialis at the junction between m. triceps surae and the Achilles t e n d o n and the anode on the anterior surface of the leg. The pulses were c o n s t a n t current rectangular waves of 1 msec at a frequency of 50 Hz. These parameters of stimulation were used because t h e y induced a well-tolerated tingling sensation [20,21]. The subjects felt sharp non-painful tingling in the posterior surface of the leg distal to the electrode. During TENS the intensity of the current was varied to maintain a constant tingling sensation.
Pain threshold The cutaneous pain threshold was measured after a period of instruction and training. Electrical stimuli were given to the skin of the anterior ,;urface of the thighs by means of non-polarizable surface electrodes 8 mm diameter. Stimuli were 20 msec trains of 1 msec square waves at a frequency of 250 Hz. Each train was repeated every second. The pain threshold expressed in mA was evaluated by the method of limits [12,16], i.e., the stimulus strength was successively increased with notation of the value when the subject perceived pricking pain, then the stimulus was successively decreased with notation of the value when pain disappeared. This procedt~re was repeated at least 3 times. The mean of all readings was used to den,',~te the threshold.
Tendon (T) reflex To elici'L the T reflex, the Achilles tendon was tapped with an electromechanic hammer at a constant strength that induced a good response in the m. soleus where the recording surface electrodes were placed. The angle, the distance from the t e n d o n and the site of tapping of the hm~nmer were exactly controlled. The head, the limbs and the angle between the foot ~n_d the ~::~ikle of the subjects were fixed.
52
Hoffmann (H) reflex H reflex was elicited stimulating the popliteal nerve and recording the response from the m. soleus with non-polarizable surface electrodes.
Procedure First group of subjects.
The effects of TENS on recruitment curves of the H reflex were studied in 7 healthy subjects. TENS was given during 40 min. E v e n 5 min we obtained a recruitment curce of the H reflex alternating between the limb where TENS was applied and the contralateral limb; thus each limb was examined every 10 min. Each point of the H (reflex) and M (direct) curve is the average of 6 peak-to-peak values obtained by increasing the intensity of the current from threshold for the H response and 6 peak-to-peak values obtained by decreasing the intensity of the current at the point of the maximum of the M curve w i t h o u t an H response. The tests were carried o u t for 20 min before TENS, during TENS, and for 35 min after TENS. Second group of subjects. In 33 healthy subjects and in the whole group of patients the effects of TENS on sequential T and H reflexes and on cutaneous pain threshold were studied. From the recruitment curves obtained in the first group of subjects (see Results) we observed that TENS induced ch~mges in the H response w i t h o u t variations of the direct m o t o r (M) response. This finding permitted us to study the effects of TENS on sequential H reflexes. For the H response, the intensity of the stimulus on the popliteal nerve was adjusted before TENS in order to obtain from the m. soleus an H response that was 50% of the maximal H response [15]. Each experimental session was shorter than in the first group of subjects to minimize discomfort. Every subject was examined for 10 min before TENS, during TENS which was given during 24 min, and for 25 min after TENS. During the whole experimental session T and H reflexes were induced every 4 sec. The cutaneous pain threshold (PaTh) was tested 3 times before TENS, at the 4th and at the 22nd min of TENS and at the 4th and 20th min after TENS. The general procedure of the experiments for each subject was the following: 1st session of TENS: T contralateral to rlENS, PaTh ipsi- and contralateral; 2nd session of TENS: T ipsilateral to TENS, PaTh ipsi- and contralateral; 3rd session of TENS: H contr~lateral to TENS, PaTh ipsi- and contralateral; 4th session of TENS: H ipsilateral to TENS, PaTh ipsi- and contralateral. Between each session the interval was 3 days. For the analysis of the results we considered a reliable value for the H and T reflexes the average of at least 30 sequential reflexes. RESULTS
As we have observed in a previous study [10,23], repeated changes of the current were necessm-y to maintain a constant degree of tingling within the
53 !00
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150% Mrna~ Fig. 1. R e c r u i t m e n t curves of the H o f f m a n n reflex in one h e a l t h y subject. The ordinate shows a m p l i t u d e of the M (direct) and H (reflex) response, expressed as a ~.ercentage of the maximal M response. T h e abscissa shows c u r r e n t intensity expressed in relative values, where 1 is the c u r r e n t intensity p r o d u c i n g an M response which was 50% of the maximal M response. T h e curves m a r k e d with filled dots were obtained before TENS (B). The curves m a r k e d with o p e n squares were o b t a i n e d starting at the 4 0 t h ( I P S I L A T E R A L ) and at the 45th ( C O N T R A L A T E R A L ) rain o f TENS. Each d o t or square is the mean of 6 values obtained by progressively increasing the intensity of t h e stimulus and 6 values o b t a i n e d by progressively decreasing the intensity of the stimulus.
