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Combined meeting of the French Society of clinical neurophysiology, Belgian society of clinical neurophysiology and Belgian society of EMG and clinical neurophysiology
Electroencephalographv and clinwal Neurophvswlogv, 199 I, 78:88 P - 90 P ,i 1991 Elsevier Scientific Publishers Irehmd, Ltd. 0013-4649/91/$03.50
88P
EEG 90668 Society
proceedings
Combined meeting of the French Society of Clinical Neurophysiology, Belgian Society of Clinical Neurophysiology and Belgian Society of EMG and Clinical Neurophysiology Brussels, 8-9 June 1990
Secretary." Prof. F. Mauguiere Hapital Neurologique. 59 Boulevard Pinel. 69003 Lyon (France) (Received for publication: 12 November 1990)
1. Experimental models of clinical pain. - G. Guilbaud (INSERM U 161, Paris)
3. Electrophysiological investigation of painful thalamic syndrnmes in man. - F. Maugui6re and J.E. Desmedt (Lyon and Brussels)
For a better understanding of clinical pain several groups involved in the study of basic pain mechanisms have proposed the use of various experimental models close to clinical situations. They are based either on neurogenic or inflammatory processes. Data obtained with three of these models will be developed in the paper: rats rendered arthritic by Freund's adjuvant injected into the tail, rats with an intraplantar injection of carrageenin in one hind paw, rats with a moderate ligature of one common sciatic nerve. The various pharmacological approaches revealed dramatic changes of the analgesic effects of morphine and other opioid substances, and a spectacular modification of the endogenous opioid reactivity. A further enhancement of the initial hyperalgesia was observed with high doses (1-3 m g / k g i.v.) of naloxone (known as an antagonist of morphine), contrasting with the paradoxical analgesia induced with low doses (peaking up for 3 g / k g i.v.). Electrophysiological studies emphasized dramatic changes of neuronal responsiveness in structures involved in the transmission of the nociceptive messages. In each of these models electrophysiological data provided new insights on the physiopathological mechanisms of the related clinical pain.
In 30 patients with a thalamic vascular lesion and clinical somatosensory disturbances in the opposite hemibody without hemiplegia, 4 nosological groups were identified: group 1 had no central pain but complete hemianaesthesia and loss of cortical somatosensory evoked potentials (SEPs) on the affected side (analgic thalamic syndrome); group 2 had central pain, severe hypoesthesia, and loss of cortical SEPs; group 3 had central pain and hypoesthesia, with cortical SEPs present, although reduced or delayed on the affected side: group 4 had central pain with preserved touch and joint sensations and normal SEPs (pure algesic thalamic syndrome). Clinical signs and SEP titration of the actual involvement of lemniscal pathways in these 4 groups of patients with thalamic syndrome are discussed in relation to current pathophysiology of central pain.
2. Novel approaches in the development of new analgesics. - B.P. Roques (Paris) A recently developed series of highly selective and systemically active 8 agonists such as Tyr-X-Gly-Phe-Leu-Thr(OtBu), with X = D. Ser (OtBu) in BUBU and X-DCys(OtBu) in BUBUC, and complete inhibitors of enkephalin metabolism (Kelatorphan, RB-38A, PC 12) have enabled the major role played by ,u-opioid receptors in supraspinal analgesia to be demonstrated. This is in agreement with the results of in vivo/*-receptor occupancy measured by taking into account the cross-reactivity of the 6 ligands for ,u sites. In contrast ,u and 8 binding sites seem to act independently to control pain at the spinal level. Strong analgesic effects, especially in arthritic rats, can also be obtained by complete protection of tonically or phasically released endogenous enkephalins with mixed inhibitors such as RB38A. Chronic i.c.v, administration of the # agonist D A G O led to a severe naloxone precipitated withdrawal syndrome whilst a weak dependence was seen with the 8 agonist, D S T B U L E T or with RB38A. Moreover, mixed inhibitors did not induce any significant respiratory depression. All these data emphasize the interest in developing 8 agonists and mixed inhibitors with appropriate bioavailability for clinical evaluation.
