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Comparison of short-latency trigeminal evoked potentials elicited by painful dental and gingival stimulation
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Electroencephalograpt~v and clinical Neurophysiologv, 1986, 65: 20-26 Elsevier Scientific Publishers Ireland, Ltd.
C O M P A R I S O N O F S H O R T - L A T E N C Y T R I G E M I N A L EVOKED P O T E N T I A L S ELICITED BY PAINFUL DENTAL AND GINGIVAL S T I M U L A T I O N 1 C. R I C H A R D C H A P M A N , REBECCA G E R L A C H , R O B E R T JACOBSON, V E R O N I C A B U F F I N G T O N and ELIEZAR KAUFMANN
Department o[ Anesthesiologo'. University of Washington School of Medicine, Seattle, WA 98195 (U.S.A.) (Accepted for publication: July 1, 1985)
Summary
Painful stimulation of tooth pulp and of the maxillary gingiva was undertaken in 16 volunteers. Short-latency evoked potentials (15-50 msec) were recorded over 800 trials in each case at F3-P3 of F4-P4, and the resultant averaged wave forms were compared. The gingival wave was distinct in all subjects and could be averaged across subjects while the dental waves were either noise or very inconsistent over subjects. Averaging of the dental wave forms across subjects yielded an uninterpretable result. It was clear that dental evoked potentials could not be recorded at these sites. These findings could be explained by either or both of two hypotheses: (1) dental afferents are predominantly small fiber, nociceptive end organs that conduct more slowly than soft tissue afferents whereas gingival stimulation activates both large and small fiber populations; and (2) dental representation in somatosensory cortex is different and phylogenetically more primitive than that of neighboring soft tissue. Therefore, the location of the generator sites in cortex and the orientation of the dipole may be different for dental than for gingival wave forms. Keywords: dental stimulation - trigeminal evoked potentials - gingival stimulation
Evoked potentials (EPs) are attracting increasing attention as possible correlates of experimental pain in man and many investigators have used painful stimulation of the face or oral cavity in such research (reviewed by Chudler and Dong 1983). Most investigations have targeted longlatency wave forms which occur between 50 and 500 msec. The amplitudes of such waves have been reported to correlate with stimulus intensity and subjective reports of pain (Chatrian et al. 1975; Sano 1977; Stowell 1977; Carmon et al. 1978; Harkins and Chapman 1978; Chen et al. 1979; Buchsbaum et al. 1980). In addition, long-latency wave form amplitudes decrease with subjective pain report when an analgesic intervention is given (Chapman and Benedetti 1979; Chapman et al. 1980; Buchsbaum et al. 1981; Gehrig et al. 1981; Schimek et al. 1982; Butler et al. 1983) and doseresponse effects have been demonstrated (Benedetti et al. 1982). Short-latency trigeminal waves occurring 15-50 msec following the stimulus have been studied less I This work has been done with the support of N I D R Program Project DE 05130 and N I N C D S Program Project NS 16329.
pain
extensively in pain research than have later peaks, although there are many reports of short-latency EPs elicited by non-painful electrical or mechanical stimulation of face or mucous membrane. EPs to somatosensory stimulation may prove to be of value in the clinical assessment of neural function in patients since the peak latencies of such wave forms vary with the locus of stimulation and the conduction velocity of peripheral and central neural pathways. Short-latency clinical EP studies have most often been done to evaluate patients with orofacial pain (Bennett and Jannetta 1980; St~3hr et al. 1981; Buettner et al. 1982; Salar et al. 1982). Although peak polarities and latencies may vary across studies as a function of recording electrode placement, these studies show that a characteristic triphasic wave form with peaks at roughly 20, 35 and 45 msec can be observed during electrical stimulation of soft tissue in the face or mouth. Dental short-latency potentials in humans have not been previously reported. Dental pulp afferent innervation is predominantly (though not entirely) from relatively slow conducting, unmyelinated C and small, myelinated A6 fibers. While these fibers appear to serve primarily a nociceptive function,
0168-5597/86/$03.50 © 1986 Elsevier Scientific Publishers Ireland, Ltd.
SHORT-LATENCY EPs ELICITED BY PAINFUL STIMULATION
they are also known to subserve other sensory modalities (Mumford and Bowsher 1976; Byers in press). In addition to nociceptors, dental pulp contains Aft parent axons and sympathetic fibers. The tooth pulp is therefore a predominant, but not a pure nociceptive end organ. On the other hand, the soft tissue of the gingiva contains a large number of relatively fast conducting non-nociceptive A/~ fibers in addition to A6 and C fibers and is therefore only partly nociceptive. Consequently, short-latency potentials elicited by painful dental stimulation should differ from those elicited by painful gingival stimulation if the tooth pulp afferent fiber volley is primarily nociceptive. The cortical short-latency dental wave form should either: (1) show later peak latency than the soft tissue EP due to predominance of slow-conducting fibers; or (2) be less distinct than soft tissue when measured at scalp locations over primary and secondary somatosensory cortex due to differences in cortical representation. The following report compares trigeminal short-latency EPs elicited by painful dental stimulation with those elicited by painful gingival stimulation.
Methods
Subjects Sixteen male and female volunteers (10 men and 6 women) between 21 and 40 years of age served as paid volunteers. All were in good health and free of oral pathology. Each read and signed an informed consent statement approved by the University of Washington Human Subjects Institutional Review Board.
