Journal of
J. Neurol. 217, 261--270 (1978)
Neurology © by Springer-Verlag 1978
Pain Perception in Man after Long Term Spinal Cord Stimulation* M. Doerr 1, J.-U. Krainick 2, and U. Thoden 1
1Department of Clinical Neurology and Neurophysiology, University of Freiburg/Breisgau, Hansastrage 9, D-7800 Freiburg, Federal Republic of Germany, and 2Department of Stereotactic Neurosurgery, University of Saarland, D-6650 Homburg/Saar, Federal Republic of Germany
Summary. Thresholds of non-painful and painful perception for electrical stimuli are not altered significantly during dorsal column stimulation either in the area of induced paresthesia or outside it. After long term stimulation of the dorsal column the thresholds for stimuli are significantly higher within the area of induced paresthesia but not outside it. Median nerve evoked somatosensory cortical potentials are not altered by conditioning or simultaneous DC stimulation. During DCS in three of eight patients only the vibration evoked cortical potentials were attenuated in the early three components of the potential. Key words: Dorsal column stimulation in man - DCS - Pain suppression, electrical - Somatosensory evoked cortical potentials - Threshold measurements.
Zusammenfassung. Empfindungs- und Schmerzschwellen elektrischer Reize werden bei gleichzeitiger elektrischer Hinterstrangstimulation weder im Gebiet der iiberdeckten Reizparfisthesien noch augerhalb derselben ver~indert empfunden. Nach l~tngerer, im Durchschnitt mehrmonatiger elektrischer Hinterstrangreizung (DCS : d o r s a l column stimulation) sind beide Schwellen im Ausbreitungsgebiet der Reizpar~isthesien signifikant h6her. Somatosensible evozierte Hirnrindenpotentiale nach elektrischem Medianusreiz sind weder durch konditionierende noch durch gleichzeitige Hinterstrangreizung zu verfindern. Lediglich durch Vibration evozierte Hirnrindenpotentiale zeigen unter Hinterstrangreizung eine Abflachung der frtihen Potentialkomponenten 1--3. * Supported by Sonderforschungsbereich Hirnforschung und Sinnesphysiologie(SFB 70) der Deutschen Forschungsgemeinschaft (DFG) and Bundesminister fiir Arbeit und Sozialordnung
0340-5354/78/0217/0261/$02.00
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A c c o r d i n g to the g a t e c o n t r o l t h e o r y o f p a i n [20], a n d r e l a t e d t h e o r i e s [12], p a i n s e n s a t i o n s h o u l d be i n h i b i t e d d u r i n g electrical s t i m u l a t i o n o f fast fiber s y s t e m s in p e r i p h e r a l n e r v e s o r the d o r s a l c o l u m n s y s t e m o f the spinal cord. O n this basis several clinical m e t h o d s o f m o d u l a t i n g p a i n by electrical s t i m u l a t i o n , such as 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 ) [4, 5, 19, 26, 27], a n d d o r s a l c o l u m n s t i m u l a t i o n ( D C S ) , h a v e y i e l d e d f a v o r a b l e clinical results. G o o d relief o f p a i n is seen m a p to 60% o f i n t r a c t a b l e c h r o n i c p a i n states a f t e r D C S [10, 11, 13, 14, 15, t6, 21, 24, 28]. T h i s p a p e r a i m s to i n v e s t i g a t e the i n f l u e n c e o f D C S o n n o n - p a i n f u l a n d p a i n f u l p e r c e p t i o n d u r i n g s h o r t a n d a f t e r l o n g s t i m u l a t i o n o f the d o r s a l c o l u m n s ( D C S ) , as well as the i n f l u e n c e o f c o n d i t i o n i n g o r s i m u l t a n e o u s D C s t i m u l a t i o n on s o m a t o s e n s o r y e v o k e d c o r t i c a l p o t e n t i a l s .