4. Issues on pain assessment and related psychologic factors. - F. Boureau, M. Lnu and J.F. Doubr6re (Paris) Pain is a complex, multidimensional and multifactorial neuropsychological phenomenon with sensory-discriminative, affective, cognitive and behavioural components. Issues on pain assessment are related to the objective evaluation of a subjective phenomenon. Different levels of evaluation are to be considered. Some methods like visual analog scales, numerical scales and verbal permit a global pain estimation. The aim of other methods like the McGill Pain Questionnaire is a quantitative and qualitative evaluation of the sensory and affective pain components. The measure of objective behavioural changes is an interesting approach, but at the present time there is no valid, simple and commonly, used method. There is also a need for methods permitting a better exploration of a pain, and in particular a selective evaluation of organic and functional factors. The limits of psychological factor evaluation are reported.
5. Clinical exploration of nociception with the use of reflexologic techniques. - J.C. Wilier (Lab. de Neurophysiologie, Facult~ de M~decine Pitid-Salp$tri~re, Paris) A method is described which allows an objective and specific exploration of an experimental pain in man by using some electrophysiological features of cutaneous reflexes. It can be summarized as follows: in a normal trained volunteer we studied simultaneously the
F R E N C H / BELGIAN SOCIETIES C O M B I N E D M E E T I N G recruitment curves of the nociceptive flexion reflex of a knee-flexor nmscle (biceps femoris) and of pain elicited by electrical stimulation of the ipsilateral sural nerve at the ankle. The reflex threshold (Tr) was closely related to the pain threshold (Tp) around a similar value (10 mA). The threshold of the maximal recruitment of the reflex (I mr) and that of tolerance to pain (Tpt) were found to be close to 33 mA. These values were reliably reproducible in one subject from one session to the other, and in all subjects with minimal inter-individual variations and without any significant inter-sex difference. These close relationships between Tr and Tp and between T m r and Tpt respectively constituted the basis of the methodology for investigating objectively the h u m a n nociceptive reactions. This methodology is applied to studying the spinal mechanisms of morphine analgesia when the drug is given either intravenously to normal subjects and paraplegic patients or epidurally to patients with acute postoperative pain. The resulting data strongly validate the model since they show that pain and the nociceptive reflex are similarly depressed by morphine in a dose-response fashion. The data also show that the spinal level is one of the important sites of the mechanisms of morphine-induced analgesia since this drug is found to strongl?, depress selectively the nociceptive transmission directly at the spinal level. I~inally, the method is applied for investigating the nociceptive reactions in patients affected either by a pathological lack of pain sensation or, by contrast, in patients complaining of acute or chronic pain of various origins. To conclude, since the nociceptive flexion reflex can be considered as a specific and objective physiological correlate of a pain sensation, it can be successfully employed as a useful tool for investigating some aspecls of the human nociceptive reactions in both experimental and pathological situations.
6. Electrophysiological studies in cervico-brachial neuralgia. - S. Tranier ", A. Foucher ", E. Gozlan b, B. Pelleray b, M. Sev~ne b A. Durey b and F. Liot ~ (" H6pital A. Par~, Boulogne, and b Hdpital Fuch, Suresnes)
Nine patients with unilateral cervico-brachial neuralgia (CBN) were studied in order to gain information regarding application of the ttoffman reflex (H) to the upper limbs. This group (group It0) is compared with a control group of 10 healthy subjects (group Ic). The H reflex and the M direct responses of the flexor carpi radialis were evoked and recorded by surface electrodes. The median nerve was stimulated in the cubital fossa. Amplitudes were measured from the negative peak to the positive peak and latencies from the beginning of the stimulus artifact to the start of the maximal H and M responses. A right-left difference in H and M latencies (H-REd, M-RI,d) and an H reflex amplitude ratio of the painful over the non-painful side (H-A ratio) were evaluated. This electrophysiological stud~, was completed by classic electromyography, motor and sensory conduction velocities and, in some patients, by somatosensory evoked potentials. The M-REd was not significantly different, but the H-REd (1c-0.33+_(L27 msec: lip 1.83_+1.56 msec) and the H ratio ( 1 c 0.77+0.07: 1 1 p - 0 . 5 1 ± 0 . 3 5 ) were statistically different between groups ( P < 0.01 and P < 0.02). The presented studies are useful to dvtermine the presence and severity of sixth or seventh cervical nerve root pathology.
