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Inhibition of jaw-closing muscles by electrical stimulation of the ophthalmic division in man
298
Brain Research, 371 (1986) 298-304 Elsevier
BRE 11624
Inhibition of Jaw-Closing Muscles by Electrical Stimulation of the Ophthalmic Division in Man G. CRUCCU 1,, R. AGOSTINO1, J. LAHUERTA2 and M. MANFREDI 1 tDipartimento di Scienze Neurologiche, Universita' di Roma 'La Sapienza', Rome (Italy) and 2pain Relief Foundation and Department of Neurosciences, Walton Hospital, Liverpool (U. K.) (Accepted August 27th, 1985) Key words: trigeminal nerve - - masticatory muscle - - electromyography - - silent period - - blink reflex
High-intensity stimulation of the supraorbital region elicits, together with a blink reflex, a reflex inhibition of the jaw-closing muscles in normal man. The response differs from the well known inhibition obtained by intra- and perioral stimulation in two main features. Firstly, it consists of a single late silent period (SP), only occasionally preceded by a short and partial decrease of the background EMG activity: secondly, the inhibitory response appears at a rather high threshold, requiring a stimulus intensity which is 4-fold the sensory perception threshold and 3-fold that required to evoke the blink reflex. Electrical and mechanical stimulation of the cornea failed to evoke a significant inhibitory reflex. The silent period and the blink reflex were similarly affected by local anaesthetic infiltration of the supraorbital skin, suggesting that the afferents subserving the two reflexes belong to the same fibre group; the higher threshold of the supraorbital inhibitory response may be explained by the need for a larger spatial summation. The considerable latency gain and relatively rapid habituation shown by the supraorbital inhibitory response imply a multisynaptic circuit, similar to that responsible for the second silent period which occurs following 'oral' stimulation. A common interneuronalnet for these two reflexes is suggested by the results of interaction experiments employing combined supra- and infraorbital stimulation. INTRODUCTION The most evident effect of mechanical stimulation in the territory of the first trigeminal division in man is the bilateral contraction of the orbicularis oculi muscles. Electrophysiological recordings show that electrical stimulation of the supraorbital nerve evokes early and late excitatory responses in these muscles, respectively known as the R1 and R2 components of the blink reflex 12A4. Mechanical or electrical stimulation of the corneal mucosa evokes a late response (corneal reflex) similar to R21,19, but with longer latency and duration 2,21. R1 is supposed to be mediated by oligosynaptic i n t e r n e u r o n a l relays in the pons, while R2 and the corneal reflex are mediated by polysynaptic b u l b o p o n t i n e circuits 13,2529. Although less consistently obtained, a supraorbital-abducens reflex 3 and a corneopterygoid reflex 22 have also been reported. This paper describes an inhibitory reflex recorded from the masseter and temporal muscles following
electrical stimulation of the supraorbital region in normal subjects. This reflex shows features which are different from the inhibition commonly exerted by intra- and perioral sensory stimulationl°,tlA6: it is evoked only by high-intensity noxious stimuli and it usually consists of a late single silent period (SP), with similar features and possibly the same central circuits of the second silent period which follows 'oral' stimulation. MATERIALS AND METHODS Experiments were carried out in 11 normal volunteers (25-40 years) of either sex, after informed consent was granted. The experiments were conducted while subjects sat on a dentist chair with a head-rest. Single squarewave negative pulses (0.1-0.5 ms, 10-70 m A ) were delivered through a pair of surface electrodes to the skin overlying the supraorbital nerve close to the supraorbital notch. The corneal mucosa was stimulated
Correspondence: M. Manfredi, Dipartimento di Scienze Neurologiche, Universita' di Roma, Viale Universita', 30, 00185 Roma, Italy, 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)
299 either mechanically, with a metal sphere (2 mm diameter) connected to the trigger circuit 24 or electrically, by means of a fine cotton thread emerging from a glass pipette filled with saline-soaked gauze and connected to the cathode of the stimulator; the anode was connected to the earlobeL Single square-wave pulses (1 ms, 80-2000~A) were used. E M G activity was recorded by surface electrodes or non-insulated needles from masseter, temporal and orbicularis oculi muscles on both sides. Signals were amplified (band width 20-5000 Hz), full waverectified, averaged and stored on floppy disks (Biopotential Analyzer Software Interactive System, OTE). Subjects were asked to clench their teeth in order to produce maximal E M G activity and to maintain it for periods of 1 s, with the aid of visual and auditory feed-back. The contractions were serially repeated after 10-30 s of rest; the E M G signals were averaged to provide a background level of E M G activity. Provided that stimuli of adequate intensity were delivered, 8-32 averaged trials were sufficient to yield good visualization and accurate measurements of the silent period (SP). Latencies and duration of SPs w e r e measured at the point of crossing between the inhibitory shift and a baseline indicating 80% of the background level of E M G activity (Fig. 4). SPs' areas were automatically computed and expressed both as absolute arbitrary units (AUs) and as percentage of background EMG. The reflex threshold was defined as the lowest stimulus intensity evoking, in single trials, pauses of electrical silence (independently from their duration) within the latency range of the SP and, in the averaged signal, a 50% suppression of the background EMG. Five subjects underwent local anaesthetic block of the supraorbital nerve. Supramaximal stimuli were delivered through a pair of fine insulated needles with a 3 mm bare tip inserted subcutaneously 15 mm apart along the course of the nerve. Prior to the block, signals were recorded from the ipsilateral masseter and orbicularis oculi muscle and averaged (16 trials), thus providing a baseline for SP and the blink reflex. Immediately afterwards, 1.5-2 ml of 1% lignocaine were injected around the stimulating electrodes. Stimulation and recording procedures were unchanged. Following the injection, recordings were repeated every 4 min until the complete disappearance of the reflex responses.