first 10 min of TENS. This was named "unsteady state" (changing phase) of TENS. During the subsequent period of stimulation, few or no changes of intensity were necessary. This was named "steady state" of TENS. The intensity of the current at which the subjects first perceived a sharp non-painful tingling was 0.4--0.6 mA. During the steady state the intensity of the current was 2--11 mA. Influence o f T E N S on the H reflex recruitment curve During TENS we observed in 7 healthy subjects a decrease of the maxiE)
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54
mum of the H curve in the stimulated limb and an increase in the contralateral limb. In both limbs the M curve showed no change (Fig. 1). In both iimbs 30 min after the completion of TENS the H curve returned to preTENS level {Fig. 2).
Time course of TE~S-induced changes of H and T reflexes and pain thresholds Healthy subjects. The subjects were divided into 3 groups on the basis of the mean value of their pain threshold (PaTh) before TENS: (i) subjects with PaTh less than 2.5 mA (low PaTh); (ii) subjects with PaTh between 2.5 IPSILATERAL
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A T : per c e n t v a r i a t i o n s o f t h e t e n d o n r e f l e x (T) f r o m t h e m e a n values b e f o r e T E N S (To). A H : per c e n t v a r i a t i o n s o f t h e H r e s p o n s e ( H ) f r o m t h e m e a n values b e f o r e T E N S (H0). A P a T h : per c e n t v a r i a t i o n s o f t h e c u t a n e o u s p a i n t h r e s h o l d f r o m the m e a n v a l u e s b e f o r e T E N S ( P a T h 0 ) (average o f t w o e x p e r i m e n t a l sessions). L o w P a T h , m i d d l e P a T h , h i g h P a T h : s u b j e c t s w i t h low, m i d d l e a n d h i g h c u t a n e o u s p a i n t h r e s h o l d s b e f o r e T E N S . To a n d H0: m e a n values o f T a n d H r e f l e x e s b e f o r e T E N S . A T a n d A H are c a l c u l a t e d for e a c h s u b j e c t : d u r i n g t h e u n s t e a d y state o f T E N S , o n t h e m e a n o f 30 s e q u e n t i a l r e f l e x e s ( 5 t h a n d 6 t h m i n ) ; d u r i n g t h e s t e a d y state, o n t h e m e a n o f 3 0 0 s e q u e n t i a l r e f l e x e s (last 10 m i n o f T E N S ) ; a f t e r T E N S o n t h e m e a n o f 3 0 0 s e q u e n t i a l r e f l e x e s (first 10 m i n a f t e r T E N S ) .
C H A N G E S O F T R E F L E X , H R E F L E X A N D P A I N T H R E S H O L D D U R I N G A N D A F T E R T E N S IN H E A L T H Y S U B J E C T S
TABLE I
¢J1
56 and 3.5 mA (middle PaTh); (iii) subjects with PaTh more than 3.5 mA (high PaTh). Before TENS the H response magnitude as expressed in per cent of the direct M response was 10 + 5,2% higher in subjects with low pain threshold them in subjects with high pain threshold. This difference is not statistically significant. During the unsteady state of TENS, in comparison to the values before TENS we observed: (i) a significant increase of AT.AH in both legs that is more marked (P < 0.001) in the subjects with high pain thresholds; in these subjects there is also a significant bilateral increase of AH but of a lower degree (Table I; Fig. 3); (ii) a bilateral decrease of the pain thresholds that is significant in the group with middle and high pain thresholds (Table I). When plotting the reflex changes against the pain threshold changes of all the sube~IPSI
e~
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Fig. 4. Relations between changes of the pain threshold and of the reflex responses in every healthy subject. Ordinate: triangles, per cent variations of the H response of sequential Hoffmann reflexes from the mean values before TENS (AH); dots, per cent variations of the tendon reflex minus the H response of sequential Hoffmann reflexes from the mean values before TENS (AT-AH). Abscissa: per cent variations of the cutaneous pain threshold (APaTh) from the mean values before TENS. Filled symbols, leg where TENS was applied (IPSI). Open symbols, leg contralateral to TENS (CONTRA). A: unsteady state of TENS. AH and AT were calculated on the mean values of the reflexes obtained during the 5th and 6th min of TENS (30 sequential reflexes). B: steady state of TENS. AH and AT were calculated on the mean values of the reflexes of the last 10 rain of TENS (300 sequential reflexes). C: after TENS. AH and AT were calculated on the mean values of the reflexes for 10 rain after TENS (300 sequential reflexes).