Methods Subjects were seated in a dental chair inside a sound attenuated, electrically shielded chamber. They were monitored by the research technologist through a television and two-way microphone circuit. A variable period of practice was undertaken with each subject to acquaint him or her with the equipment, the sensations of stimulation, and assure good control over location of electrode position. Subjects were tested under two conditions: stimulation of a central incisor and stimulation of
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the maxillary gingiva approximately 1 cm lateral to midline. Stimulation was on the same side in both cases, and the order of the stimulation modalities was counterbalanced across subjects. During the practice period, subjects were required to identify subjectively equal stimulus intensities at dental and gingival sites. There were 800 trials for each stimulus modality. EPs were elicited by repetitive electrical stimulation delivered through a probe that the subject held in place at tooth or gingiva. A stimulator with stimulus isolation and constant current units was used to deliver the electrical stimuli at 150 V at the rate of 1 pulse/2 sec. Dental stimuli were delivered through a 5 mm diameter cylinder of conductive rubber mounted in the hand-held probe. The cathode was held at the edge of a central incisor (Martin and Chapman 1979) and the anode was a Beckman electrode filled with conductive gel that was taped to the skin 0.5 cm lateral to the ala of the nose ipsilateral to the cathode. Gingival stimuli were delivered through 2 metal alloy balls, 1 mm in diameter each, spaced 2 mm apart and mounted in the tip of the hand-held probe. Pulse width was 0.1 msec for gingival stimulation and 2 msec for dental stimuli. Care was taken to avoid contraction of lip or other facial muscles during gingival stimulation. The intraoral electrode was separated from the lip by a cotton dental roll. Subjects were instructed to alert the experimenter to any sensations of muscle contraction. In both cases stimuli were delivered at an intensity that the subject felt to be distinctly but not distressingly painful. For dental stimuli the mean intensity for all subjects was 55 ~A while for gingival stimuli it was 8.60 mA. The sensitivity of the tooth pulp to electrical stimulation is always much greater than that of soft tissue because current density is high in the pulpal chamber. Stimulation was computer controlled.
EP recording Silver recording electrodes were affixed to the scalp with collodion and resistances were kept at or below 5 kI2. Recordings were obtained at either F3-P3 or F4-P4 contralateral to the stimulus with a ground attached to the left zygomatic promi-
22
C.R. CHAPMAN ET AL.
nence. Each sample consisted of 20 msec of base-
~m
l i n e a n d 50 m s e c o f p o s t s t i m u l u s E E G . S i g n a l s were amplified via amplifiers with an effective bandwidth of 0.01-3 kHz. The sampling rate was 7K. The amplified signals were fed into a MINC
,
Lm
/
~m
I. IlI
EI~GK:
Fig. 2. TEP wave forms for 3 subjects shown in Fig. 1. Four successive 200 trial averages elicited by gingival stimulation are shown in the left panel and by dental stimulation in the right panel.
E2P2BB LImI
1.-Io
h
~,,,,,~ll~Jnn~.,,,,
italt
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E2P39B -- I o ImDml - 10 . III
!o
-
L m
-
~'I
• T|4
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Fig. ]. TEP wave forms for 3 typical subjects. Wave form D is elicited by dental stimulation and wave form G by gingival
stimulation.
Fig. 3. a and b: mean dental (a) and gingival (b) wave forms averaged across subjects plus and minus one standard error at the mean.
SHORT-LATENCY EPs ELICITED BY PAINFUL STIMULATION
LSI 11,/23 computer system that provided A / D conversion, and single-trial wave forms were stored on disk and dumped to tape via a Cipher digital tape drive for later off-line analysis. Averages were obtained off-line and hard copy was obtained with a plotter.
Results The EP wave forms for 3 typical subjects in the gingival and dental stimulation conditions are shown in Fig. 1. The two types of waves are superimposed for each of the subjects. Habituation effects over trials were examined for a subsample of subjects. Within subjects stability in these records can be seen in Fig. 2 where plots of 200 trials each are superimposed for each type of stimulus for each of the 3 subjects. When compared across subjects, the gingival wave forms were distinct and consistent in morphology, while dental waves were either absent, indistinct or idiosyncratic with little similarity over individual volunteers. When clearly defined, the dental waves tend to be smaller in amplitude than gingival waves with markedly different peak latency. This can be seen most clearly when the two types of wave forms are averaged across subjects. Fig. 3a and b display the mean (a) gingival, and (b) dental, wave forms averaged across subjects, plus and minus 1 standard error of the mean. The mean gingival wave form demonstrated clearly definable peaks that are consistent with the reports of Bennett and Jannetta (1980) and others. In
Fig. 4. Mean dental TEP (solid line) and mean gingival TEP (dashed line) with 95% confidence interval.
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contrast, the mean dental wave was smaller and barely distinguishable from noise. In addition, the figures show that from roughly 15 to 40 msec the between-subjects variability of the data was somewhat greater in the dental than in the gingival stimulation condition. In Fig. 4 the mean dental wave form is shown with a 95% confidence interval. The gingival wave form (dashed line) is superimposed upon it. It can be seen that the major peaks of the gingival wave differ significantly from the dental data since they lie outside the 95% confidence interval.
