Clinical utility of pain--laser evoked potentials.
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Evoked Potentials↗
Biomedical subjects
G Cruccu
Publications and source records attributed to G Cruccu.
EFNS guidelines on neuropathic pain assessment.
In September 2001, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim of evaluating the existing evidence about the methods of assessing neuropathic pain and its treatments. This review led to the development of guidelines to be used in the management of patients with neuropathic pain. In the clinical setting a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis. Nerve conduction studies and somatosensory-evoked potentials, which do not assess small fibre function, may demonstrate and localize a peripheral or central nervous lesion. A quantitative assessment of the nociceptive pathways is provided by quantitative sensory testing and laser-evoked potentials. To evaluate treatment efficacy in a patient and in controlled trials, the simplest psychometric scales and quality of life measures are probably the best methods. A laboratory measure of pain that by-passes the subjective report, and thus cognitive influences, is a hopeful aim for the future.
Europe↗
Topodiagnostic investigations on the sympathoexcitatory brain stem pathway using a new method of three dimensional brain stem mapping.
OBJECTIVES: To study the incompletely understood sympathoexcitatory pathway through the human brain stem, using a new method of three dimensional brain stem mapping on the basis of digitally postprocessed magnetic resonance imaging (MRI). METHODS: 258 consecutive patients presenting with acute signs of brain stem ischaemia underwent biplane T2 and EPI diffusion weighted MRI, with slice orientation parallel and perpendicular to a transversal slice selection of the stereotactic anatomical atlas of Schaltenbrand and Wahren, 1977. The individual slices were digitally normalised and projected onto the appropriate slices of the anatomical atlas. For correlation analysis lesions were imported into a three dimensional model of the human brain stem. RESULTS: 31 of the 258 patients had Horner's syndrome caused by acute brain stem ischaemia. Only four of the patients with Horner's syndrome had pontine infarctions, 12 had pontomedullary lesions, and 15 had medullary lesions. Correlation analysis showed significantly affected voxels in the dorsolateral medulla but not in the pons. A statistical comparison with infarct topology in patients with medullary lesions but without Horner's syndrome indicated that involvement of the medial and ventral part of affected voxels located in the ventrolateral medullary tegmentum was specific for Horner's syndrome. CONCLUSIONS: Based on this first in vivo topodiagnostic study, the central sympathoexcitatory pathway probably descends through the dorsal pons before converging on specific generators in the ventrolateral medullary tegmentum at a level below the IX and X nerve exits.
Aged↗
Unmyelinated trigeminal pathways as assessed by laser stimuli in humans.
Laser pulses excite superficial free nerve endings innervated by small-myelinated (Adelta) and unmyelinated (C) fibres. Whereas laser-evoked scalp potentials (LEPs) are now reliably used to assess function of the Adelta-fibre nociceptive pathways in patients with peripheral or central lesions, the selective activation of C-fibre receptors and recording of the related brain potentials remain difficult. To investigate trigeminal C-fibre function, we directed laser pulses to the facial skin and studied sensory perception and scalp evoked potentials related to Adelta- or C-fibre activation in healthy humans and patients--one having a bilateral facial palsy, two a trigeminal neuropathy, and two a Wallenberg syndrome. We also measured afferent conduction velocity and, with source analysis, studied the brain generators. Whereas laser pulses of low intensity and small irradiated area elicited pinprick sensations and standard Adelta-LEPs, laser pulses of very-low intensity and large irradiated area elicited warmth sensations and scalp potentials with a latency compatible with C-fibre conduction (negative wave 280 ms, positive wave 380 ms); the estimated conduction velocity was 1.2 m/s. The main waves of the scalp potentials originated from the anterior cingulate gyrus; they were preceded by activity in the opercular region and followed by activity in the insular region. The patient with bilateral facial palsy, who had absent trigeminal-facial reflexes, had normal Adelta- and C-related scalp potentials; the patients with trigeminal neuropathy, characterized by loss of myelinated and sparing of unmyelinated fibres, had absent Adelta- but normal C-related potentials; and the patients with Wallenberg syndrome had absent Adelta- and C-related potentials. We conclude that laser pulses with appropriate characteristics evoke brain potentials related to the selective activation of trigeminal nociceptive Adelta or thermal C fibres. The trigeminal territory yields rewarding LEP findings owing to the high density of thermal receptors and, because the short conduction distance, minimizes the problem of signal dispersion along slow-conducting unmyelinated afferents. The opercular-insular region and the cingulate gyrus are involved in the processing of C-fibre trigeminal inputs. The method we describe may prove useful in patients with lesions affecting the trigeminal thermal pain pathways.
Adult↗
Trigeminal responses to laser stimuli.