Methods and Materials The stimulus intensities of median nerve stimulation for the thresholds of non-painful and painful perception were studied before and during dorsal column stimulation (DCS) in eight patients 1 or 2 days after the insertion of spinal 'floating' test electrodes (Medtronic) and before implantation of the final electrode, and in eight patients with final electrode systems (Medtronic), implanted for post amputation pain. This implantation had been performed from 11 days to 9 months earlier (average 3 months). Somatosensory evoked cortical potentials (ssep) were recorded in 25 further patients with permanent DCS electrodes implanted for chronic intractable pain: 24 for post amputation pain, one for pain after a brachial plexus lesion. They were all males, ranging in age between 35--60 years. All patients reported good relief of pain with the use of these stimulators. Moreover in all these 25 patients the projection of the paraesthesias induced could be changed by altering the stimulation parameter [15, 16]. Threshold Measurements. The skin was stimulated electrically with single rectangular pulses (0.1 to 10 msec). Stimulation was triggered by hand to avoid expectation of a regularly occurring stimulus on the part of the patient. Silver-silverchloride electrodes of 7 mm diameter were fixed with adhesive tape with the indifferent electrode (4 x 6 cm) always on the thigh. Electrical stimuli were always applied to three areas: a) the trigeminal area, which was in all cases outside the DC induced paraesthesia, b) an extremity outside the paraesthesia, and c) another extremity, usually the amputation stump, where the paraesthesia was felt. The threshold intensities for perception and pain sensation were determined three times at all these points with average values before and during spinal cord stimulation. Because of the small number of subjects and the high interindividual variation the medians were plotted in the diagrams [25]. Dorsal column stimulation is established as a method for relieving chronic intractable pain,
described elsewhere [13, 16]. The floating electrodes in the spinal subdural space were used over a period of 2 days to ensure the .success of the final implantation [10, 13]. For the threshold study the ~pinal cord was stimulated with the frequency and intensity which produced the best pain relief in the individual patient [15]. To record cortical evoked potentials the median nerve at the wrist was stimulated bipolarly with single rectangular pulses of 0.2 msec duration, with a frequency of 0.5 Hz and an intensity at the motor threshold of the thenar muscle~. Stimulator Type D, T6nnies Freiburg BRD
Pain Perception in Man after Long Term Spinal Cord Stimulation
263
Vibration stimuli were applied by a mechano-stimulator (Burchard Ebringen). For stimulation the hand was fixed in a cast, and a pin with a diameter of 1 mm was brought in contact with the skin over the metacarpal bone. The pressure was servo-controlled at constant level. Trains of vibration between 10--50 msec were used with a frequency of 250 Hz and single pulses of 3 msec duration. These trains were repeated every three seconds. For the recording of somatosensoryevoked corticalpotentials (ssep) patients sat comfortably in a chair with the head on a rest, the eyes closed, and the ears plugged. The technic of recording by the Shagass method [23] has been described previously [26]. /50 EEG responses were averaged over 500 msec (CAT 400 averager). The terminology of Broughton et al. [3] was used characterizing the ssep.
Results
Perception and Pain Thresholds a) Spinal Floating Electrodes. The m e d i a n s o f the t h r e s h o l d values for p e r c e p t i o n a n d p a i n f u l sensation o f electrical stimuli in the areas covered by the p a r aesthesias i n d u c e d b e f o r e a n d d u r i n g spinal c o r d s t i m u l a t i o n are r e p r e s e n t e d in F i g u r e l a . B o t h t h r e s h o l d s were n o t significantly altered d u r i n g spinal c o r d stimulation. T h e s a m e results were f o u n d in the areas tested o u t s i d e the i n d u c e d p a r aesthesias (Fig. l b ) . The m e d i a n values o f the i n d i v i d u a l t h r e s h o l d s inside a n d o u t s i d e the p a r aesthetic a r e a are c o m p a r e d in F i g u r e I c. T h e t h r e s h o l d levels were similar in b o t h o f these areas.
b) Permanently Implanted Dorsal Column Electrodes. F i g u r e 2 shows that the t h r e s h o l d s for p e r c e p t i o n a n d p a i n m e a s u r e d before a n d d u r i n g spinal c o r d s t i m u l a t i o n were n o t c h a n g e d significantly either in the a r e a o f i n d u c e d p a r aesthesia o r o u t s i d e it. But if the m e d i a n s o f the i n d i v i d u a l t h r e s h o l d s are c o m p a r e d for these two areas, all t h r e s h o l d s inside the a r e a o f i n d u c e d p a r aesthesia are significantly higher (Fig. 2c). In these five cases increased t h r e s h o l d s for p e r c e p t i o n a n d p a i n f u l stimuli do n o t always c o r r e l a t e with the subjective relief o f c h r o n i c pain, as r e p o r t e d b y the patients.