Discussion Short-latency EPs elicited by gingival stimulation were clearly defined and consistent with the results of other investigations that have attempted to characterize the short-latency trigeminal wave form associated with soft tissue stimulation in normals. Badr et al. (1983) studied 18 normal volunteers, applying electrodes to the corner of the mouth for stimulation. Recording from a point above somatosensory cortex referred to ear lobe, they reported waves characterized as P20, N30, P40 and N50 with N30 being the most consistent feature. StOhr and Petruch (1979) stimulated 55 normal volunteers on the lip using non-painful electrical stimulation while recording from C5 and C6 with Fz as reference. They reported waves characterized as N13, P19 and N26, with P19 being most prominent. Our observations are also consistent with clinical studies of pain patients. Most have employed painless oral or facial somatosensory stimuli. Singh et al. (1982) stimulated the mental nerve at the mandibular foramen and compared EPs in 7 normals with those seen in 25 patients having chronic facial pain or neurologic abnormalities, recording from P3 or P4 referred to clavicle or mastoid. They observed peaks at P23 and N34, with some abnormalities in patients having cranial nerve palsy or acoustic neuromas. Drechsler (1980) also stimulated mental foramen electrically, recording at F3-C3 or F4-C4. The mean wave form for 20 subjects was characterized by P23, N34 and P44 peaks. Buettner et al. (1982) followed the investi-
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gation noted above by studying EPs elicited by non-painful electrical lip stimulation in tic douloureux patients and reported that P19 latency differed significantly between the normal and affected sides of the face, being later on the involved side. St6hr et al. (1981) examined EPs elicited by lip stimulation in subjects with tic douloureux and found that 41% of 17 patients without prior surgery demonstrated an increased latency for N19 on the involved side. Salar et al. (1982) employed cutaneous electrical stimuli with needle electrodes in trigeminal neuralgia patients before and after percutaneous coagulation of the gasserian ganglion, recording at a point 7 cm from vertex on the vertex-meatus line. They observed a triphasic wave, P20, N35 and P50. EPs varied across patients with reports of sensory loss following surgery, but they did not change as a function of clinical pain. Only Bennett and Jannetta (1980) have used painful stimuli. They electrically stimulated the maxillary gingiva at painful levels on the asymptomatic side in trigeminal neuralgia patients as well as in norreals and sludied the short-latency wave elicited. Scalp recording was done contralateral to the stimulus at the midpoint of a line connecting the auditory meatus and a point 1 cm posterior to vertex with reference to earlobe. The EPs consisted of a triphasic wave form, N20, P34, and N51. These studies show moderately good agreement with one another and with our observations in characterizing the short-latency trigeminal EP elicited by soft tissue stimulation. Only Bennett and Jannetta used painful stimulation. Since their EPs were highly similar to those reported by Badr et al. (1983); Salar et al. (1982), and others mentioned above, their outcomes suggest that pain-related short-latency gingival waves are not different than other somatosensory wave forms elicited from oral soft tissue. Salar et al. (1982) have offered consistent data since their patients showed no differences in short-latency waves as a function of pain sensibility. It is clear from our observations that painful stimulation of tooth pulp and gingival tissue yield different outcomes. Unlike the gingival wave, the amplitude of the dental wave is small when averaged across subjects. As noted above, this result is due to absent, indistinct or idiosyncratic responses
C.R. C H A P M A N ET AL.
for individual subjects and is not a function of averaging distinct large amplitude early wave forms that vary only in latency across subjects. Two hypotheses can be offered to explain this observation. First, the failure of the dental stimulus to elicit a clearly defined wave form within 50 msec may reflect the conduction times of the specific population of sensory end organs stimulated in the tooth pulp. It is probable that dental stimulation at submaximal intensities activates mainly A6 rather than C fibers since the sensations elicited are discrete and not slow or lingering. These fibers have slower conduction times than the larger Aft fibers found in abundance in the gingiva and other soft tissue. Consequently, dental 'short-latency' peaks may occur after 50 msec and be indistinguishable from, or overlapping with, later peaks. In contrast, the distinct gingival wave form obtained prior to 50 msec may reflect the activation of the faster and more numerous Aft afferents rather than the concomitant slower A6 (or perhaps C fiber) volley. If this is the case, then soft tissue waves prior to 50 msec would not be indicators of nociception. Thus, it is likely that subjects undergoing painful gingival stimulation may experience and report pain on each trial, but yield shortlatency EP data that reflect activation of large non-nociceptive fibers at the site of stimulation. In this case, pain would appear to be causally related to the EP data, but, in fact, pain report and short-latency EPs would be two independent phenomena that happen to coincide in time. A second hypothesis, not mutually exclusive of the first, is that tooth pulp afferentation is represented differently than gingival in the central nervous system. This is not readily apparent in the mapping studies of Penfield and Rasmussen (1950), but in such work patients are often inexact in their descriptions of sensations. Moreover, their technique using stimulation of cortex with electrical currents may not correspond exactly to activation of cortex via stimulation of sensory end organs. Work on magnetic potentials, corresponding to tooth pulp stimulation by Hari et al. (1983), indicates that the dental potential originates at the anterior end of the secondary somatosensory cortex rather than primary sensory cortex. Thus, its representation appears to be more primitive and dif-
SHORT-LATENCY EPs ELICITED BY PAINFUL STIMULATION fuse than that of the gingival stimulus. This w o u l d c o r r e s p o n d well with the hypothesis that p a i n t r a n s m i t t i n g areas are distinct from n o r m a l s o m a t o s e n s o r y ones. F u r t h e r m o r e , the o r i e n t a t i o n of the cortically g e n e r a t e d d i p o l e associated with d e n t a l s t i m u l a t i o n m a y b e different than that associated with gingival stimulation~ and F3-P3 or F 4 - P 4 r e c o r d i n g sites m a y be u n f a v o r a b l e for detecting the dental dipole. O u r d a t a d o n o t allow us to d e t e r m i n e w h e t h e r either, or both, of these h y p o t h e s e s m a y be true. F u r t h e r i n q u i r y is w a r r a n t e d in o r d e r to d e t e r m i n e w h e t h e r a s h o r t - l a t e n c y d e n t a l wave form can be d e m o n s t r a t e d with o t h e r electrode p l a c e m e n t s a n d / o r a longer r e c o r d i n g window. Nonetheless, o u r findings suggest that there m a y be significant differences in the n e u r o p h y s i o l o g i c a l processes und e r l y i n g d e n t a l a n d soft tissue s t i m u l a t i o n in p a i n research.