7. Deep brain stimulation in the treatment of chronic pain in man: where and why? - J. Gybels and R. Kupers (Louvain)
In current clinical practice, two brain structures are stimulated for the relief of chronic pain: the somatosensory thalamic nuclei (VPLVPM) and the periventricular and periaqueductal grey matter (PVGPAGI. Whereas stimulation of the VPL-VPM is almost exclusively
89P used for the treatment of deafferentation pain, stimulation of the PVG-PAG is mostly used in cases of nociceptive pain. Here we present our results of VPL-VPM stimulation in 36 patients with deafferentation pain. Initial pain relief was obtained in 61% of them. Today, after a mean follow-up of more than 4 years, 30% are still pain-free. This success rate was found to be lower than the mean reported success rate of 57%, based on a survey of the world literature. Reviewing the literature, it was apparent that the reported success rates vary considerably between different authors. Some tentative explanations are given for this large discrepancy in success rate. The mechanisms by which electrical stimulation of the VPL-VPM suppresses deafferentation pain remain to be elucidated. Recent clinical and experimental findings suggest that a dopaminergic mechanism might be involved.
8. Pericranial as well as Achilles tendon pressure-pain thresholds are decreased in tension-type headache. - J. Schoenen, P. Gerard, D. Bottin and M. Lenaerts (Universi~ of Liege, Liege)
The precise pathogenesis of tension-type headache remains unknown. Deficient activation of endogenous pain control systems has been proposed as a possible mechanism (Sicuteri 1986). Tender spots over pericranial muscles are frequently found in affected patients (Lous and Olesen 1982). We have assessed pain sensitivity bilaterally at various pericranial spots (temples, forehead, suboccipital region) and at the Achilles tendon, using a pressure algometer. C o m m o n migraineurs in headache-free intervals (n = 10) and patients suffering from chronic tension-type headache (n = 32) were compared with a group of age- and sex-matched healthy volunteers (n = 20). At each spot, the last of 4 measurements performed at 15 sec intervals was taken into consideration. No significant differences were found between the control group and the group of patients diagnosed as having migraine without aura. However, the pain threshold to pressure. expressed in kilo-Pascals (kPa), was on average significantly lower in tension-type headache than in the two other groups. This was the case not only at the various pericranial spots, but also at the level of the Achilles tendon. For instance, the mean threshold over the right temple was 2.99_+72 in controls, 181 _+68 in tension-type headache ( P < 0.005); at the Achilles tendon, corresponding values were 319_+ 102 and 299_+61 ( P < 0 . 0 1 ) . There were no significant right-left differences. These results indicate that patients suffering from chronic tension-type headache are characterized by a decreased pressure-pain threshold in pericranial structures, as well as at the Achilles tendon. This might be due to inappropriate functioning of central pain control systems (Olesen and Langemark 1988).
9. Clinical neurophysiology in migraine and tension-~pe headaches. J. Schoenen (Universi~ of Liege, Liege)
In so-called functional headaches, neurophysiological studies have a pathophysiological and diagnostic interest. The contingent negative variation (CNV) has an increased amplitude and a decreased habituation in migraine without aura between attacks. The CNV amplitude normalizes during therapy with beta-blockers and there is a positive correlation between the clinical response to these drugs and the initial amplitude of the CNV, We have shown that the threshold for activation after transcortical electromagnetic stimulation is increased in migraine with aura over the usually involved hemisphere, but not on the other side or in migraine withoul aura. Scalp distributions but not latencies, of some components of auditory event-related potentials differ between migraineurs and controls. Topographical EEG mapping during attacks of migraine with aura demonstrates posterior unilateral decrease of alpha power and increase of theta-delta power. Conversely, during attacks of migraine without aura, EEG brain
90P mapping discloses only unilateral reduction of alpha power, which may persist up to 24 h. In tension-type headache, EMG levels of pericranial muscles are on average increased. However. in individual patients, in order to detect an abnormal value, one has to measure several pericranial muscles under several conditions. The most striking abnormality in tension-type headache is the reduction or disappearance of the late exteroceptive silent period in temporalis muscle. This is not correlated with pressure pain thresholds, which are on average decreased, or with EMG levels.