Somatosensory Evoked Cortical Potentials (SSEP) a) M e d i a n nerve e v o k e d sseps c o n d i t i o n e d by a single d o r s a l c o l u m n stimulus are d e m o n s t r a t e d in F i g u r e 3 in a p a t i e n t with an electrode p l a c e d at Th4. F i g u r e 3 a shows the ssep o f a single d o r s a l c o l u m n stimulus, 3 b t h a t o f the m e d i a n nerve alone. In F i g u r e 3c the two stimuli are given together. T h e resulting p o t e n t i a l seems to be a s u m m a t i o n o f b o t h single p o t e n t i a l s (Fig. 3a, b). W i t h increasing d e l a y in the m e d i a n nerve stimulus b o t h sseps c o r r e s p o n d i n g l y increase to reach their o r i g i n a l f o r m after 30 msec (Fig. 3 d - - f ) .
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b) The median nerve evoked ssep during continuous dorsal column stimulation, including the stimulated wrist in the induced paraesthesia, is shown in Figure 4. The control ssep (Fig. 4a) is neither changed by a slight nor a maximal, just tolerable, DC stimulus. A very slight increase in the latency of the positive potential wave 4 cannot be excluded, whereas the initial components of the ssep are identical. Similar results were recorded in seven other patients after median nerve stimulation and in two patients after stimulation of the ulnar nerve. c) The vibration evoked ssep during continuous spinal cord stimulation covering the vibrated area of the hand shows a clear depression of the first components 1--3 in parallel with subjectively diminished perception. The inhibition increases with increasing strength of D C stimulation. In contrast the positive component 4 remains unchanged. Similar results were found in two other patients but in five other cases no significant alteration was found in the vibration evoked ssep during continuous DCS.
Discussion According to current pain theories [12, 20] the electrical stimulation of fast fiber systems in peripheral nerves or in the dorsal column system of the spinal cord
Pain Perception in Man after Long Term Spinal Cord Stimulation
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should suppress acute and chronic pain sensation. Relief of chronic intractable pain was found in about 60% of patients by the chronic stimulation of the dorsal column system with implanted electrode systems [14, 19]. Moreover it has been reported that acute pain phenomena are also diminished by transcutaneous peripheral nerve stimulation [11, 26]. To explain this modulation of chronic and acute pain, spinal inhibition of incoming pain signals in the substantia gelatinosa was assumed [12, 20]. Further investigations demonstrate that DCS interferes with the activation of spinothalamic tract cells at least in the spinal cord of the monkey [7]. A similar modulation circuit is assumed for thalamic structures. Bantli et ai. [1] demonstrated in monkeys that dorsal column stimulation could alter responses evoked in supraspinal nuclei through pathways in the ventral quadrants of the spinal cord. From theoretical considerations, based on animal experiments, it may be assumed that, in man also, thresholds for cutaneous sensation and painful stimuli will be increased during fast fiber stimulation. However this supposed shift in thresholds could not be demonstrated experimentally during DCS [8, 18] or TNS [22, 26].