Resume
Comparaison des potentiels bvoqubs trigbminaux courte latence produits par stimulation dentaire ou gingivale douloureuse U n e s t i m u l a t i o n d o u l o u r e u s e de la p u l p e dentaire et de la gencive a 6t6 p r a t i q u e e sur 16 sujets volontaires. Des p o t e n t i e l s 6voques ~t courte latence (15 ~t 50 msec) ont ete enregistres p o u r un total de 800 essais et d a n s c h a q u e cas, ~t F3-P3 ou F4-P4; la c o m p a r a i s o n des o n d e s moyenn6es a 6te effectuee. Le p o t e n t i e l ~ la s t i m u l a t i o n gingivale a 6te clair chez tous les sujets et un m o y e n n a g e entre sujets a p u etre effectue. A l'oppos6, les potentiels la s t i m u l a t i o n d e n t a i r e ne se d i s t i n g u a i e n t pas du bruit ou 6taient d ' u n e g r a n d e instabilit6 d ' u n sujet ~t l'autre. U n rdsultat i n i n t e r p r e t a b l e a ete d o n n e p a r le m o y e n n a g e des o n d e s ~. la s t i m u l a t i o n dentaire de t o u s l e s sujets. I1 est a p p a r u c l a i r e m e n t que les potentiels ~voques d e n t a i r e s ne p o u v a i e n t etre enregistres au niveau de ces sites. Ces rdsultats p e u v e n t 6tre expliques p a r l'une ou p a r les deux h y p o t h e s e s suivantes: (1) les afferences d e n t a i r e s sont en m a j o r i t e d e petites fibres, avec terminaisons nociceptives qui c o n d u i s e n t plus l e n t e m e n t que les affdrences des tissus mous, alors que la
25
s t i m u l a t i o n gingivale active h la lois des p o p u l a tions de petites et de grosses fibres; et (2) la r e p r e s e n t a t i o n d e n t a i r e d a n s le cortex s o m a t o s e n soriel est differente et p h y l o g e n e t i q u e m e n t plus p r i m i t i v e que celle des tissus m o u s avoisinants. Ainsi, la localisation des sites gOnerateurs d a n s le cortex et l ' o r i e n t a t i o n du d i p e l e p o u r r a i e n t ¢~tre d i f f e r e n t s p o u r les p o t e n t i e l s d e n t a i r e s ou gingivaux. The authors would like to thank Merrill McSpadden for his technical assistance in completing this work.
References Badr~ G.O., Hanner, P. and Edstrom, S. Cortical evoked potentials in response to trigeminal nerve stimulations in humans. Clin. Electroenceph., 1983, 34: 61-66. Benedetti, C., Chapman, C.R., Colpitts, Y.H. and Chen, A.C. Effect of nitrous oxide concentration on event-related potentials during painful tooth stimulation. Anestbesiology, 1982, 56: 360-364. Bennett, M.H. and Jannetta, P.J. Trigeminal evoked potentials in humans. Electroenceph. clin. Neurophysiol., 1980, 48: 517-526. Beyers, M. Dental sensory receptors. Int. Rev. Neurobiol., 1984, 25: 39-94. Bromm, B. and Scharein, E. Principal component analysis of pain-related cerebral potentials to mechanical and electrical stimulation in man. Electroenceph. clin. Neurophysiol., 1982, 53: 94-103. Buchsbaum, M.S.. Davis, G.C., Goodwin, F.K., Murphy, D.L, and Post, R.M. Psychophysical pain judgments and somatosensory evoked potentials in patients with affective illness and in normal adults. In: C. Perris, L. von Knorring and D. Kemali (Eds.), Clinical Neurophysiological Aspects of Psychopathological Conditions. Karger, Basel. 1980: 63-72. Buchsbaum, M.S., Davis, G.C., Coppola, R. and Naber, D, Opiate pharmacology and individual differences. It, Somatosensory evoked potentials. Pain, 1981, 10: 367-377. Buettner, U.W., Petruch, F., Scheglmann, K. and StCShr, M. Diagnostic significance of cortical somatosensory evoked potential following trigeminal nerve stimulation. In: J. Courjon, F. Mauguihre and M. Revol (Eds.), Advances in Neurology. Raven Press, New York, 1982: 339-345. Butler, S.H., Colpitts, Y.H., Gagliardi, O.J., Chen, A.C,N. and Chapman, C.R. Opiate analgesia and its antagonism in dental event-related potentials: evidence for pl~icebo antagonism. Psychopharmacology, 1983, 79:325 328. Carmon, A., Dotan, Y. and Same, Y, Correlation of subjective pain experience with cerebral evoked response to noxious thermal stimulation. Exp. Brain Res. 1978, 33: 445-453.