10. Temporalis exteroceptive silent period in headache. - J. Schoenen, J. Sianard-Gainko, P. Gerard and D. Bottin (Universi~ of Liege, Liege) Early (ES1) and late (ES2) exteroceptive suppression periods elicited by electrical stimulation of the labial commissure during tooth clenching were recorded over the temporalis muscle in 45 headache patients (25 tension headache sufferers, 20 migraineurs) and 22 healthy controls. The mean duration of ES2 was significantly reduced in tension headache when compared to migraine or controls. A prospective study of 33 patients with tension-type headache disclosed no correlation between ES2 duration and pressure tenderness over the temples or basal EMG activity of frontalis muscles at rest. In patients treated with EMG biofeedback, the duration of temporalis ES2 was protracted after treatment and this correlated with clinical improvement. In women suffering from menstrual headaches, the reduction of temporalis ES during the menses was inversely correlated with the oestrogen/progesterone ratio in plasma. In healthy volunteers, ES2 was increased after oral administration of the serotonin antagonist methysergide. EMG analysis of temporalis late exteroceptive suppression might thus be a helpful diagnostic tool in functional headaches. Reduction of ES2 suggests that there is deficient activation (or excessive inhibition) of ponto-bulbar inhibitory interneurones, which receive a strong limbic input. The latter might act through aminergic, hormone-regulated, pathways.
1 I. Nociceptive flexion reflexes as an aid in the evaluation of neurosurgical procedures for pain and spasticity. - L. Garcia-Larrea, M. Sindou and F. Maugui~re Flexion reflexes have proved to be a useful tool for the electrophysiological assessment of nociceptive mechanisms in man and animals: however, these responses are still very seldom used in clinical practice. We present several examples of the application of nociceptive flexion reflexes (RIll response) to be objective evaluation of neurosurgical procedure aiming at alleviating pain or spasticity. After implantation of systems for analgesic neurostimulation (AN), nociceptive reflex recording allows the objectivation of the neurophysiological effects of AN on the spinal circuits implicated in nociceptive
SOCIETY P R O C E E D I N G S responses. Thus, significant attenuation of nociceptive reflexes by AN provides objective evidence of the depressor effect of neurostimulation upon the spinal mechanisms involved in pain transmission. In our series, the proportion of patients clinically alleviated by AN was significantly higher when this procedure was able to depress nociceptive reflexes. The selectivity of neurosurgical procedures aiming at interrupting the nociceptive pathways without affecting the dorsal column system may be demonstrated by the combination of flexion nociceptive reflexes and somatosensory evoked potentials (SEPs). Thus. after microsurgical procedures for pain relief at the dorsal root entry zone, the abolition of flexion reflexes with preservation of cortical SEPs is the unique pattern demonstrating a selective lesion of nociceptive pathways at that level. Flexor reflexes are exaggerated in patients with spasticity due to spinal lesions. The intrathecal administration of baclofen entails a dramatic depression of reflexes which parallels the clinical relief of spasticity. Since flexor reflex measurements are objective, they can be used as a 'template' to quantify the degree of improvement, as well as to adjust drug dosages so as to determine the minimal amount of drug needed in a given patient to achieve optimal effects.
12. Detection and quantification of opiate receptors in man by positron emission tomography. Potential applications to the study of pain. B. Sadzot a H.S. Mayberg b and J.J. Frost b (, Dept. of Neurology and Cyclotron Research Center, University of Liege, Liege, and b Division of Nuclear Medicine, Johns Hopkins Medical Institution, Baltimore, MD, U.S.A.) Positron emission tomography allows measurement of the local concentration of a radioactive tracer. Because of its high sensitivity and the radioligands that are available, it is particularly well suited for the atraumatic detection and quantification of receptors in vivo. 11 After the administration of [ C]carfentanll, an extremely potent 11 • agonist at mu opiate receptors or [ C]daprenorphme, a weak partial agonist that binds to mu, delta and kappa opiate receptors, the regional concentration of radioactive tracer in the brain parallels the known distribution of opiate receptors: high concentrations in the thalamus and the cingulate, and intermediate concentrations in most cortical areas except in the occipital cortex where very low concentrations are measured. With the sequential administration of [11C]diprenorphine, mathematical modelling allows regional quantitative estimates of opiate receptor density and affinity in vivo. Opiate receptors play a major role in pain perception. Taking into account various methodological problems that are not always specific to PET, it will be possible to design studies aimed at evaluation the regulation of opiate receptors as a function of pain perception or drug treatment.