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In contrast to these negative observations during acute DCS a significant increase in the thresholds for first perception and painful sensation of electrical stimuli is found in the area of the projected paraesthesia after DCS stimulation lasting at least several weeks. This increased threshold cannot be explained by the chronic pain state itself, as it is not found with floating electrodes in patients with chronic pain. Since these increased thresholds are only found after long DCS and only in the area of stimulation paraesthesia, a long lasting neuronal inhibition of the pain conducting system by dorsal column stimulation is ol3en to discussion. Humoral mechanisms as described by Fields et al. [6] could not explain this circumscribed shift in cutaneous thresholds. A localized tissue reaction around the implanted electrodes would only result in an interruption in dorsal column conduction, but not of conduction in the contralateral spinothalamic tract. Sseps recorded during and after DCS have been described by several groups. During DCS a nearly complete attentuation of all the initial components up to 200 msec [9, 17] was observed, as well as reduction of only the late components after the first 150 msec [2]. On the other hand our own observations of ssep during DCS show no influence on potentials evoked by electrical stimulation of the median or ulnar nerve. Only vibration evoked cortical potentials are inhibited in the first 3 ssep components in three of eight patients, thus demonstrating a possible block of conduction in the dorsal column system by electrical stimulation. To explain the clinical observation of pain relief in about 60% of patients with chronic pain only the observation of a shifted threshold level after long lasting DCS is acceptable. The observation, that acute DCS is not able to change the thresholds of painful and non-painful perception is inconsistant with the assumption of the gate control theory, which postulates that the effect of cutaneous inputs to the spinal cord is determined by the preceding balance of the activity of large and small afferent nerve fibers. As discussed in a previous paper [26], in which similar results for acute TNS were reported, simultaneous electrical stimulation of all afferent nerve fibers is probably not comparable to natural pain stimuli with its temporal-spatial pattern. A change of single components of the whole afferent volley during natural pain stimuli may lead to a distortion of the pain signal, with a consequent change in pain perception. However the synchronous volley evoked by electrical nerve stimulation is perceived unchanged, despite the dorsal column stimulus. Probably this signal is better focused by expectation of the subject. Nathan and Rudge [22] suggested that the phenomena of attention and distraction could help to explain the pain relieving effects of non-painful stimulation of large afferent fibers. They believed it more difficult to concentrate on either the painful stimulus or the peripheral TNS when they are both in the same area. Although attention plays a dominant role in all perception and threshold experiments, we could not find any difference in threshold estimation if the test stimuli were applied in the paraesthetic area or outside of it. Even if some of the facts, demonstrated in this paper, are inconsistent with the gate control theory, the favorable clinical results of DCS are in no way diminished by our laboratory findings.
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References 1. Bantli, H., Bloedel, J. R., Thienprasit, P.: Supraspinal interactions resulting from experimental dorsal column stimulation. J. Neurosurg. 42, 296--300 (1975) 2. Blair, R. D., Lee, G., Vanderlinden, G.: Dorsal column stimulation. Its effect on the somatosensory evoked response. Arch. Neurol. 32, 826--829 (1975) 3. Broughton, R., Meier-Ewert, K. H., Ebe, M.: Evoked visual somatosensory and retinal potentials in photosensitive epilepsy. Electroenceph. clin. Neurophysiol. 27, 373--386 (1969) 4. Burton, C. L., Maurer, D. D.: Pain suppression by transcutaneous electric stimulation. JEEE Trans. Bio.-Med. Engineering, BME 21, 81 (1974) 5. Ebersold, M. J., Laws, E. R. jr., Stonnington, H. H., Stillwell, G. K.: Transcutaneous electrical stimulation for treatment of chronic pain: A preliminary report. Surg. Neurol. 