26 Chapman, C.R. and Benedetti, C. Nitrous oxide effects on cerebral evoked potential: partial reversal with a narcotic antagonist. Anesthesiology, 1979, 51: 135-138. Chapman, C.R., Colpitts, Y.M., Benedetti, C., Kitaeff, R. and Gehrig, J.D. Evoked potential assessment of acupunctural analgesia: attempted reversal with naloxone. Pain, 1980, 9: 183 197. Chatrian, G.E., Canfield, R.C., Knauss, T.A. and Lettich, E. Cerebral responses to electrical tooth pulp stimulation in man. An objective correlate of acute experimental pain. Neurology (Minneap.), 1975, 25: 745-757. Chen, A.C.N., Chapman, C.R. and Harkins, S.W. Brain evoked potentials are functional correlates of induced pain in man. Pain. 1979, 6: 365-374. Chudler. E.H. and Dong, W.K. The assessment of pain by cerebral evoked potentials. Pain, 1983, 16:221 244. Drechsler, F. Short and long latency cortical potentials following trigeminal nerve stimulation in man. In: C. Barber (Ed.), Evoked Potentials. University Park Press, Baltimore, MD, 1980: 415-422. Gehrig, J.D., Colpitts, Y.H. and Chapman, C.R. Effects of local anesthetic infiltration on brain potentials evoked by painful dental stimulation. Anesth. Analg., 1981, 60: 779-782. Hari, R., Kaukoranta, E., Reinikainen, K., Huopaniemi, T. and Mauno, J. Neuromagnetic localization of cortical activity evoked by painful dental stimulation in man. Neurosci. Lett., 1983, 42: 77-82. Harkins, S.W. and Chapman, C.R. Cerebral evoked potentials to noxious dental stimulation: relationship to subjective pain report. Psychophysiology, 1978, 15: 248-252. Martin, R.W. and Chapman, C.R. Dental dolorimetry for human pain research: methods and apparatus. Pain, 1979, 6: 349-364.
C.R. CHAPMAN ET AL. Mumford, J.D. and Bowsher, D. Pain and protopathic sensibility. A review with particular reference to the teeth. Pain, 1976, 2: 223-243. Penfield, W. and Rasmussen, T. The Cerebral Cortex of Man. Macmillan Press, New York, 1950. Salar, G., Iob, I. and Mingrino, S. Somatosensory evoked potentials before and after percutaneous thermal coagulation of the gasserian ganglion for trigeminal neuralgia. In: J. Courjon, F. MauguiOre and M. Revol (Eds.), Advances in Neurology. Vol. 32. Clinical Applications of Evoked Potentials in Neurology. Raven Press, New York, 1982:359 365. Sano, H. Influence of intensity-varied electrical stimulation of a tooth and 30% N20 premixed gas inhalation on somatosensory evoked potentials (SEPs). Jap. J. Dent. Anesth., 1977, 5: 9-21. Schimek, R., Chapman, C.R., Gerlach, R. and Colpitts, Y.H. Varying electrical acupuncture stimulation intensity: effects on dental pain evoked potentials. Anesth. Analg. (Cleveland), 1982, 61: 499-503. Singh, N., Sachdev, K.K. and Brisman, R. Trigeminal nerve stimulation: short latency somatosensory evoked potentials. Neurology (NY), 1982, 32: 97-101. StOhr, M. and Petruch, F. Somatosensory evoked potentials following stimulation of trigeminal nerve in man. J. Neurol., 1979, 220: 95-98. StOhr, M.. Petruch, F. and Scheglmann, K. Somatosensory evoked potentials following trigeminal nerve stimulation in trigeminal neuralgia. Ann. Neurol., 1981, 9: 63-66. Stowell, H. Cerebral slow waves related to the perception of pain in man. Brain Res. Bull., 1977. 2: 23-30.
Electroencephalograpt~v and clinical Neurophysiologv, 1986, 65: 20-26 Elsevier Scientific Publishers Ireland, Ltd.
C O M P A R I S O N O F S H O R T - L A T E N C Y T R I G E M I N A L EVOKED P O T E N T I A L S ELICITED BY PAINFUL DENTAL AND GINGIVAL S T I M U L A T I O N 1 C. R I C H A R D C H A P M A N , REBECCA G E R L A C H , R O B E R T JACOBSON, V E R O N I C A B U F F I N G T O N and ELIEZAR KAUFMANN
Department o[ Anesthesiologo'. University of Washington School of Medicine, Seattle, WA 98195 (U.S.A.) (Accepted for publication: July 1, 1985)
Summary
Painful stimulation of tooth pulp and of the maxillary gingiva was undertaken in 16 volunteers. Short-latency evoked potentials (15-50 msec) were recorded over 800 trials in each case at F3-P3 of F4-P4, and the resultant averaged wave forms were compared. The gingival wave was distinct in all subjects and could be averaged across subjects while the dental waves were either noise or very inconsistent over subjects. Averaging of the dental wave forms across subjects yielded an uninterpretable result. It was clear that dental evoked potentials could not be recorded at these sites. These findings could be explained by either or both of two hypotheses: (1) dental afferents are predominantly small fiber, nociceptive end organs that conduct more slowly than soft tissue afferents whereas gingival stimulation activates both large and small fiber populations; and (2) dental representation in somatosensory cortex is different and phylogenetically more primitive than that of neighboring soft tissue. Therefore, the location of the generator sites in cortex and the orientation of the dipole may be different for dental than for gingival wave forms. Keywords: dental stimulation - trigeminal evoked potentials - gingival stimulation
Evoked potentials (EPs) are attracting increasing attention as possible correlates of experimental pain in man and many investigators have used painful stimulation of the face or oral cavity in such research (reviewed by Chudler and Dong 1983). Most investigations have targeted longlatency wave forms which occur between 50 and 500 msec. The amplitudes of such waves have been reported to correlate with stimulus intensity and subjective reports of pain (Chatrian et al. 1975; Sano 1977; Stowell 1977; Carmon et al. 1978; Harkins and Chapman 1978; Chen et al. 1979; Buchsbaum et al. 1980). In addition, long-latency wave form amplitudes decrease with subjective pain report when an analgesic intervention is given (Chapman and Benedetti 1979; Chapman et al. 1980; Buchsbaum et al. 1981; Gehrig et al. 1981; Schimek et al. 1982; Butler et al. 1983) and doseresponse effects have been demonstrated (Benedetti et al. 1982). Short-latency trigeminal waves occurring 15-50 msec following the stimulus have been studied less I This work has been done with the support of N I D R Program Project DE 05130 and N I N C D S Program Project NS 16329.