Conditioning experiments with the double shock technique were performed in 4 subjects. Supramaximal paired stimuli (100 ms interval) were delivered to the supraorbital nerve. This interstimulus interval was chosen because it yielded the best differential effect on the 'oral' early and late silent periods without overlapping of responses to first and second shockX The trial was repeated 16 times. The area and duration of the averaged test response (second shock) were compared with the unconditioned response's (first shock). In order to study the interaction between the two afferent volleys, the same procedure was repeated after 15 min by delivering the first shock to the supraorbital nerve and the second one to the ipsilateral infraorbital nerve; after a further 15 min the sequence of shocks was reversed. Statistical significance was evaluated with the Student's t-test.
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Fig. 1. Responses of facial muscles to supraorbital nerve stimulation: (A) at rest; and (B) during contraction of jaw-closing muscles. Recordings from ipsilateral orbicularis oculi (1), temporal (2) and masseter (3) muscles. Averages of 16 rectified responses. Sweep 200 ms; sensitivity 200 ktV.
300 RESULTS Responses to stimulation o f the ophthalmic division Fig. 1 shows the effect of supraorbital stimulation on the orbicularis oculi, temporal and masseter muscles. At rest, excitatory responses could be evoked only in the orbicularis oculi muscle (Fig. 1A). When the subject clenched his teeth (Fig. 1B), an inhibitory response in the masticatory muscles became evident in 10 out of 11 cases. The inhibition took place between 35 and 75 ms after supraorbital stimulation. No significant differences between temporalis and masseter or between ipsi- and contralateral homonimous muscles were observed (Table I). The threshold for the SP was 4.2 times the sensory threshold and 3.4 times the threshold for R2. SP threshold stimuli were always reported as painful and rated 3 - 4 in an arbitrary pain scale of 5 steps 7. In half of the subjects supramaximal stimuli also induced an early (10-25 ms) attenuation of background E M G , although never amounting to electric silence. Electrical stimulation of the corneal mucosa evoked a suppression of the background E M G activity in 4 out of 6 subjects. However, the threshold was more than 8 times the sensory threshold or the corneal reflex threshold. The subjects often perceived sensations from the surrounding skin or the earlobe, and occasionally displayed an early E M G activity (Rl-like) in the ipsilateral orbicularis oculi. Mechanical stimuli applied to the corneal mucosa evoked corneal reflexes but failed to induce reproducible pauses in the masseter activity. It was concluded that the SPs observed with electrical stimulation of the cornea were possibly due to stimulus spread.
Silent periods to 'oral' stimulation Fig. 2 shows the responses to stimulation of various structures innervated by the trigeminal nerve and of an extratrigeminal territory. As expected, stimulation of the infraorbital nerve, of the labial mucosa and of the central incisor (Fig. 2 B - D ) at 2 - 3 times the sensory threshold, evoked a double silent period (SP1 and SP2) similar to previously reported 'oral' SPs5,10,16. Supramaximal stimulation of the skin on the lateral aspect of the neck (C3) did not induce any modification in background E M G (Fig. 2E). Table II summarises the features of late SPs following either supraorbital or infraorbital stimulation, the latter being taken as representative of the 'oral' SP2s. The two reflexes were fairly similar, the only remarkable difference between them corresponding to the threshold values, which were significantly lower for the infraorbital-SP (P < 0.01).
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TABLE I Latencies and durations of SPs from ipsi- and contralateral masseter and temporal muscles following supraorbital stimulation Recording (7 subjects) lpsilateral masseter
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Contralateral temporalis
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Fig. 2. Masseter silent periods following stimulation of various trigeminal and extratrigeminal areas. Stimulation of the supraorbital nerve (A), infraorbital nerve (B), lip (C), tooth (D) and the lateral aspect of the neck (E). Recordings from ipsilateral masseter. Superimposition of 4 responses. Sweep 200 ms; sensitivity 500/~V.