4, 96--99 (1975) 6. Fields, H. L., Anderson, S. D., Clanton, C. H., Basbaum, A. I.: Nucleus raphe-magnus: A common mediator of opiate- and stimulus-produced analgesia. Trans. Amer. Neurol. Ass. 101,208--210 (1976) 7. Foreman, R. D., Beall, J. E., Applebaum, A. E., Coulter, J. C., Willis, W. D.: Inhibition of primate spinothalamic tract neurons by electrical stimulation of dorsal column or peripheral nerve. Adv. Pain Research and Therapy Vol. 1,405--410. Ed. J. J. Bonica and D. AlbeFessard. New York: Raven 1976 8. Friedman, H., Nashold, B. S. jr., Somjen, G.: Physiological effects of dorsal column stimulation. Adv. Neurol. 4, 769--773 (1974) 9. Grieshop, J., Goldstein, F. P., Larson, S. J.: Spinal electroanaesthesia: Its relationship to somatosensory cerebral evoked potentials. In: Wagender, F. M., Schuy, S. T. (ed.) Electrotherapeutic sleep and Electroanaesthesia. Amsterdam: Excerpta Medica 2, 33--37 (1970) 10. Hosobuci, Y., Adams, J. E., Weinstein, P. R.: Preliminary percutaneous dorsal column stimulation prior to permanent implantation. Amer. Ass. Neurol. Surg. Meeting 1971 11. Hymes, A. C., Raab, D. E., Yonehiro, E. G., Nelson, G. D. and Printy, A. L.: Acute pain control by electrostimulation: A preliminary report. Adv. Neurol. 4, 761--767 (1974) 12. Kerr, F. W. L.: Pain: a central inhibitory balance theory. Mayo Clin. Proc. 50, 685--690 (1975) 13. Krainick, J. U.: Hinterstrangrejzung tiber implantierte Elektroden. Klinische und experimentelle Untersuchungen. Habilitationsscbrift, Freiburg i. Br. 1975 14. Krainick, J. U., Thoden, U.: Electrical stimulation of the spinal cord for the relief of pain. M e t h o d - - p a t i e n t selection--clinical results Adv. Neurosurg. 4, 210--215 (1975) 15. Krainick, J. U., Thoden, U., Riechert, T., Tenschert, G.: Elektrische Hinterstrangreizung bei chronischen Schmerzen. Klinische Erfahrungen fiber zwei Jahre. Neurochirurgia 17, 162--170 (1974) 16. Krainick, J. U., Thoden, U., Riechert, T.: Spinal cord stimulation in post amputation pain. Surg. Neurol. 4, 167--t70 (1975) 17. Larson, S. J., Sances, A. jr., Riegel, D. H., Meyer, G. A., Dallmann, D. E., Swiontek, T.: Neurophysiological effects of dorsal column stimulation in man and monkey. J. Neurosurg. 41, 217--223 (1974) 18. Lindblom, U., Meyerson, B. A.: Influence on touch, vibration and cutaneous pain of dorsal column stimulation in man. Pain 1, 257--270 (1975) 19. Long, D. M.: Use of peripheral and spinal cord stimulation in the relief of chronic pain. Adv. Pain Res. and Therapy Vol. 1. Ed. J. J. Bonica and D. Albe-Fessard. New York: Raven 1976 20. Melzack, R., Wall, P. D.: Pain mechanisms: A new theory. Science 150, 971--979 (1965) 21. Nashold, B. S., Friedmann, H.: Dorsal column stimulation for control of pain. J. Neurosurg. 36, 590--597 (1972) 22. Nathan, P. W., Rudge, P.: Testing the gate control theory of pain in man. J. Neurol. Neurosurg. Psychiat. 37, 1366--1372 (1974) 23. Shagass, C., Schwartz, M.: Recovery functions of somatosensory peripheral nerve and cerebral evoked responses in man. Electroenceph. clin. Neurophysiol. 17, 126--135 (1964) 24. Shealy, C. N., Mortimer, J. T., Hagfors, N. R.: Dorsal column etectroanalgesia. J. Neurosurg. 32, 560--564 (1970)
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25. Siegel, S.: Nonparametric statistics for the behaviour sciences. New York, Toronto, London: McGraw-Hill 1956 26. Strassburg, M. M., Krainick, J. U., Thoden, U.: Influence of transcutaneous nerve stimulation (TNS) on acute pain. J. Neurol. 217, l m l 0 (1977) 27. Thoden, U., Krainick, J. U.: Ambulante Schmerzbehandlung durch transkutane Nervenstimulation. Dtsch. med. Wschr. 99, 1692--1693 (1974) 28. Wall, P. D., Sweet, W. H.: Temporary abolition of pain in man. Science 155, 108--109 (1967)
Received August 23, 1977
J. Neurol. 217, 261--270 (1978)
Neurology © by Springer-Verlag 1978
Pain Perception in Man after Long Term Spinal Cord Stimulation* M. Doerr 1, J.-U. Krainick 2, and U. Thoden 1
1Department of Clinical Neurology and Neurophysiology, University of Freiburg/Breisgau, Hansastrage 9, D-7800 Freiburg, Federal Republic of Germany, and 2Department of Stereotactic Neurosurgery, University of Saarland, D-6650 Homburg/Saar, Federal Republic of Germany
Summary. Thresholds of non-painful and painful perception for electrical stimuli are not altered significantly during dorsal column stimulation either in the area of induced paresthesia or outside it. After long term stimulation of the dorsal column the thresholds for stimuli are significantly higher within the area of induced paresthesia but not outside it. Median nerve evoked somatosensory cortical potentials are not altered by conditioning or simultaneous DC stimulation. During DCS in three of eight patients only the vibration evoked cortical potentials were attenuated in the early three components of the potential. Key words: Dorsal column stimulation in man - DCS - Pain suppression, electrical - Somatosensory evoked cortical potentials - Threshold measurements.