pain
extensively in pain research than have later peaks, although there are many reports of short-latency EPs elicited by non-painful electrical or mechanical stimulation of face or mucous membrane. EPs to somatosensory stimulation may prove to be of value in the clinical assessment of neural function in patients since the peak latencies of such wave forms vary with the locus of stimulation and the conduction velocity of peripheral and central neural pathways. Short-latency clinical EP studies have most often been done to evaluate patients with orofacial pain (Bennett and Jannetta 1980; St~3hr et al. 1981; Buettner et al. 1982; Salar et al. 1982). Although peak polarities and latencies may vary across studies as a function of recording electrode placement, these studies show that a characteristic triphasic wave form with peaks at roughly 20, 35 and 45 msec can be observed during electrical stimulation of soft tissue in the face or mouth. Dental short-latency potentials in humans have not been previously reported. Dental pulp afferent innervation is predominantly (though not entirely) from relatively slow conducting, unmyelinated C and small, myelinated A6 fibers. While these fibers appear to serve primarily a nociceptive function,
0168-5597/86/$03.50 © 1986 Elsevier Scientific Publishers Ireland, Ltd.
SHORT-LATENCY EPs ELICITED BY PAINFUL STIMULATION
they are also known to subserve other sensory modalities (Mumford and Bowsher 1976; Byers in press). In addition to nociceptors, dental pulp contains Aft parent axons and sympathetic fibers. The tooth pulp is therefore a predominant, but not a pure nociceptive end organ. On the other hand, the soft tissue of the gingiva contains a large number of relatively fast conducting non-nociceptive A/~ fibers in addition to A6 and C fibers and is therefore only partly nociceptive. Consequently, short-latency potentials elicited by painful dental stimulation should differ from those elicited by painful gingival stimulation if the tooth pulp afferent fiber volley is primarily nociceptive. The cortical short-latency dental wave form should either: (1) show later peak latency than the soft tissue EP due to predominance of slow-conducting fibers; or (2) be less distinct than soft tissue when measured at scalp locations over primary and secondary somatosensory cortex due to differences in cortical representation. The following report compares trigeminal short-latency EPs elicited by painful dental stimulation with those elicited by painful gingival stimulation.
Methods
Subjects Sixteen male and female volunteers (10 men and 6 women) between 21 and 40 years of age served as paid volunteers. All were in good health and free of oral pathology. Each read and signed an informed consent statement approved by the University of Washington Human Subjects Institutional Review Board.
Methods Subjects were seated in a dental chair inside a sound attenuated, electrically shielded chamber. They were monitored by the research technologist through a television and two-way microphone circuit. A variable period of practice was undertaken with each subject to acquaint him or her with the equipment, the sensations of stimulation, and assure good control over location of electrode position. Subjects were tested under two conditions: stimulation of a central incisor and stimulation of
21
the maxillary gingiva approximately 1 cm lateral to midline. Stimulation was on the same side in both cases, and the order of the stimulation modalities was counterbalanced across subjects. During the practice period, subjects were required to identify subjectively equal stimulus intensities at dental and gingival sites. There were 800 trials for each stimulus modality. EPs were elicited by repetitive electrical stimulation delivered through a probe that the subject held in place at tooth or gingiva. A stimulator with stimulus isolation and constant current units was used to deliver the electrical stimuli at 150 V at the rate of 1 pulse/2 sec. Dental stimuli were delivered through a 5 mm diameter cylinder of conductive rubber mounted in the hand-held probe. The cathode was held at the edge of a central incisor (Martin and Chapman 1979) and the anode was a Beckman electrode filled with conductive gel that was taped to the skin 0.5 cm lateral to the ala of the nose ipsilateral to the cathode. Gingival stimuli were delivered through 2 metal alloy balls, 1 mm in diameter each, spaced 2 mm apart and mounted in the tip of the hand-held probe. Pulse width was 0.1 msec for gingival stimulation and 2 msec for dental stimuli. Care was taken to avoid contraction of lip or other facial muscles during gingival stimulation. The intraoral electrode was separated from the lip by a cotton dental roll. Subjects were instructed to alert the experimenter to any sensations of muscle contraction. In both cases stimuli were delivered at an intensity that the subject felt to be distinctly but not distressingly painful. For dental stimuli the mean intensity for all subjects was 55 ~A while for gingival stimuli it was 8.60 mA. The sensitivity of the tooth pulp to electrical stimulation is always much greater than that of soft tissue because current density is high in the pulpal chamber. Stimulation was computer controlled.
EP recording Silver recording electrodes were affixed to the scalp with collodion and resistances were kept at or below 5 kI2. Recordings were obtained at either F3-P3 or F4-P4 contralateral to the stimulus with a ground attached to the left zygomatic promi-
22
C.R. CHAPMAN ET AL.
nence. Each sample consisted of 20 msec of base-
~m
l i n e a n d 50 m s e c o f p o s t s t i m u l u s E E G . S i g n a l s were amplified via amplifiers with an effective bandwidth of 0.01-3 kHz. The sampling rate was 7K. The amplified signals were fed into a MINC
,
Lm
/
~m
I. IlI
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Fig. 2. TEP wave forms for 3 subjects shown in Fig. 1. Four successive 200 trial averages elicited by gingival stimulation are shown in the left panel and by dental stimulation in the right panel.