jects during this period, they exhibit an inverse relationship (linear regression test, paired samples: AT-AH of the stimulated limb: r =--0.66, P < 0.001; AT.AH of the contralateral limb: r = --0.66, P < 0.001; 5 H of the stimulated limb: r = --0.70, P < 0.001; AH of the contralateral limb: r = - - 0 . 6 9 , P < 0.001) (Fig. 4A). During the steady state of TENS, in compariso., to the values before TENS we observed: (i) a bilateral decrease of AT-AH, more marked in the subjects with low pain thresholds; a AH decrease and a concomitant conlralateral increase more marked (P < 0.05} in the high threshold subjects {Fig. 3, Table I); (ii) significant bilateral changes of pain threshold which increases in the subjects with low thresholds and decreases in the subjects with high thresholds (Table I). As during the unsteady state of TENS there seems to be an inverse relationship between the changes of pain threshold and: (i) 5TA H of the stimulated limb (r = --0.68, P < 0.001); (ii)A T - A H of the contralateral limb (r = --0.84, P < 0.001); (iii) A H of the contralateral limb (r = --0.66, P < 0.001). However, there is a direct relationship between the changes of pain threshold and All of the stimulated limb (r = 0.78, P < 0.001) (Fig. 4B). After TENS, in comparison to the values before T E N S we noticed a signfficant decrease of A H of the stimulated limb e~d of A T - A H of both limbs
T A B L E II
--35±4"** --15+ 1.5"* +34+4"**
AT-AH AH APaTh
After TENS
+2"* +0.2" _+ 3NS
--4.26+8NS
_+12NS
_+ 1 5 " * *
± 10 **
AT = T - - T o To
+30± 1.2" +5+0.7" --44+5"**
--6 _+ 0.5 NS --4 + 0.8 NS --40+3"**
+86+4"** +18 + 1.5 ** --48+5"*
+16+1.1NS +12 + 0 . 6 . * +2-+2NS
--5 _+ 0.5 NS +8 + I . I * +3+2NS
+82+5"** +14 + 2 ** --14_+4NS
-- PaTh o × 100; A(I---C) = PaTh(ipSi}PaTh(ipsi)--PaTl~(c°ntra--) × 100; AH = H - - H o x 100; PaTh = PaThPaTho Ho
Mean _+ S.E.; NS = n o t significant; * = P < 0.05; ** = P < 0.01; *** = P < 0.001;
--15 --5 --1
--20
--20 _+ 2.2 ** --5 + 0.5 * +40±3"**
AT-AH AH APaTh
Steady state of T E N S
--16 _+ 2.8 ** +0.I + 0.4 NS +18 + 2 " *
--80
+4.5"* _+ 0.04 NS +4"
+18+4.2" 0 + 0.05 NS --31+5"**
AT-AH AH &PaTh
+28 0 --16
--44
PaTh
Before TENS Unsteady state of T E N S
Contra
Ipsi
A(I-C)
Ipsi
Contra
PaTh: Ipsi > Contra (10 subjects)
PaTh: Ipsi < Contra (15 subjects)
+ 9 **
--13.3 + 7 NS
--10.8 + 6 NS
--4.1 + 4 NS
+34
A(I-C)
AT: per cent variations of the tendon reflex (T) from the mean values before TENS (To}. AH: per cent variations of the H response (H) from the mean values before TENS (H0). APaTh: variations of the cutaneous pain threshold from the mean vaiues before TENS (PaTh0) (average of two experimental sessions). A(I-C): per cent differences between the sensory thresholds of the painful limb (lpsi) versus the ccntralateral one (Contra). Ipsi < Contra: patients with lower pain threshold before TENS in the affected limb. Ipsi > Contra: subjects with higher pain threshold before T E N S in the affected limb. AT and AH are calculated for each subject: during the unsteady state of TENS, on the mean of 30 sequential reflexes (5th and 6th rain); during the steady state, on the mean of 300 sequential reflexes (last 10 min of TENS); after TENS on the mean of 300 sequential reflexes (first 10 min after TENS).