Zusammenfassung. Empfindungs- und Schmerzschwellen elektrischer Reize werden bei gleichzeitiger elektrischer Hinterstrangstimulation weder im Gebiet der iiberdeckten Reizparfisthesien noch augerhalb derselben ver~indert empfunden. Nach l~tngerer, im Durchschnitt mehrmonatiger elektrischer Hinterstrangreizung (DCS : d o r s a l column stimulation) sind beide Schwellen im Ausbreitungsgebiet der Reizpar~isthesien signifikant h6her. Somatosensible evozierte Hirnrindenpotentiale nach elektrischem Medianusreiz sind weder durch konditionierende noch durch gleichzeitige Hinterstrangreizung zu verfindern. Lediglich durch Vibration evozierte Hirnrindenpotentiale zeigen unter Hinterstrangreizung eine Abflachung der frtihen Potentialkomponenten 1--3. * Supported by Sonderforschungsbereich Hirnforschung und Sinnesphysiologie(SFB 70) der Deutschen Forschungsgemeinschaft (DFG) and Bundesminister fiir Arbeit und Sozialordnung
0340-5354/78/0217/0261/$02.00
262
M. Doerr et al.
A c c o r d i n g to the g a t e c o n t r o l t h e o r y o f p a i n [20], a n d r e l a t e d t h e o r i e s [12], p a i n s e n s a t i o n s h o u l d be i n h i b i t e d d u r i n g electrical s t i m u l a t i o n o f fast fiber s y s t e m s in p e r i p h e r a l n e r v e s o r the d o r s a l c o l u m n s y s t e m o f the spinal cord. O n this basis several clinical m e t h o d s o f m o d u l a t i n g p a i n by electrical s t i m u l a t i o n , such as 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 ) [4, 5, 19, 26, 27], a n d d o r s a l c o l u m n s t i m u l a t i o n ( D C S ) , h a v e y i e l d e d f a v o r a b l e clinical results. G o o d relief o f p a i n is seen m a p to 60% o f i n t r a c t a b l e c h r o n i c p a i n states a f t e r D C S [10, 11, 13, 14, 15, t6, 21, 24, 28]. T h i s p a p e r a i m s to i n v e s t i g a t e the i n f l u e n c e o f D C S o n n o n - p a i n f u l a n d p a i n f u l p e r c e p t i o n d u r i n g s h o r t a n d a f t e r l o n g s t i m u l a t i o n o f the d o r s a l c o l u m n s ( D C S ) , as well as the i n f l u e n c e o f c o n d i t i o n i n g o r s i m u l t a n e o u s D C s t i m u l a t i o n on s o m a t o s e n s o r y e v o k e d c o r t i c a l p o t e n t i a l s .
Methods and Materials The stimulus intensities of median nerve stimulation for the thresholds of non-painful and painful perception were studied before and during dorsal column stimulation (DCS) in eight patients 1 or 2 days after the insertion of spinal 'floating' test electrodes (Medtronic) and before implantation of the final electrode, and in eight patients with final electrode systems (Medtronic), implanted for post amputation pain. This implantation had been performed from 11 days to 9 months earlier (average 3 months). Somatosensory evoked cortical potentials (ssep) were recorded in 25 further patients with permanent DCS electrodes implanted for chronic intractable pain: 24 for post amputation pain, one for pain after a brachial plexus lesion. They were all males, ranging in age between 35--60 years. All patients reported good relief of pain with the use of these stimulators. Moreover in all these 25 patients the projection of the paraesthesias induced could be changed by altering the stimulation parameter [15, 16]. Threshold Measurements. The skin was stimulated electrically with single rectangular pulses (0.1 to 10 msec). Stimulation was triggered by hand to avoid expectation of a regularly occurring stimulus on the part of the patient. Silver-silverchloride electrodes of 7 mm diameter were fixed with adhesive tape with the indifferent electrode (4 x 6 cm) always on the thigh. Electrical stimuli were always applied to three areas: a) the trigeminal area, which was in all cases outside the DC induced paraesthesia, b) an extremity outside the paraesthesia, and c) another extremity, usually the amputation stump, where the paraesthesia was felt. The threshold intensities for perception and pain sensation were determined three times at all these points with average values before and during spinal cord stimulation. Because of the small number of subjects and the high interindividual variation the medians were plotted in the diagrams [25]. Dorsal column stimulation is established as a method for relieving chronic intractable pain,
described elsewhere [13, 16]. The floating electrodes in the spinal subdural space were used over a period of 2 days to ensure the .success of the final implantation [10, 13]. For the threshold study the ~pinal cord was stimulated with the frequency and intensity which produced the best pain relief in the individual patient [15]. To record cortical evoked potentials the median nerve at the wrist was stimulated bipolarly with single rectangular pulses of 0.2 msec duration, with a frequency of 0.5 Hz and an intensity at the motor threshold of the thenar muscle~. Stimulator Type D, T6nnies Freiburg BRD
Pain Perception in Man after Long Term Spinal Cord Stimulation
263
Vibration stimuli were applied by a mechano-stimulator (Burchard Ebringen). For stimulation the hand was fixed in a cast, and a pin with a diameter of 1 mm was brought in contact with the skin over the metacarpal bone. The pressure was servo-controlled at constant level. Trains of vibration between 10--50 msec were used with a frequency of 250 Hz and single pulses of 3 msec duration. These trains were repeated every three seconds. For the recording of somatosensoryevoked corticalpotentials (ssep) patients sat comfortably in a chair with the head on a rest, the eyes closed, and the ears plugged. The technic of recording by the Shagass method [23] has been described previously [26]. /50 EEG responses were averaged over 500 msec (CAT 400 averager). The terminology of Broughton et al. [3] was used characterizing the ssep.