301 TABLE II
Comparison between 'oral' SP2 and supraorbital-SP
were still present, although the pain sensation evoked by the stimulus had already disappeared. The amplitude of the reflexes progressively decreased,
Number of subjects with definite responses
Reflex-threshold ( x sensory threshold) Latency (ms) Duration (ms) Area (AUs)
Infraorbital n. (lOoutoflO)
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2.35 + 0.94 43 + 2.67 40 _ 5.8 95.5 + 33
4.17 +_ 1.60 36 + 2.47 38 + 8.2 63.8 + 40
Anaesthetic block Fig. 3 shows the effect of anaesthetic infiltration around the supraorbital nerve on the SP and the blink reflex. Four minutes after the block both reflexes
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together with touch sensation, until their complete disappearance after 12 min. The time course of the block varied in different subjects, but the SP and the blink reflex were always affected in parallel.
Latency gain and habituation By increasing the intensity of the supraorbital nerve stimulation, the latency of SP response became consistently shorter (Fig. 4A). The difference between responses to supramaximal and threshold stimuli (8 ms + 6 S.D.) was statistically significant (P
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Fig. 4. Latency gain and habituation. A: stimulation of the supraorbital nerve at threshold (top trace) and at tolerance (bottom trace) intensity. B: random stimulation at a low rate (top trace) and repetitive 1 Hz stimulation (bottom trace) of the supraorbital nerve. Recordings from ipsilateral masseter. Averages of 16 rectified responses. Sweep 200 ms; sensitivity 200 /tV. A baseline indicating the 80% of background EMG level is superimposed on each trace (arrowheads). Arrows and hatching indicate SP-latencies and SP-areas, respectively.
302 < 0.01). The latencies of R1 and R2 concurrently fell by 0.6 ms and 15 ms respectively, values which correspond to those previously reported2,29. The rate of habituation was investigated by comparing the averaged SP's areas in response to 16 low frequency random stimuli and to 16 repetitive 1 Hz stimuli. During repetitive stimulation (Fig. 4B), the response was reduced by 58% (+ 34 S.D.); the difference was statistically significant (P < 0.001). As expected, R1 was not significantly affected, while R2 completely disappeared after the third or fourth stimulus.
the supraorbital nerve completely abolished the test SP (Fig. 5A). The same sequence delivered to the infraorbital nerve markedly suppressed the test SP2, but left unaffected the test SP1 (Fig. 5B). Similarly, a conditioning infraorbital shock completely suppressed the test supraorbital-SP (Fig. 5D), while a conditioning supraorbital shock only suppressed the infraorbital-SP2 but not SP1 (Fig. 5C). The degree of suppression of the test SP2 varied among subjects, but it is significant that both supra- and infraorbital conditionings were equally effective in the same subject.
Excitability and interaction
DISCUSSION
Fig. 5 shows the results of double shock stimulation. Paired stimuli delivered at a 100 ms interval to
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Stimuli slightly above 4,10 or below 18,2°,3°, the threshold for pain, delivered to the tongue H, teethS, Is, gums a°,3°, lips 1°, infraorbital nerve23, 3°, mental nerve 5,23 or the intracranial portion of the trigeminal nerve 6, evoke a double silent period of the masseter and temporal muscles. The latency shows some variation according to the site of stimulation, but it never exceeds 17 ms 16. Stimulation outside the above-mentioned structures, such as the ophthalmic division or the cranial cervical dermatomes, has been repeatedly reported to be ineffective1°, 30. On the contrary, we have been able to record in 90% of subjects a late silent period from the jaw elevators of both sides following stimulation of the supraorbital nerve. The different results obtained by previous investigators can be explained by the high-stimulus intensities necessary to evoke the response, which were frankly painful to all the subjects tested. Also, the absence or inconsistency of an early inhibition, and the habituation of the late SP, could give the impression of a negative result. The afferents responsible for the supraorbital-SP might belong to the small-myelinated (A6) group, since only noxious stimuli were able to elicit the reflex. However, the anaesthetic block affected the supraorbital-SP to the same extent and with the same time course as the blink reflex. Both components of the blink reflex are supposed to be mediated by cutaneous fibres26, 2s and indirect evidence has been provided that the conduction velocity of the afferents for R16,27 and for R227 falls within the/3 range. The assumption that the afferents subserving the SP were myelinated fibres of intermediate diameter, could be
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Fig. 5. Double shock conditioning. A first (conditioning) shock is delivered to the supraorbital nerve (A, C) or the infraorbital
nerve (B, D). After 100 ms a second (test) shock is delivered to the supraorbital nerve (A, D) or the infraorbital nerve (B, C). Recordings from ipsilateral masseter. Averages of 16 rectified responses. Sweep 200 ms; sensitivity 200 ktV. Arrows indicate timing of first and second shock.