C H A N G E S OF T R E F L E X , H R E F L E X AND PAIN T H R E S H O L D D U R I N G AND A F T E R TENS IN THE SUBJECTS WJTH PAIN
C.,n
59 in the subjects with low thresholds and a significant increase of AH of the contralateral limb and of AT-AH of both limbs in the subjects with high thresholds. The average of the reflex responses obtained during the first 10 rain after TENS did not significantly differ from the average of the responses obtained in the following 10 min (Fig. 3, Table I). No significant changes of pain threshold were observed in comparison to the steady state both at the 4th and at the 20th min after TENS (Table I). There is an inverse relationship between the changes of reflexes and the changes of pain threshold (Z~TAH of the stimulated limb: r = - - 0 . 9 4 , P < 0.001; AT-AH of the contralateral limb: r = - - 0 . 9 2 , P < 0.001; AH of the stimulated limb: r = - - 0 . 9 6 , P < 0.001; AH of the contralateral limb: r = --0.95, P < 0.001) (Fig. 4C). Subjects with pare. The pain threshold before TENS in the limb where the patients had chronic pain was significantly different from that in the opposite limb (P < 0.001). Therefore the patients were divided in two groups: subjects with pain thresholds in the affected limb lower or higher than in the opposite limb (Table II). Before TFNS the H reflex magnitude as expressed in per cent of the direct M response was 16 + 15% higher in the limb with low pain threshold than in the contralateral limb. This difference is not statistically significant. During the unsteady state of TENS, in comparison to the values before TENS we observed: in the patients with lower thresholds in the painful limb, a significant bilateral increase of AT-AH, more marked in the opposite limb; in the patients with higher thresholds in the painful limb, a significant bilaterM increase of AT-AH and of AH, more marked than in the previous group (AT-AH: P < 0.001; AH: P < 0.01) (Fig. 5, Table II). The pain thresholds decreased in all patients more in the paintul limb than in the contralateral limb. As a consequence, the difference between the two limbs increased in the patient,s with lower thresholds in the painful limb and d.creased in the other group (Table II). During the steady state of TENS, in comparison to the values before TENS we observed: in both groups a bilateral decrease of AT-AH and a decrease of AH in the painful limb; in the group with lower thresholds in the painful limb, a significant increase of thresholds in both limbs, which was more marked in the painful limb (P < 0.001); in the group with higher thresholds in the painful limb, a decrease of thresholds in the painful limb and no significant change in the contralateral limb. We can observe that in both groups the difference of pain thresholds between the limbs was less than before TENS (Fig. 5, Table II). After TENS, in comparison to the values before TENS, in the group with lower thresholds in the painful limb we observed a decrease of AT-AH and of AH, more marked in the painful limb (P < 0.001). In the other group we observed an increase of AT-AH and of AH, more marked in the painful limb (P < 0.001). The average of the reflexes obtained during the first 10 min after TENS did not significantly differ from the average of the reflexes obtained in the following 10 min {Fig. 5, Table II). Pain thresholds at the 4th and at the 20th min after TENS did not significantly change in comparison with the steady state of TENS {Table II).
60
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Fig. 5. T and H reflexes. A: patient with lower pain threshold before TENS in the painful limb than in the contralateral limb. B: patient with higher pain threshold before TENS in the painful limb than in the contralateral limb. Ordinate: per cent variations from the mean values before TENS. Abscissa: time. The thick line is the period of TENS. Each step represents the average of 30 sequential reflexes.
DISCUSSION
The most important result of this investigation is that the magnitudes of the TENS-induced changes in the pain thresholds and in the H and T reflexes are correlated.