E2P2BB LImI
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~,,,,,~ll~Jnn~.,,,,
italt
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Fig. ]. TEP wave forms for 3 typical subjects. Wave form D is elicited by dental stimulation and wave form G by gingival
stimulation.
Fig. 3. a and b: mean dental (a) and gingival (b) wave forms averaged across subjects plus and minus one standard error at the mean.
SHORT-LATENCY EPs ELICITED BY PAINFUL STIMULATION
LSI 11,/23 computer system that provided A / D conversion, and single-trial wave forms were stored on disk and dumped to tape via a Cipher digital tape drive for later off-line analysis. Averages were obtained off-line and hard copy was obtained with a plotter.
Results The EP wave forms for 3 typical subjects in the gingival and dental stimulation conditions are shown in Fig. 1. The two types of waves are superimposed for each of the subjects. Habituation effects over trials were examined for a subsample of subjects. Within subjects stability in these records can be seen in Fig. 2 where plots of 200 trials each are superimposed for each type of stimulus for each of the 3 subjects. When compared across subjects, the gingival wave forms were distinct and consistent in morphology, while dental waves were either absent, indistinct or idiosyncratic with little similarity over individual volunteers. When clearly defined, the dental waves tend to be smaller in amplitude than gingival waves with markedly different peak latency. This can be seen most clearly when the two types of wave forms are averaged across subjects. Fig. 3a and b display the mean (a) gingival, and (b) dental, wave forms averaged across subjects, plus and minus 1 standard error of the mean. The mean gingival wave form demonstrated clearly definable peaks that are consistent with the reports of Bennett and Jannetta (1980) and others. In
Fig. 4. Mean dental TEP (solid line) and mean gingival TEP (dashed line) with 95% confidence interval.
23
contrast, the mean dental wave was smaller and barely distinguishable from noise. In addition, the figures show that from roughly 15 to 40 msec the between-subjects variability of the data was somewhat greater in the dental than in the gingival stimulation condition. In Fig. 4 the mean dental wave form is shown with a 95% confidence interval. The gingival wave form (dashed line) is superimposed upon it. It can be seen that the major peaks of the gingival wave differ significantly from the dental data since they lie outside the 95% confidence interval.
Discussion Short-latency EPs elicited by gingival stimulation were clearly defined and consistent with the results of other investigations that have attempted to characterize the short-latency trigeminal wave form associated with soft tissue stimulation in normals. Badr et al. (1983) studied 18 normal volunteers, applying electrodes to the corner of the mouth for stimulation. Recording from a point above somatosensory cortex referred to ear lobe, they reported waves characterized as P20, N30, P40 and N50 with N30 being the most consistent feature. StOhr and Petruch (1979) stimulated 55 normal volunteers on the lip using non-painful electrical stimulation while recording from C5 and C6 with Fz as reference. They reported waves characterized as N13, P19 and N26, with P19 being most prominent. Our observations are also consistent with clinical studies of pain patients. Most have employed painless oral or facial somatosensory stimuli. Singh et al. (1982) stimulated the mental nerve at the mandibular foramen and compared EPs in 7 normals with those seen in 25 patients having chronic facial pain or neurologic abnormalities, recording from P3 or P4 referred to clavicle or mastoid. They observed peaks at P23 and N34, with some abnormalities in patients having cranial nerve palsy or acoustic neuromas. Drechsler (1980) also stimulated mental foramen electrically, recording at F3-C3 or F4-C4. The mean wave form for 20 subjects was characterized by P23, N34 and P44 peaks. Buettner et al. (1982) followed the investi-
24
gation noted above by studying EPs elicited by non-painful electrical lip stimulation in tic douloureux patients and reported that P19 latency differed significantly between the normal and affected sides of the face, being later on the involved side. St6hr et al. (1981) examined EPs elicited by lip stimulation in subjects with tic douloureux and found that 41% of 17 patients without prior surgery demonstrated an increased latency for N19 on the involved side. Salar et al. (1982) employed cutaneous electrical stimuli with needle electrodes in trigeminal neuralgia patients before and after percutaneous coagulation of the gasserian ganglion, recording at a point 7 cm from vertex on the vertex-meatus line. They observed a triphasic wave, P20, N35 and P50. EPs varied across patients with reports of sensory loss following surgery, but they did not change as a function of clinical pain. Only Bennett and Jannetta (1980) have used painful stimuli. They electrically stimulated the maxillary gingiva at painful levels on the asymptomatic side in trigeminal neuralgia patients as well as in norreals and sludied the short-latency wave elicited. Scalp recording was done contralateral to the stimulus at the midpoint of a line connecting the auditory meatus and a point 1 cm posterior to vertex with reference to earlobe. The EPs consisted of a triphasic wave form, N20, P34, and N51. These studies show moderately good agreement with one another and with our observations in characterizing the short-latency trigeminal EP elicited by soft tissue stimulation. Only Bennett and Jannetta used painful stimulation. Since their EPs were highly similar to those reported by Badr et al. (1983); Salar et al. (1982), and others mentioned above, their outcomes suggest that pain-related short-latency gingival waves are not different than other somatosensory wave forms elicited from oral soft tissue. Salar et al. (1982) have offered consistent data since their patients showed no differences in short-latency waves as a function of pain sensibility. It is clear from our observations that painful stimulation of tooth pulp and gingival tissue yield different outcomes. Unlike the gingival wave, the amplitude of the dental wave is small when averaged across subjects. As noted above, this result is due to absent, indistinct or idiosyncratic responses
C.R. C H A P M A N ET AL.