88P
EEG 90668 Society
proceedings
Combined meeting of the French Society of Clinical Neurophysiology, Belgian Society of Clinical Neurophysiology and Belgian Society of EMG and Clinical Neurophysiology Brussels, 8-9 June 1990
Secretary." Prof. F. Mauguiere Hapital Neurologique. 59 Boulevard Pinel. 69003 Lyon (France) (Received for publication: 12 November 1990)
1. Experimental models of clinical pain. - G. Guilbaud (INSERM U 161, Paris)
3. Electrophysiological investigation of painful thalamic syndrnmes in man. - F. Maugui6re and J.E. Desmedt (Lyon and Brussels)
For a better understanding of clinical pain several groups involved in the study of basic pain mechanisms have proposed the use of various experimental models close to clinical situations. They are based either on neurogenic or inflammatory processes. Data obtained with three of these models will be developed in the paper: rats rendered arthritic by Freund's adjuvant injected into the tail, rats with an intraplantar injection of carrageenin in one hind paw, rats with a moderate ligature of one common sciatic nerve. The various pharmacological approaches revealed dramatic changes of the analgesic effects of morphine and other opioid substances, and a spectacular modification of the endogenous opioid reactivity. A further enhancement of the initial hyperalgesia was observed with high doses (1-3 m g / k g i.v.) of naloxone (known as an antagonist of morphine), contrasting with the paradoxical analgesia induced with low doses (peaking up for 3 g / k g i.v.). Electrophysiological studies emphasized dramatic changes of neuronal responsiveness in structures involved in the transmission of the nociceptive messages. In each of these models electrophysiological data provided new insights on the physiopathological mechanisms of the related clinical pain.
In 30 patients with a thalamic vascular lesion and clinical somatosensory disturbances in the opposite hemibody without hemiplegia, 4 nosological groups were identified: group 1 had no central pain but complete hemianaesthesia and loss of cortical somatosensory evoked potentials (SEPs) on the affected side (analgic thalamic syndrome); group 2 had central pain, severe hypoesthesia, and loss of cortical SEPs; group 3 had central pain and hypoesthesia, with cortical SEPs present, although reduced or delayed on the affected side: group 4 had central pain with preserved touch and joint sensations and normal SEPs (pure algesic thalamic syndrome). Clinical signs and SEP titration of the actual involvement of lemniscal pathways in these 4 groups of patients with thalamic syndrome are discussed in relation to current pathophysiology of central pain.
2. Novel approaches in the development of new analgesics. - B.P. Roques (Paris) A recently developed series of highly selective and systemically active 8 agonists such as Tyr-X-Gly-Phe-Leu-Thr(OtBu), with X = D. Ser (OtBu) in BUBU and X-DCys(OtBu) in BUBUC, and complete inhibitors of enkephalin metabolism (Kelatorphan, RB-38A, PC 12) have enabled the major role played by ,u-opioid receptors in supraspinal analgesia to be demonstrated. This is in agreement with the results of in vivo/*-receptor occupancy measured by taking into account the cross-reactivity of the 6 ligands for ,u sites. In contrast ,u and 8 binding sites seem to act independently to control pain at the spinal level. Strong analgesic effects, especially in arthritic rats, can also be obtained by complete protection of tonically or phasically released endogenous enkephalins with mixed inhibitors such as RB38A. Chronic i.c.v, administration of the # agonist D A G O led to a severe naloxone precipitated withdrawal syndrome whilst a weak dependence was seen with the 8 agonist, D S T B U L E T or with RB38A. Moreover, mixed inhibitors did not induce any significant respiratory depression. All these data emphasize the interest in developing 8 agonists and mixed inhibitors with appropriate bioavailability for clinical evaluation.