303 indirectly supported by the absence of a significant silent period following corneal stimulation, since the cornea is innervated by small myelinated and unmyelinated (C) fibres onlylS. It is possible that a great number of afferents need to be activated, thus creating a large spatial summation at some synapse, in order to obtain the reflex, which is otherwise absent following a weaker input. The question of the fibre group mediating the SP cannot, therefore, be definitely settled until direct measure of the conduction velocity is obtained. The latency gain exhibited by a reflex when the stimulus intensity increases from threshold to supramaximal level is a function of the number of interneurones in the reflex circuit, owing to spatial summation taking place at each synapse. In the case of the blink reflex, which shares the afferent branch with the SP, the latency gain of R1 (oligosynaptic) is clearly much smaller than that of R2 (polysynaptic) 2,13,2s,29. The supraorbital-SP showed a latency gain of some 8 ms, which is intermediate between those observed for R1 and R2. This would indicate that the SP response is mediated by an intermediate number of interneurones. The same conclusion could be drawn from the effect of repetitive stimulation. The supraorbital-SP habituated more rapidly than R1 but less than the R2 component of the blink reflex. In this regard, however, any direct comparison between an inhibitory and an excitatory reflex is obscured by the fact that the former is recorded during voluntary contraction of the muscle, i.e. a condition wherein motoneurones and interneurones are facilitated by the pyramidal activation 17. The supraorbital-SP shares the efferent branch of the reflex arc with the 'oral' SP1 and SP2. Both latency gain and habituation of supraorbital-
REFERENCES 1 Accornero, N., Berardelli, A., Bini, G., Cruccu, G. and Manfredi, M., Corneal reflex elicited by electrical stimulation of the human cornea, Neurology, 30 (1980) 782-785. 2 Berardelli, A., Cruccu, G., Manfredi, M., Rothwell, J.C.R., Day, B.C. and Marsden, C.D., Corneal reflex and R2 component of the blink reflex, Neurology, 35 (1985) 797-801. 3 Bratzlavsky, M. and Vandeer Eecken, H., Trigemino-abducens reflex in man, Exp. Neurol., 49 (1975) 336-338.
SP were comparable to those reported for the SP2 following lip, tooth and mental nerve stimulationS-10. Furthermore, the recovery after double-shock stimulation shows that the test supraorbital-SP is completely suppressed by a conditioning stimulus delivered 100 ms earlier. The same behaviour is shown by the SP2 to 'oral' stimulation, while SP1 is unaffectedS. These results point at a similar multisynaptic organization for the two late inhibitory reflexes. Finally, interaction experiments showed that a conditioning stimulus delivered to the infraorbital nerve completely abolishes the supraorbital-SP, whereas a conditioning stimulus delivered to the supraorbital nerve suppresses only SP2 but not SP1 to infraorbital stimulation. This confirms a previous hypothesis5,10 which suggested that SP1 and SP2 responses to 'oral' stimuli are mediated by separate neuronal nets and implies that the same interneurons are shared by SP2 and the supraorbital-SP. Findings in patients with brainstem lesions have indicated that the 'oral' SPs are mediated entirely at pons level 23. The same should apply, therefore, to the supraorbital-SP. It is not yet altogether clear whether the 'oral' SPs subserve a defense reaction or a masticatory mechanism. It is even more difficult to understand the functional significance of a reflex inhibition of the masticatory muscles evoked by stimulation of the ophthalmic division. The different characteristics of early and late SPs shown in the present study support the view that they exert different functional roles. ACKNOWLEDGEMENTS This work was supported by a grant from the Consiglio Nazionale delle Ricerche, Roma, PF Medicina preventiva e riabilitativa SP8.
4 Bratzlavsky, M., De Boever, J. and Vandeer Eecken, H., Tooth pulpal reflexes in jaw musculature in man, Arch. Oral. Biol., 21 (1976) 491-493. 5 Cruccu, G., Agostino, R., Fornarelli, M., Inghilleri, M. and Manfredi, M., Recovery cycle of the masseter inhibitory reflex in man, Neurosci. Lett., 49 (1984) 63-68. 6 Cruccu, G. and Bowsher, D., Intracranial stimulation of trigeminal nerve in man. II. Reflex responses, J. Neurol. Neurosurg. Psychiat., 49 (1986). 7 Cruccu, G., Fornarelli, M., Inghilleri, M. and Manfredi, M., The limits of tooth pulp evoked potentials for pain
304 quantitation, Physiol. Behav., 31 (1983) 339-342. 8 Cruccu, G. and Manfredi, M., Masseter inhibitory reflex from stimulation of tooth pulp and mental nerve, Pain, Suppl. 2 (1984) 96. 9 Desmedt, J.E. and Godaux, E., Habituation of exteroceptive suppression and of exteroceptive reflexes in man as influenced by voluntary contraction, Brain Research, 106 (1976) 21-29. 10 Godaux, E. and Desmedt, J.E., Exteroceptive suppression and motor control of the masseter and temporalis muscles in normal man, Brain Research, 85 (1975) 447-458. 11 Hoffmann, P. and Tonnies, J.F., Nachweis des voelligkostanten Vorkommens des Zungen-Kieferreflexes beim Menschen, Pfliigers Arch., 250 (1948) 103-108. 12 Kimura, J., Clinical uses of the electrically elicited blink reflex, Adv. Neurol., 39 (1983)773-786. 13 Kimura, J. and Lyon, L.W., Orbicularis oculi reflex in Wallenberg syndrome: alteration of the late reflex by lesions of the spinal tract and nucleus of the trigeminal nerve, J. Neurol. Neurosurg. Psychiat. , 35 (1972) 228-233. 14 Kugelberg, E., Facial reflexes, Brain, 75 (1952) 385-396. 15 Lele, P.P. and Weddell, G., Sensory nerves of the cornea and cutaneous sensibility, Exp. Neurol., 1 (1959) 334-359. 16 Lund, J.P., Lamarre, Y., Lavigne, G. and Duquet, G., Human jaw reflexes, Adv. Neurol., 39 (1983) 739-755. 17 Lundberg, A. and Voorhoeve, P., Effects from the pyramidal tract on spinal reflex arcs, Acta Physiol. Scand., 56 (1962) 201-219. 18 McGrath, P.A., Sharav, Y., Dubner, R. and Gracely, R.H., Masseter inhibitory periods and sensation evoked by electrical tooth pulp stimulation, Pain, 10 (1981) 1-17. 19 Magladery, J.W. and Teasdall, R.D., Corneal reflexes: an electromyographic study in man, Arch. Neurol., 5 (1961) 269-274. 20 Matthews, B., Mastication. In C. Lavelle (Ed.), Applied Physiology of the Mouth, Wright, Bristol, 1975, pp.