for individual subjects and is not a function of averaging distinct large amplitude early wave forms that vary only in latency across subjects. Two hypotheses can be offered to explain this observation. First, the failure of the dental stimulus to elicit a clearly defined wave form within 50 msec may reflect the conduction times of the specific population of sensory end organs stimulated in the tooth pulp. It is probable that dental stimulation at submaximal intensities activates mainly A6 rather than C fibers since the sensations elicited are discrete and not slow or lingering. These fibers have slower conduction times than the larger Aft fibers found in abundance in the gingiva and other soft tissue. Consequently, dental 'short-latency' peaks may occur after 50 msec and be indistinguishable from, or overlapping with, later peaks. In contrast, the distinct gingival wave form obtained prior to 50 msec may reflect the activation of the faster and more numerous Aft afferents rather than the concomitant slower A6 (or perhaps C fiber) volley. If this is the case, then soft tissue waves prior to 50 msec would not be indicators of nociception. Thus, it is likely that subjects undergoing painful gingival stimulation may experience and report pain on each trial, but yield shortlatency EP data that reflect activation of large non-nociceptive fibers at the site of stimulation. In this case, pain would appear to be causally related to the EP data, but, in fact, pain report and short-latency EPs would be two independent phenomena that happen to coincide in time. A second hypothesis, not mutually exclusive of the first, is that tooth pulp afferentation is represented differently than gingival in the central nervous system. This is not readily apparent in the mapping studies of Penfield and Rasmussen (1950), but in such work patients are often inexact in their descriptions of sensations. Moreover, their technique using stimulation of cortex with electrical currents may not correspond exactly to activation of cortex via stimulation of sensory end organs. Work on magnetic potentials, corresponding to tooth pulp stimulation by Hari et al. (1983), indicates that the dental potential originates at the anterior end of the secondary somatosensory cortex rather than primary sensory cortex. Thus, its representation appears to be more primitive and dif-
SHORT-LATENCY EPs ELICITED BY PAINFUL STIMULATION fuse than that of the gingival stimulus. This w o u l d c o r r e s p o n d well with the hypothesis that p a i n t r a n s m i t t i n g areas are distinct from n o r m a l s o m a t o s e n s o r y ones. F u r t h e r m o r e , the o r i e n t a t i o n of the cortically g e n e r a t e d d i p o l e associated with d e n t a l s t i m u l a t i o n m a y b e different than that associated with gingival stimulation~ and F3-P3 or F 4 - P 4 r e c o r d i n g sites m a y be u n f a v o r a b l e for detecting the dental dipole. O u r d a t a d o n o t allow us to d e t e r m i n e w h e t h e r either, or both, of these h y p o t h e s e s m a y be true. F u r t h e r i n q u i r y is w a r r a n t e d in o r d e r to d e t e r m i n e w h e t h e r a s h o r t - l a t e n c y d e n t a l wave form can be d e m o n s t r a t e d with o t h e r electrode p l a c e m e n t s a n d / o r a longer r e c o r d i n g window. Nonetheless, o u r findings suggest that there m a y be significant differences in the n e u r o p h y s i o l o g i c a l processes und e r l y i n g d e n t a l a n d soft tissue s t i m u l a t i o n in p a i n research.
Resume
Comparaison des potentiels bvoqubs trigbminaux courte latence produits par stimulation dentaire ou gingivale douloureuse U n e s t i m u l a t i o n d o u l o u r e u s e de la p u l p e dentaire et de la gencive a 6t6 p r a t i q u e e sur 16 sujets volontaires. Des p o t e n t i e l s 6voques ~t courte latence (15 ~t 50 msec) ont ete enregistres p o u r un total de 800 essais et d a n s c h a q u e cas, ~t F3-P3 ou F4-P4; la c o m p a r a i s o n des o n d e s moyenn6es a 6te effectuee. Le p o t e n t i e l ~ la s t i m u l a t i o n gingivale a 6te clair chez tous les sujets et un m o y e n n a g e entre sujets a p u etre effectue. A l'oppos6, les potentiels la s t i m u l a t i o n d e n t a i r e ne se d i s t i n g u a i e n t pas du bruit ou 6taient d ' u n e g r a n d e instabilit6 d ' u n sujet ~t l'autre. U n rdsultat i n i n t e r p r e t a b l e a ete d o n n e p a r le m o y e n n a g e des o n d e s ~. la s t i m u l a t i o n dentaire de t o u s l e s sujets. I1 est a p p a r u c l a i r e m e n t que les potentiels ~voques d e n t a i r e s ne p o u v a i e n t etre enregistres au niveau de ces sites. Ces rdsultats p e u v e n t 6tre expliques p a r l'une ou p a r les deux h y p o t h e s e s suivantes: (1) les afferences d e n t a i r e s sont en m a j o r i t e d e petites fibres, avec terminaisons nociceptives qui c o n d u i s e n t plus l e n t e m e n t que les affdrences des tissus mous, alors que la
25
s t i m u l a t i o n gingivale active h la lois des p o p u l a tions de petites et de grosses fibres; et (2) la r e p r e s e n t a t i o n d e n t a i r e d a n s le cortex s o m a t o s e n soriel est differente et p h y l o g e n e t i q u e m e n t plus p r i m i t i v e que celle des tissus m o u s avoisinants. Ainsi, la localisation des sites gOnerateurs d a n s le cortex et l ' o r i e n t a t i o n du d i p e l e p o u r r a i e n t ¢~tre d i f f e r e n t s p o u r les p o t e n t i e l s d e n t a i r e s ou gingivaux. The authors would like to thank Merrill McSpadden for his technical assistance in completing this work.
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