4. Issues on pain assessment and related psychologic factors. - F. Boureau, M. Lnu and J.F. Doubr6re (Paris) Pain is a complex, multidimensional and multifactorial neuropsychological phenomenon with sensory-discriminative, affective, cognitive and behavioural components. Issues on pain assessment are related to the objective evaluation of a subjective phenomenon. Different levels of evaluation are to be considered. Some methods like visual analog scales, numerical scales and verbal permit a global pain estimation. The aim of other methods like the McGill Pain Questionnaire is a quantitative and qualitative evaluation of the sensory and affective pain components. The measure of objective behavioural changes is an interesting approach, but at the present time there is no valid, simple and commonly, used method. There is also a need for methods permitting a better exploration of a pain, and in particular a selective evaluation of organic and functional factors. The limits of psychological factor evaluation are reported.
5. Clinical exploration of nociception with the use of reflexologic techniques. - J.C. Wilier (Lab. de Neurophysiologie, Facult~ de M~decine Pitid-Salp$tri~re, Paris) A method is described which allows an objective and specific exploration of an experimental pain in man by using some electrophysiological features of cutaneous reflexes. It can be summarized as follows: in a normal trained volunteer we studied simultaneously the
F R E N C H / BELGIAN SOCIETIES C O M B I N E D M E E T I N G recruitment curves of the nociceptive flexion reflex of a knee-flexor nmscle (biceps femoris) and of pain elicited by electrical stimulation of the ipsilateral sural nerve at the ankle. The reflex threshold (Tr) was closely related to the pain threshold (Tp) around a similar value (10 mA). The threshold of the maximal recruitment of the reflex (I mr) and that of tolerance to pain (Tpt) were found to be close to 33 mA. These values were reliably reproducible in one subject from one session to the other, and in all subjects with minimal inter-individual variations and without any significant inter-sex difference. These close relationships between Tr and Tp and between T m r and Tpt respectively constituted the basis of the methodology for investigating objectively the h u m a n nociceptive reactions. This methodology is applied to studying the spinal mechanisms of morphine analgesia when the drug is given either intravenously to normal subjects and paraplegic patients or epidurally to patients with acute postoperative pain. The resulting data strongly validate the model since they show that pain and the nociceptive reflex are similarly depressed by morphine in a dose-response fashion. The data also show that the spinal level is one of the important sites of the mechanisms of morphine-induced analgesia since this drug is found to strongl?, depress selectively the nociceptive transmission directly at the spinal level. I~inally, the method is applied for investigating the nociceptive reactions in patients affected either by a pathological lack of pain sensation or, by contrast, in patients complaining of acute or chronic pain of various origins. To conclude, since the nociceptive flexion reflex can be considered as a specific and objective physiological correlate of a pain sensation, it can be successfully employed as a useful tool for investigating some aspecls of the human nociceptive reactions in both experimental and pathological situations.
6. Electrophysiological studies in cervico-brachial neuralgia. - S. Tranier ", A. Foucher ", E. Gozlan b, B. Pelleray b, M. Sev~ne b A. Durey b and F. Liot ~ (" H6pital A. Par~, Boulogne, and b Hdpital Fuch, Suresnes)
Nine patients with unilateral cervico-brachial neuralgia (CBN) were studied in order to gain information regarding application of the ttoffman reflex (H) to the upper limbs. This group (group It0) is compared with a control group of 10 healthy subjects (group Ic). The H reflex and the M direct responses of the flexor carpi radialis were evoked and recorded by surface electrodes. The median nerve was stimulated in the cubital fossa. Amplitudes were measured from the negative peak to the positive peak and latencies from the beginning of the stimulus artifact to the start of the maximal H and M responses. A right-left difference in H and M latencies (H-REd, M-RI,d) and an H reflex amplitude ratio of the painful over the non-painful side (H-A ratio) were evaluated. This electrophysiological stud~, was completed by classic electromyography, motor and sensory conduction velocities and, in some patients, by somatosensory evoked potentials. The M-REd was not significantly different, but the H-REd (1c-0.33+_(L27 msec: lip 1.83_+1.56 msec) and the H ratio ( 1 c 0.77+0.07: 1 1 p - 0 . 5 1 ± 0 . 3 5 ) were statistically different between groups ( P < 0.01 and P < 0.02). The presented studies are useful to dvtermine the presence and severity of sixth or seventh cervical nerve root pathology.