199-242. 21 Ongerboer de Visser, B.W., Comparative study of corneal and blink reflex latencies in patients with segmental or with cerebral lesions, Adv. Neurol., 39 (1983) 757-772. 22 Ongerboer de Visser, B.W. and De Jong, J.M.B.V., The recorded corneomandibular reflex in precentro-bulbar tract lesions, Electroencephalogr. Clin. Neurophysiol., 56 (1983) S148. 23 Ongerboer de Visser, B.W. and Goor, C., Cutaneous silent period in masseter muscles. Electrophysiological and anatomical data, J. Neurol. Neurosurg. Psychiat., 39 (1976) 674-679. 24 Ongerboer de Visser, B.W., Melchelse, K. and Megens, P.H.A., Corneal reflex latency in trigeminal nerve lesions, Neurology, 27 (1977) 1164-1167. 25 Ongerboer de Visser, B.W. and Moffie, D., Effects of brainstem and thalamic lesions on the corneal reflex, Brain, 102 (1979) 595-608. 26 Penders, C.A. and Delwaide, P.J., Physiologic approach to the human blink reflex. In J.E. Desmedt (Ed.), New Devel-
opments in Electromyography and Clinical Neurophysiology, Vol. 3, Karger, Basel, 1973, pp. 641-648. 27 Shahani, B.T., The human blink reflex, J. Neurol. Neurosurg. Psychiat., 33 (1970) 792-800. 28 Shahani, B.T. and Young, R.R., Blink reflexes in orbicularis oculi. In J.E. Desmedt (Ed.), New Developments in
Electromyography and Clinical Neurophysiology, Vol. 3, Karger, Basel, 1973, pp. 641-648. 29 Trontelj, M.A. and Trontelj, J.V., Reflex arc of the first component of the human blink: a single motoneurone study, J. Neurol. Neurosurg. Psychiat., 41 (1978) 538-547. 30 Yu, S.K., Schmitt, A. and Sessle, B.J., Inhibitory effects on jaw muscle activity of innocuous and noxious stimulation of facial and intraoral sites in man, Arch. Oral. Biol., 18 (1973) 861-870.
Brain Research, 371 (1986) 298-304 Elsevier
BRE 11624
Inhibition of Jaw-Closing Muscles by Electrical Stimulation of the Ophthalmic Division in Man G. CRUCCU 1,, R. AGOSTINO1, J. LAHUERTA2 and M. MANFREDI 1 tDipartimento di Scienze Neurologiche, Universita' di Roma 'La Sapienza', Rome (Italy) and 2pain Relief Foundation and Department of Neurosciences, Walton Hospital, Liverpool (U. K.) (Accepted August 27th, 1985) Key words: trigeminal nerve - - masticatory muscle - - electromyography - - silent period - - blink reflex
High-intensity stimulation of the supraorbital region elicits, together with a blink reflex, a reflex inhibition of the jaw-closing muscles in normal man. The response differs from the well known inhibition obtained by intra- and perioral stimulation in two main features. Firstly, it consists of a single late silent period (SP), only occasionally preceded by a short and partial decrease of the background EMG activity: secondly, the inhibitory response appears at a rather high threshold, requiring a stimulus intensity which is 4-fold the sensory perception threshold and 3-fold that required to evoke the blink reflex. Electrical and mechanical stimulation of the cornea failed to evoke a significant inhibitory reflex. The silent period and the blink reflex were similarly affected by local anaesthetic infiltration of the supraorbital skin, suggesting that the afferents subserving the two reflexes belong to the same fibre group; the higher threshold of the supraorbital inhibitory response may be explained by the need for a larger spatial summation. The considerable latency gain and relatively rapid habituation shown by the supraorbital inhibitory response imply a multisynaptic circuit, similar to that responsible for the second silent period which occurs following 'oral' stimulation. A common interneuronalnet for these two reflexes is suggested by the results of interaction experiments employing combined supra- and infraorbital stimulation. INTRODUCTION The most evident effect of mechanical stimulation in the territory of the first trigeminal division in man is the bilateral contraction of the orbicularis oculi muscles. Electrophysiological recordings show that electrical stimulation of the supraorbital nerve evokes early and late excitatory responses in these muscles, respectively known as the R1 and R2 components of the blink reflex 12A4. Mechanical or electrical stimulation of the corneal mucosa evokes a late response (corneal reflex) similar to R21,19, but with longer latency and duration 2,21. R1 is supposed to be mediated by oligosynaptic i n t e r n e u r o n a l relays in the pons, while R2 and the corneal reflex are mediated by polysynaptic b u l b o p o n t i n e circuits 13,2529. Although less consistently obtained, a supraorbital-abducens reflex 3 and a corneopterygoid reflex 22 have also been reported. This paper describes an inhibitory reflex recorded from the masseter and temporal muscles following