61 The changes of the Hoffmann reflex during TENS are due to central mechanisms acting on ~-motoneurons, as the M curve did not change. We could therefore use the changes of sequential H responses as indices of the changes of the central control of the ~-motoneurons in the second group of subjects. During the unsteady state of TENS, the increase of the amplitude of the reflex responses and the lowering of the pain threshold outside the distribution area of the stimulated nerve is probably due to a general facilitation of ~he afferent and efferent somatic paths. During the steady state of TENS, in the subjects with high pain threshold before TENS, the pain threshold decreases; in the subjects with low pain *hreshold, the pain threshold increases. Thi~ can be interpreted as a resetting of the pain threshold. AT-AH decreases in both limbs, AH decreases in the stimulated limb of all subjects. This may be due to an inhibitory action of TENS on motor reflexes. The contralateral facilitation of H reflex may be due to the crossed innervation. After the end of TENS, the resetting of the pain threshold persists for at ieast 20 min. The reflexes are inhibited in the subjects with low pain threshold before TENS: facilitated in the subjects with high pain ~hreshold. This pattern can be considered as a resetting of the motor function concomitant with the resetting of the sensory function. The changes of AT-AH are always greater than the changes of AH. This difference may be due to an action on the interneuronal level; consequently, the effects on 7-motoneurons are more marked than on a-motoneurons. In fact, the path from primary afferents to 3'-motoneurons contains interneutons whereas that to a-motoneurons does not [ 3--5]. Another possibility is a presynaptic inhibition [2,8] more evident on the tendon reflex that is less synchronized than the H reflex [13]. The relationship between the changes of the reflexes and the changes of the thresholds is of an inverse nature: as the amplitude of reflexes increases, as the pain threshold decreases. The only exception is the direct relationship between the changes of H reflex and the changes of pain threshold during the steady state of TENS in the stimulated limb: as the amplitude of the reflex increases, as the pain threshold increases. This may be due to the reciprocal innervation as the cutaneous afferents stimulated by TENS may induce changes of the reflex activity of flexor muscles. In general, our experiments put in evidence a relationship between sensory thresholds and reflex responses. When the pain threshold before TENS is low, TENS induces an inhibition both on the afferent and on the efferent side; when the pain threshold before TENS is high, the main effect is a facilitation on both sides. These parallel effects on the afferent and efferent sides may be explained by a control of interneurons exerted by TENS. An important difference between normal and pathological subjects is that both facilitation and inhibition of the sensorimotor system during and after TENS are more marked in subjects with pain than in normal subjects. Another difference between normal and pathological subjects is that in
62
subjects with pain the pain threshold in the painful limb is not the same as in the other limb. This lateralization is reduced by TENS. This finding is in agreement with the results of Callaghan et al. [6]. In conclusion ' TENS induces a reset of sensory and of motor systems and a parallel long lasting effect both on sensory and on muscular functions with concomitant pain relief in the pathological subjects. REFERENCES 1 Andersson, S.A. and Holmgren, E., Pain threshold effects of peripheral conditioning stimulation. In: J.J. Bonica and D.G. Albe-Fessard (Eds.), Advances in Pain Research and Therapy, Voi. 1, Raven Press, New York, 1976, pp. 761--768. 2 Barnes, C.O. and Pompeiano, O., Presynaptic and postsynaptic effects in the monosynaptic reflex pathway to extensor motoneurons following vibration of synergic muscles, Arch. ital. Biol., 108 (1970) 259--294. 3 Bathien, N., Rdflexes spinaux chez l'homme et niveaux d'attention, Electroenceph. clin. Neurophysiol., 30 (1971) 32--37. 