Results
Perception and Pain Thresholds a) Spinal Floating Electrodes. The m e d i a n s o f the t h r e s h o l d values for p e r c e p t i o n a n d p a i n f u l sensation o f electrical stimuli in the areas covered by the p a r aesthesias i n d u c e d b e f o r e a n d d u r i n g spinal c o r d s t i m u l a t i o n are r e p r e s e n t e d in F i g u r e l a . B o t h t h r e s h o l d s were n o t significantly altered d u r i n g spinal c o r d stimulation. T h e s a m e results were f o u n d in the areas tested o u t s i d e the i n d u c e d p a r aesthesias (Fig. l b ) . The m e d i a n values o f the i n d i v i d u a l t h r e s h o l d s inside a n d o u t s i d e the p a r aesthetic a r e a are c o m p a r e d in F i g u r e I c. T h e t h r e s h o l d levels were similar in b o t h o f these areas.
b) Permanently Implanted Dorsal Column Electrodes. F i g u r e 2 shows that the t h r e s h o l d s for p e r c e p t i o n a n d p a i n m e a s u r e d before a n d d u r i n g spinal c o r d s t i m u l a t i o n were n o t c h a n g e d significantly either in the a r e a o f i n d u c e d p a r aesthesia o r o u t s i d e it. But if the m e d i a n s o f the i n d i v i d u a l t h r e s h o l d s are c o m p a r e d for these two areas, all t h r e s h o l d s inside the a r e a o f i n d u c e d p a r aesthesia are significantly higher (Fig. 2c). In these five cases increased t h r e s h o l d s for p e r c e p t i o n a n d p a i n f u l stimuli do n o t always c o r r e l a t e with the subjective relief o f c h r o n i c pain, as r e p o r t e d b y the patients.
Somatosensory Evoked Cortical Potentials (SSEP) a) M e d i a n nerve e v o k e d sseps c o n d i t i o n e d by a single d o r s a l c o l u m n stimulus are d e m o n s t r a t e d in F i g u r e 3 in a p a t i e n t with an electrode p l a c e d at Th4. F i g u r e 3 a shows the ssep o f a single d o r s a l c o l u m n stimulus, 3 b t h a t o f the m e d i a n nerve alone. In F i g u r e 3c the two stimuli are given together. T h e resulting p o t e n t i a l seems to be a s u m m a t i o n o f b o t h single p o t e n t i a l s (Fig. 3a, b). W i t h increasing d e l a y in the m e d i a n nerve stimulus b o t h sseps c o r r e s p o n d i n g l y increase to reach their o r i g i n a l f o r m after 30 msec (Fig. 3 d - - f ) .
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b) The median nerve evoked ssep during continuous dorsal column stimulation, including the stimulated wrist in the induced paraesthesia, is shown in Figure 4. The control ssep (Fig. 4a) is neither changed by a slight nor a maximal, just tolerable, DC stimulus. A very slight increase in the latency of the positive potential wave 4 cannot be excluded, whereas the initial components of the ssep are identical. Similar results were recorded in seven other patients after median nerve stimulation and in two patients after stimulation of the ulnar nerve. c) The vibration evoked ssep during continuous spinal cord stimulation covering the vibrated area of the hand shows a clear depression of the first components 1--3 in parallel with subjectively diminished perception. The inhibition increases with increasing strength of D C stimulation. In contrast the positive component 4 remains unchanged. Similar results were found in two other patients but in five other cases no significant alteration was found in the vibration evoked ssep during continuous DCS.