electrical stimulation of the supraorbital region in normal subjects. This reflex shows features which are different from the inhibition commonly exerted by intra- and perioral sensory stimulationl°,tlA6: it is evoked only by high-intensity noxious stimuli and it usually consists of a late single silent period (SP), with similar features and possibly the same central circuits of the second silent period which follows 'oral' stimulation. MATERIALS AND METHODS Experiments were carried out in 11 normal volunteers (25-40 years) of either sex, after informed consent was granted. The experiments were conducted while subjects sat on a dentist chair with a head-rest. Single squarewave negative pulses (0.1-0.5 ms, 10-70 m A ) were delivered through a pair of surface electrodes to the skin overlying the supraorbital nerve close to the supraorbital notch. The corneal mucosa was stimulated
Correspondence: M. Manfredi, Dipartimento di Scienze Neurologiche, Universita' di Roma, Viale Universita', 30, 00185 Roma, Italy, 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)
299 either mechanically, with a metal sphere (2 mm diameter) connected to the trigger circuit 24 or electrically, by means of a fine cotton thread emerging from a glass pipette filled with saline-soaked gauze and connected to the cathode of the stimulator; the anode was connected to the earlobeL Single square-wave pulses (1 ms, 80-2000~A) were used. E M G activity was recorded by surface electrodes or non-insulated needles from masseter, temporal and orbicularis oculi muscles on both sides. Signals were amplified (band width 20-5000 Hz), full waverectified, averaged and stored on floppy disks (Biopotential Analyzer Software Interactive System, OTE). Subjects were asked to clench their teeth in order to produce maximal E M G activity and to maintain it for periods of 1 s, with the aid of visual and auditory feed-back. The contractions were serially repeated after 10-30 s of rest; the E M G signals were averaged to provide a background level of E M G activity. Provided that stimuli of adequate intensity were delivered, 8-32 averaged trials were sufficient to yield good visualization and accurate measurements of the silent period (SP). Latencies and duration of SPs w e r e measured at the point of crossing between the inhibitory shift and a baseline indicating 80% of the background level of E M G activity (Fig. 4). SPs' areas were automatically computed and expressed both as absolute arbitrary units (AUs) and as percentage of background EMG. The reflex threshold was defined as the lowest stimulus intensity evoking, in single trials, pauses of electrical silence (independently from their duration) within the latency range of the SP and, in the averaged signal, a 50% suppression of the background EMG. Five subjects underwent local anaesthetic block of the supraorbital nerve. Supramaximal stimuli were delivered through a pair of fine insulated needles with a 3 mm bare tip inserted subcutaneously 15 mm apart along the course of the nerve. Prior to the block, signals were recorded from the ipsilateral masseter and orbicularis oculi muscle and averaged (16 trials), thus providing a baseline for SP and the blink reflex. Immediately afterwards, 1.5-2 ml of 1% lignocaine were injected around the stimulating electrodes. Stimulation and recording procedures were unchanged. Following the injection, recordings were repeated every 4 min until the complete disappearance of the reflex responses.
Conditioning experiments with the double shock technique were performed in 4 subjects. Supramaximal paired stimuli (100 ms interval) were delivered to the supraorbital nerve. This interstimulus interval was chosen because it yielded the best differential effect on the 'oral' early and late silent periods without overlapping of responses to first and second shockX The trial was repeated 16 times. The area and duration of the averaged test response (second shock) were compared with the unconditioned response's (first shock). In order to study the interaction between the two afferent volleys, the same procedure was repeated after 15 min by delivering the first shock to the supraorbital nerve and the second one to the ipsilateral infraorbital nerve; after a further 15 min the sequence of shocks was reversed. Statistical significance was evaluated with the Student's t-test.