4 Bathien, N. et Hugelin~ A., R~flexes monosynaptiques et polysynaptiques de l'homme au cours de l'attention, Electroenceph. clin. Neurophysiol., 26 (1969) 605--612. 5 Brunia, C.H.M., Effect of propranolol on monosynaptic reflex activity during task, Appl. Neurophysiol., 42 (1979) 135--144. 6 Callaghan, M., Sternbach, R.A., Nyquist, J.K. and Timrnermans, G., Changes in somatic ,sensitivity during transcutaneous electrical analgesia, Pain, 5 (1978) 115-127. 7 Della Corte, M., Procacci, P., Bozza, G. and Buzzelli, G., A study on the cutaneous pricking pain threshold in normal man, Arch. Fisiol., 64 (1965) 141--170. 8 Delwaide, P.J., Human monosynaptic reflexes and presynaptic inhibition. In: J.E. Desmedt (Ed.), New Developments in Electromyography and Clinical Neurophysiology, Vol. 3, Karger, Basel, 1973, pp. 508--522. 9 Eriksson, M.B.E. and Sjblund, B.H., Acupuncture-like electroanalgesia in TNSresistant chronic pain. In: Y. Zotterman (Ed.), Sensory Functions of the Skin, Pergamon Press, Oxford, 1976, pp. 575--581. 10 Francini, F. and Maresca, M., Local and generalized changes of the cutaneous sensory thresholds during transcutaneous electrical stimulation (TES) in healthy subjects and in patients with chronic pain. In: Pain Abstracts, Vol. I, International Association for the Study of Pain, Seattle, Wash., 1978, p. 127. 11 Francini, F., Procacci, P., Zoppi, M. and Maresca, M., Mechanisms of action of transcutaneous ele~'trical stimulation (TES) for relief of pain (electroanalgesia), Neurosci. Lett., Suppl. ~ (1978) 431. 12 Francini, F., Z~ppi, M., Maresca, M. and Procacci, P., Skin potential and EMG changes induced by cutaneous electrical stimulation. I. Normal man in arousing and non-arousing, environment, Appl. Neurophysiol., 42 (1979) 113--124. 13 Gassel, M.M. and Diarnantopoulos, E., Nerve potential recordings during electrically and mechanically evoked monosynaptic reflexes in man, Nature (Lond.), 208 (1965) 1004--1005. 14 Hiedl, P., Struppler, A. and Gessler, M.. TNS-evoked long loop effects, Appl. Neurophysiol., 42 (1979) 153--159. 15 Hugon, M., Methodology of the Hoffmann reflex in man. In: J.E. Desmedt (Ed.), New Developments in Flectromyography and Clinical Neurophysiology, Vol. 3, Karger, Basel, 1973, pp. 277--293. 16 Lindblom, U. and Meyerson, B.A., Influence on touch, vibration and cutaneous pain of dorsal column stimulation in man, Pain, 1 (1975) 257--270.
63 17 Long, D.M. and Hagfors, N., Electrical stimulation in the nervous system: the current status of electrical stimulation of the nervous system for relief of pain, Pain, 1 (1975) 109--123. 18 Pompeiano, O., Reticular formation. In: A. Iggo (Ed.), Handbook of Sensory Physiology, Somatosensory System, Vol. II, Springer, Berlin, 1973, pp. 393--415. 19 Procacci, P., Francini, F., Zoppi, M. and Maresca, M., Cutaneous pain threshold changes after sympathetic block in reflex dystrophies, Pain, 1 (1975) 167--175. 20 Procacci, P., Zoppi, M. e Maresca, M., La terapia delle sindromi dolorose con stimolazione elettrica (elettroanalgesia), Clin. Ter., 73 (1975) 465--474. 21 Procacci, P., Zoppi, M., Maresca, M. and Francini, F., Hypoalgesia induced by transcutaneous electrical stimulation. A physiological and clinical investigation, J. neurosurg. Sci., 21 (1977) 221--228. 22 Procacci, P., Francini, F., Maresca, M. and Zoppi, M., Skin potential and EMG changes induced by cutaneous e|~etrlcg! stimulation. II. Subjects with reflex sympathetic dystrophies, Appl. Neuropbysiol., 42 (1979) 125--134. 23 Procacci, P., Zoppi, M., Francini, F , Maresca, M. e Bernardini, U.D., Variazioni locali e generalizzate delle soglie sensitive cutanee durante stimolazione elettrica transcutanea in soggetti normali e in pazienti con dolore cronico. In: C.A. Pagni, P. Procacci and V. Ventafridda (Eds.), II l~olore, Problemi di Fisiopatologia e Terapia, Edizioni Cortina, Verona, 1979, pp. 135--146. 24 Taub, A. and Campbell, J.N., Percutaneous local electrical analgesia: peripheral mechanisms. In: J.J. Bonica (Ed.), Advances in Neurology, Vol. 4, Raven Press, New York, 1974, pp. 733--736.