Discussion According to current pain theories [12, 20] the electrical stimulation of fast fiber systems in peripheral nerves or in the dorsal column system of the spinal cord
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should suppress acute and chronic pain sensation. Relief of chronic intractable pain was found in about 60% of patients by the chronic stimulation of the dorsal column system with implanted electrode systems [14, 19]. Moreover it has been reported that acute pain phenomena are also diminished by transcutaneous peripheral nerve stimulation [11, 26]. To explain this modulation of chronic and acute pain, spinal inhibition of incoming pain signals in the substantia gelatinosa was assumed [12, 20]. Further investigations demonstrate that DCS interferes with the activation of spinothalamic tract cells at least in the spinal cord of the monkey [7]. A similar modulation circuit is assumed for thalamic structures. Bantli et ai. [1] demonstrated in monkeys that dorsal column stimulation could alter responses evoked in supraspinal nuclei through pathways in the ventral quadrants of the spinal cord. From theoretical considerations, based on animal experiments, it may be assumed that, in man also, thresholds for cutaneous sensation and painful stimuli will be increased during fast fiber stimulation. However this supposed shift in thresholds could not be demonstrated experimentally during DCS [8, 18] or TNS [22, 26].
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In contrast to these negative observations during acute DCS a significant increase in the thresholds for first perception and painful sensation of electrical stimuli is found in the area of the projected paraesthesia after DCS stimulation lasting at least several weeks. This increased threshold cannot be explained by the chronic pain state itself, as it is not found with floating electrodes in patients with chronic pain. Since these increased thresholds are only found after long DCS and only in the area of stimulation paraesthesia, a long lasting neuronal inhibition of the pain conducting system by dorsal column stimulation is ol3en to discussion. Humoral mechanisms as described by Fields et al. [6] could not explain this circumscribed shift in cutaneous thresholds. A localized tissue reaction around the implanted electrodes would only result in an interruption in dorsal column conduction, but not of conduction in the contralateral spinothalamic tract. Sseps recorded during and after DCS have been described by several groups. During DCS a nearly complete attentuation of all the initial components up to 200 msec [9, 17] was observed, as well as reduction of only the late components after the first 150 msec [2]. On the other hand our own observations of ssep during DCS show no influence on potentials evoked by electrical stimulation of the median or ulnar nerve. Only vibration evoked cortical potentials are inhibited in the first 3 ssep components in three of eight patients, thus demonstrating a possible block of conduction in the dorsal column system by electrical stimulation. To explain the clinical observation of pain relief in about 60% of patients with chronic pain only the observation of a shifted threshold level after long lasting DCS is acceptable. The observation, that acute DCS is not able to change the thresholds of painful and non-painful perception is inconsistant with the assumption of the gate control theory, which postulates that the effect of cutaneous inputs to the spinal cord is determined by the preceding balance of the activity of large and small afferent nerve fibers. As discussed in a previous paper [26], in which similar results for acute TNS were reported, simultaneous electrical stimulation of all afferent nerve fibers is probably not comparable to natural pain stimuli with its temporal-spatial pattern. A change of single components of the whole afferent volley during natural pain stimuli may lead to a distortion of the pain signal, with a consequent change in pain perception. However the synchronous volley evoked by electrical nerve stimulation is perceived unchanged, despite the dorsal column stimulus. Probably this signal is better focused by expectation of the subject. Nathan and Rudge [22] suggested that the phenomena of attention and distraction could help to explain the pain relieving effects of non-painful stimulation of large afferent fibers. They believed it more difficult to concentrate on either the painful stimulus or the peripheral TNS when they are both in the same area. Although attention plays a dominant role in all perception and threshold experiments, we could not find any difference in threshold estimation if the test stimuli were applied in the paraesthetic area or outside of it. Even if some of the facts, demonstrated in this paper, are inconsistent with the gate control theory, the favorable clinical results of DCS are in no way diminished by our laboratory findings.
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Received August 23, 1977