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300 RESULTS Responses to stimulation o f the ophthalmic division Fig. 1 shows the effect of supraorbital stimulation on the orbicularis oculi, temporal and masseter muscles. At rest, excitatory responses could be evoked only in the orbicularis oculi muscle (Fig. 1A). When the subject clenched his teeth (Fig. 1B), an inhibitory response in the masticatory muscles became evident in 10 out of 11 cases. The inhibition took place between 35 and 75 ms after supraorbital stimulation. No significant differences between temporalis and masseter or between ipsi- and contralateral homonimous muscles were observed (Table I). The threshold for the SP was 4.2 times the sensory threshold and 3.4 times the threshold for R2. SP threshold stimuli were always reported as painful and rated 3 - 4 in an arbitrary pain scale of 5 steps 7. In half of the subjects supramaximal stimuli also induced an early (10-25 ms) attenuation of background E M G , although never amounting to electric silence. Electrical stimulation of the corneal mucosa evoked a suppression of the background E M G activity in 4 out of 6 subjects. However, the threshold was more than 8 times the sensory threshold or the corneal reflex threshold. The subjects often perceived sensations from the surrounding skin or the earlobe, and occasionally displayed an early E M G activity (Rl-like) in the ipsilateral orbicularis oculi. Mechanical stimuli applied to the corneal mucosa evoked corneal reflexes but failed to induce reproducible pauses in the masseter activity. It was concluded that the SPs observed with electrical stimulation of the cornea were possibly due to stimulus spread.
Silent periods to 'oral' stimulation Fig. 2 shows the responses to stimulation of various structures innervated by the trigeminal nerve and of an extratrigeminal territory. As expected, stimulation of the infraorbital nerve, of the labial mucosa and of the central incisor (Fig. 2 B - D ) at 2 - 3 times the sensory threshold, evoked a double silent period (SP1 and SP2) similar to previously reported 'oral' SPs5,10,16. Supramaximal stimulation of the skin on the lateral aspect of the neck (C3) did not induce any modification in background E M G (Fig. 2E). Table II summarises the features of late SPs following either supraorbital or infraorbital stimulation, the latter being taken as representative of the 'oral' SP2s. The two reflexes were fairly similar, the only remarkable difference between them corresponding to the threshold values, which were significantly lower for the infraorbital-SP (P < 0.01).
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301 TABLE II
Comparison between 'oral' SP2 and supraorbital-SP
were still present, although the pain sensation evoked by the stimulus had already disappeared. The amplitude of the reflexes progressively decreased,
Number of subjects with definite responses
Reflex-threshold ( x sensory threshold) Latency (ms) Duration (ms) Area (AUs)
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2.35 + 0.94 43 + 2.67 40 _ 5.8 95.5 + 33
4.17 +_ 1.60 36 + 2.47 38 + 8.2 63.8 + 40
Anaesthetic block Fig. 3 shows the effect of anaesthetic infiltration around the supraorbital nerve on the SP and the blink reflex. Four minutes after the block both reflexes
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Latency gain and habituation By increasing the intensity of the supraorbital nerve stimulation, the latency of SP response became consistently shorter (Fig. 4A). The difference between responses to supramaximal and threshold stimuli (8 ms + 6 S.D.) was statistically significant (P
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Fig. 4. Latency gain and habituation. A: stimulation of the supraorbital nerve at threshold (top trace) and at tolerance (bottom trace) intensity. B: random stimulation at a low rate (top trace) and repetitive 1 Hz stimulation (bottom trace) of the supraorbital nerve. Recordings from ipsilateral masseter. Averages of 16 rectified responses. Sweep 200 ms; sensitivity 200 /tV. A baseline indicating the 80% of background EMG level is superimposed on each trace (arrowheads). Arrows and hatching indicate SP-latencies and SP-areas, respectively.
302 < 0.01). The latencies of R1 and R2 concurrently fell by 0.6 ms and 15 ms respectively, values which correspond to those previously reported2,29. The rate of habituation was investigated by comparing the averaged SP's areas in response to 16 low frequency random stimuli and to 16 repetitive 1 Hz stimuli. During repetitive stimulation (Fig. 4B), the response was reduced by 58% (+ 34 S.D.); the difference was statistically significant (P < 0.001). As expected, R1 was not significantly affected, while R2 completely disappeared after the third or fourth stimulus.
the supraorbital nerve completely abolished the test SP (Fig. 5A). The same sequence delivered to the infraorbital nerve markedly suppressed the test SP2, but left unaffected the test SP1 (Fig. 5B). Similarly, a conditioning infraorbital shock completely suppressed the test supraorbital-SP (Fig. 5D), while a conditioning supraorbital shock only suppressed the infraorbital-SP2 but not SP1 (Fig. 5C). The degree of suppression of the test SP2 varied among subjects, but it is significant that both supra- and infraorbital conditionings were equally effective in the same subject.