7. Deep brain stimulation in the treatment of chronic pain in man: where and why? - J. Gybels and R. Kupers (Louvain)
In current clinical practice, two brain structures are stimulated for the relief of chronic pain: the somatosensory thalamic nuclei (VPLVPM) and the periventricular and periaqueductal grey matter (PVGPAGI. Whereas stimulation of the VPL-VPM is almost exclusively
89P used for the treatment of deafferentation pain, stimulation of the PVG-PAG is mostly used in cases of nociceptive pain. Here we present our results of VPL-VPM stimulation in 36 patients with deafferentation pain. Initial pain relief was obtained in 61% of them. Today, after a mean follow-up of more than 4 years, 30% are still pain-free. This success rate was found to be lower than the mean reported success rate of 57%, based on a survey of the world literature. Reviewing the literature, it was apparent that the reported success rates vary considerably between different authors. Some tentative explanations are given for this large discrepancy in success rate. The mechanisms by which electrical stimulation of the VPL-VPM suppresses deafferentation pain remain to be elucidated. Recent clinical and experimental findings suggest that a dopaminergic mechanism might be involved.
8. Pericranial as well as Achilles tendon pressure-pain thresholds are decreased in tension-type headache. - J. Schoenen, P. Gerard, D. Bottin and M. Lenaerts (Universi~ of Liege, Liege)
The precise pathogenesis of tension-type headache remains unknown. Deficient activation of endogenous pain control systems has been proposed as a possible mechanism (Sicuteri 1986). Tender spots over pericranial muscles are frequently found in affected patients (Lous and Olesen 1982). We have assessed pain sensitivity bilaterally at various pericranial spots (temples, forehead, suboccipital region) and at the Achilles tendon, using a pressure algometer. C o m m o n migraineurs in headache-free intervals (n = 10) and patients suffering from chronic tension-type headache (n = 32) were compared with a group of age- and sex-matched healthy volunteers (n = 20). At each spot, the last of 4 measurements performed at 15 sec intervals was taken into consideration. No significant differences were found between the control group and the group of patients diagnosed as having migraine without aura. However, the pain threshold to pressure. expressed in kilo-Pascals (kPa), was on average significantly lower in tension-type headache than in the two other groups. This was the case not only at the various pericranial spots, but also at the level of the Achilles tendon. For instance, the mean threshold over the right temple was 2.99_+72 in controls, 181 _+68 in tension-type headache ( P < 0.005); at the Achilles tendon, corresponding values were 319_+ 102 and 299_+61 ( P < 0 . 0 1 ) . There were no significant right-left differences. These results indicate that patients suffering from chronic tension-type headache are characterized by a decreased pressure-pain threshold in pericranial structures, as well as at the Achilles tendon. This might be due to inappropriate functioning of central pain control systems (Olesen and Langemark 1988).
9. Clinical neurophysiology in migraine and tension-~pe headaches. J. Schoenen (Universi~ of Liege, Liege)
In so-called functional headaches, neurophysiological studies have a pathophysiological and diagnostic interest. The contingent negative variation (CNV) has an increased amplitude and a decreased habituation in migraine without aura between attacks. The CNV amplitude normalizes during therapy with beta-blockers and there is a positive correlation between the clinical response to these drugs and the initial amplitude of the CNV, We have shown that the threshold for activation after transcortical electromagnetic stimulation is increased in migraine with aura over the usually involved hemisphere, but not on the other side or in migraine withoul aura. Scalp distributions but not latencies, of some components of auditory event-related potentials differ between migraineurs and controls. Topographical EEG mapping during attacks of migraine with aura demonstrates posterior unilateral decrease of alpha power and increase of theta-delta power. Conversely, during attacks of migraine without aura, EEG brain
90P mapping discloses only unilateral reduction of alpha power, which may persist up to 24 h. In tension-type headache, EMG levels of pericranial muscles are on average increased. However. in individual patients, in order to detect an abnormal value, one has to measure several pericranial muscles under several conditions. The most striking abnormality in tension-type headache is the reduction or disappearance of the late exteroceptive silent period in temporalis muscle. This is not correlated with pressure pain thresholds, which are on average decreased, or with EMG levels.