Excitability and interaction
DISCUSSION
Fig. 5 shows the results of double shock stimulation. Paired stimuli delivered at a 100 ms interval to
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Stimuli slightly above 4,10 or below 18,2°,3°, the threshold for pain, delivered to the tongue H, teethS, Is, gums a°,3°, lips 1°, infraorbital nerve23, 3°, mental nerve 5,23 or the intracranial portion of the trigeminal nerve 6, evoke a double silent period of the masseter and temporal muscles. The latency shows some variation according to the site of stimulation, but it never exceeds 17 ms 16. Stimulation outside the above-mentioned structures, such as the ophthalmic division or the cranial cervical dermatomes, has been repeatedly reported to be ineffective1°, 30. On the contrary, we have been able to record in 90% of subjects a late silent period from the jaw elevators of both sides following stimulation of the supraorbital nerve. The different results obtained by previous investigators can be explained by the high-stimulus intensities necessary to evoke the response, which were frankly painful to all the subjects tested. Also, the absence or inconsistency of an early inhibition, and the habituation of the late SP, could give the impression of a negative result. The afferents responsible for the supraorbital-SP might belong to the small-myelinated (A6) group, since only noxious stimuli were able to elicit the reflex. However, the anaesthetic block affected the supraorbital-SP to the same extent and with the same time course as the blink reflex. Both components of the blink reflex are supposed to be mediated by cutaneous fibres26, 2s and indirect evidence has been provided that the conduction velocity of the afferents for R16,27 and for R227 falls within the/3 range. The assumption that the afferents subserving the SP were myelinated fibres of intermediate diameter, could be
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nerve (B, D). After 100 ms a second (test) shock is delivered to the supraorbital nerve (A, D) or the infraorbital nerve (B, C). Recordings from ipsilateral masseter. Averages of 16 rectified responses. Sweep 200 ms; sensitivity 200 ktV. Arrows indicate timing of first and second shock.
303 indirectly supported by the absence of a significant silent period following corneal stimulation, since the cornea is innervated by small myelinated and unmyelinated (C) fibres onlylS. It is possible that a great number of afferents need to be activated, thus creating a large spatial summation at some synapse, in order to obtain the reflex, which is otherwise absent following a weaker input. The question of the fibre group mediating the SP cannot, therefore, be definitely settled until direct measure of the conduction velocity is obtained. The latency gain exhibited by a reflex when the stimulus intensity increases from threshold to supramaximal level is a function of the number of interneurones in the reflex circuit, owing to spatial summation taking place at each synapse. In the case of the blink reflex, which shares the afferent branch with the SP, the latency gain of R1 (oligosynaptic) is clearly much smaller than that of R2 (polysynaptic) 2,13,2s,29. The supraorbital-SP showed a latency gain of some 8 ms, which is intermediate between those observed for R1 and R2. This would indicate that the SP response is mediated by an intermediate number of interneurones. The same conclusion could be drawn from the effect of repetitive stimulation. The supraorbital-SP habituated more rapidly than R1 but less than the R2 component of the blink reflex. In this regard, however, any direct comparison between an inhibitory and an excitatory reflex is obscured by the fact that the former is recorded during voluntary contraction of the muscle, i.e. a condition wherein motoneurones and interneurones are facilitated by the pyramidal activation 17. The supraorbital-SP shares the efferent branch of the reflex arc with the 'oral' SP1 and SP2. Both latency gain and habituation of supraorbital-
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SP were comparable to those reported for the SP2 following lip, tooth and mental nerve stimulationS-10. Furthermore, the recovery after double-shock stimulation shows that the test supraorbital-SP is completely suppressed by a conditioning stimulus delivered 100 ms earlier. The same behaviour is shown by the SP2 to 'oral' stimulation, while SP1 is unaffectedS. These results point at a similar multisynaptic organization for the two late inhibitory reflexes. Finally, interaction experiments showed that a conditioning stimulus delivered to the infraorbital nerve completely abolishes the supraorbital-SP, whereas a conditioning stimulus delivered to the supraorbital nerve suppresses only SP2 but not SP1 to infraorbital stimulation. This confirms a previous hypothesis5,10 which suggested that SP1 and SP2 responses to 'oral' stimuli are mediated by separate neuronal nets and implies that the same interneurons are shared by SP2 and the supraorbital-SP. Findings in patients with brainstem lesions have indicated that the 'oral' SPs are mediated entirely at pons level 23. The same should apply, therefore, to the supraorbital-SP. It is not yet altogether clear whether the 'oral' SPs subserve a defense reaction or a masticatory mechanism. It is even more difficult to understand the functional significance of a reflex inhibition of the masticatory muscles evoked by stimulation of the ophthalmic division. The different characteristics of early and late SPs shown in the present study support the view that they exert different functional roles. ACKNOWLEDGEMENTS This work was supported by a grant from the Consiglio Nazionale delle Ricerche, Roma, PF Medicina preventiva e riabilitativa SP8.
4 Bratzlavsky, M., De Boever, J. and Vandeer Eecken, H., Tooth pulpal reflexes in jaw musculature in man, Arch. Oral. Biol., 21 (1976) 491-493. 5 Cruccu, G., Agostino, R., Fornarelli, M., Inghilleri, M. and Manfredi, M., Recovery cycle of the masseter inhibitory reflex in man, Neurosci. Lett., 49 (1984) 63-68. 6 Cruccu, G. and Bowsher, D., Intracranial stimulation of trigeminal nerve in man. II. Reflex responses, J. Neurol. Neurosurg. Psychiat., 49 (1986). 7 Cruccu, G., Fornarelli, M., Inghilleri, M. and Manfredi, M., The limits of tooth pulp evoked potentials for pain
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