10. Temporalis exteroceptive silent period in headache. - J. Schoenen, J. Sianard-Gainko, P. Gerard and D. Bottin (Universi~ of Liege, Liege) Early (ES1) and late (ES2) exteroceptive suppression periods elicited by electrical stimulation of the labial commissure during tooth clenching were recorded over the temporalis muscle in 45 headache patients (25 tension headache sufferers, 20 migraineurs) and 22 healthy controls. The mean duration of ES2 was significantly reduced in tension headache when compared to migraine or controls. A prospective study of 33 patients with tension-type headache disclosed no correlation between ES2 duration and pressure tenderness over the temples or basal EMG activity of frontalis muscles at rest. In patients treated with EMG biofeedback, the duration of temporalis ES2 was protracted after treatment and this correlated with clinical improvement. In women suffering from menstrual headaches, the reduction of temporalis ES during the menses was inversely correlated with the oestrogen/progesterone ratio in plasma. In healthy volunteers, ES2 was increased after oral administration of the serotonin antagonist methysergide. EMG analysis of temporalis late exteroceptive suppression might thus be a helpful diagnostic tool in functional headaches. Reduction of ES2 suggests that there is deficient activation (or excessive inhibition) of ponto-bulbar inhibitory interneurones, which receive a strong limbic input. The latter might act through aminergic, hormone-regulated, pathways.
1 I. Nociceptive flexion reflexes as an aid in the evaluation of neurosurgical procedures for pain and spasticity. - L. Garcia-Larrea, M. Sindou and F. Maugui~re Flexion reflexes have proved to be a useful tool for the electrophysiological assessment of nociceptive mechanisms in man and animals: however, these responses are still very seldom used in clinical practice. We present several examples of the application of nociceptive flexion reflexes (RIll response) to be objective evaluation of neurosurgical procedure aiming at alleviating pain or spasticity. After implantation of systems for analgesic neurostimulation (AN), nociceptive reflex recording allows the objectivation of the neurophysiological effects of AN on the spinal circuits implicated in nociceptive
SOCIETY P R O C E E D I N G S responses. Thus, significant attenuation of nociceptive reflexes by AN provides objective evidence of the depressor effect of neurostimulation upon the spinal mechanisms involved in pain transmission. In our series, the proportion of patients clinically alleviated by AN was significantly higher when this procedure was able to depress nociceptive reflexes. The selectivity of neurosurgical procedures aiming at interrupting the nociceptive pathways without affecting the dorsal column system may be demonstrated by the combination of flexion nociceptive reflexes and somatosensory evoked potentials (SEPs). Thus. after microsurgical procedures for pain relief at the dorsal root entry zone, the abolition of flexion reflexes with preservation of cortical SEPs is the unique pattern demonstrating a selective lesion of nociceptive pathways at that level. Flexor reflexes are exaggerated in patients with spasticity due to spinal lesions. The intrathecal administration of baclofen entails a dramatic depression of reflexes which parallels the clinical relief of spasticity. Since flexor reflex measurements are objective, they can be used as a 'template' to quantify the degree of improvement, as well as to adjust drug dosages so as to determine the minimal amount of drug needed in a given patient to achieve optimal effects.
12. Detection and quantification of opiate receptors in man by positron emission tomography. Potential applications to the study of pain. B. Sadzot a H.S. Mayberg b and J.J. Frost b (, Dept. of Neurology and Cyclotron Research Center, University of Liege, Liege, and b Division of Nuclear Medicine, Johns Hopkins Medical Institution, Baltimore, MD, U.S.A.) Positron emission tomography allows measurement of the local concentration of a radioactive tracer. Because of its high sensitivity and the radioligands that are available, it is particularly well suited for the atraumatic detection and quantification of receptors in vivo. 11 After the administration of [ C]carfentanll, an extremely potent 11 • agonist at mu opiate receptors or [ C]daprenorphme, a weak partial agonist that binds to mu, delta and kappa opiate receptors, the regional concentration of radioactive tracer in the brain parallels the known distribution of opiate receptors: high concentrations in the thalamus and the cingulate, and intermediate concentrations in most cortical areas except in the occipital cortex where very low concentrations are measured. With the sequential administration of [11C]diprenorphine, mathematical modelling allows regional quantitative estimates of opiate receptor density and affinity in vivo. Opiate receptors play a major role in pain perception. Taking into account various methodological problems that are not always specific to PET, it will be possible to design studies aimed at evaluation the regulation of opiate receptors as a function of pain perception or drug treatment.