The majority of the studies on laser evoked potentials (LEPs) have been focused on hand and foot stimulations and only lately on the trigeminal system. Because of a high receptor density in the facial skin and the very short conduction distance, LEP recordings after trigeminal stimulation are easier and quicker than those after stimulation of the limb extremities. Laser pulses with a stimulus intensity close to perception threshold can evoke well-defined LEPs. Few trials are sufficient to yield stable and reproducible averages. Even ultralate LEPs related to the C-fibre input are comparatively easily obtained from the trigeminal territory. The brain generators of the main LEP waves are probably very close for the trigeminal and limb stimulations. Trigeminal LEPs have been found absent or delayed in patients with trigeminal neuralgia, trigeminal neuropathies, posterior fossa tumors, and brainstem infarctions or demyelinating plaques. Conversely, trigeminal LEPs appear to be enhanced in patients with migraine. High-intensity pulses directed to any trigeminal division also elicit reflex responses: a blink-like reflex in the orbicularis oculi and a single silent period in the contracting masseter muscle. The availability of a neurophysiological method of assessing function of the trigeminal nociceptive pathways reaching both the cerebral cortex and the brainstem reflex circuits, has provided new opportunities for investigating the pathophysiology of orofacial pain syndromes.
Blinking↗
Assessment of nociceptive trigeminal pathways by laser-evoked potentials and laser silent periods in patients with painful temporomandibular disorders.
We assessed the trigeminal nociceptive pathways in patients with painful temporomandibular disorders (TMD) and control subjects using a CO(2)-laser stimulator which provides a predominant activation of the nociceptive system. Fifteen patients with unilateral pain were examined in accordance with the Research Diagnostic Criteria for TMD and 30 gender- and age-matched individuals were included as a control group. Laser-evoked potentials (LEPs) and laser silent periods (LSPs) after stimulation of the perioral region (V2/V3) on the painful and non-painful sides were recorded in all subjects. LEPs were evoked by low-intensity pulses (1.5 x perception threshold (PTh)) and recorded from scalp electrodes at the vertex. LSPs were evoked by high-intensity pulses (4 x PTh) and recorded bilaterally from masseter muscles with surface electromyogram (EMG) electrodes. Subjects also assessed the stimulus intensity on a 0-10 rating scale. LEPs had normal latency but smaller amplitude in TMD patients compared to the control group (P<0.001). Side-to-side comparison within patients showed that LEP amplitude was even more reduced after stimulation on the painful than the non-painful side (P<0.001). TMD patients showed a significant side-asymmetry of the pre-stimulus EMG activity, with a smaller value in the muscle on the painful side (P<0.001). LSPs were completely absent bilaterally in 12 TMD patients and unilaterally in two patients; only one patient had normal and bilateral LSPs. TMD patients perceived the laser stimulus less intense on the painful than the non-painful side (P<0.05). We found suppression of cortical responses and brainstem reflexes elicited by a predominantly nociceptive input in TMD patients. These findings are consistent with recent experimental pain studies and suggest that chronic craniofacial pain in TMD patients may be associated with a dysfunction of the trigeminal nociceptive system.
Adult↗
Reduced habituation to experimental pain in migraine patients: a CO(2) laser evoked potential study.
The habituation to sensory stimuli of different modalities is reduced in migraine patients. However, the habituation to pain has never been evaluated. Our aim was to assess the nociceptive pathway function and the habituation to experimental pain in patients with migraine. Scalp potentials were evoked by CO(2) laser stimulation (laser evoked potentials, LEPs) of the hand and facial skin in 24 patients with migraine without aura (MO), 19 patients with chronic tension-type headache (CTTH), and 28 control subjects (CS). The habituation was studied by measuring the changes of LEP amplitudes across three consecutive repetitions of 30 trials each (the repetitions lasted 5 min and were separated by 5-min intervals). The slope of the regression line between LEP amplitude and number of repetitions was taken as an index of habituation. The LEPs consisted of middle-latency, low-amplitude responses (N1, contralateral temporal region, and P1, frontal region) followed by a late, high-amplitude, negative-positive complex (N2/P2, vertex). The latency and amplitude of these responses were similar in both patients and controls. While CS and CTTH patients showed a significant habituation of the N2/P2 response, in MO patients this LEP component did not develop any habituation at all after face stimulation and showed a significantly lower habituation than in CS after hand stimulation. The habituation index of the vertex N2/P2 complex exceeded the normal limits in 13 out of the 24 MO patients and in none of the 19 CTTH patients (P<0.0001; Fisher's exact test). Moreover, while the N1-P1 amplitude showed a significant habituation in CS after hand stimulation, it did not change across repetitions in MO patients. In conclusion, no functional impairment of the nociceptive pathways, including the trigeminal pathways, was found in either MO or CTTH patients. But patients with migraine had a reduced habituation, which probably reflects an abnormal excitability of the cortical areas involved in pain processing.
Adult↗
Representation of different trigeminal divisions within the primary and secondary human somatosensory cortex.
Clinical, neurophysiological, and neuroimaging studies have yielded controversial results about the representation of the face in the somatosensory cortex. To clarify this issue we mechanically stimulated the left forehead (ophthalmic trigeminal division, V1) and left lower lip (mandibular trigeminal division, V3) in 14 healthy volunteers during acquisition of whole-brain fMRI images. During V1 and V3 stimulation the fMRI signal in the primary (SI) and secondary (SII) somatosensory cortices in the contralateral hemisphere increased. Within both SI and SII, the foci activated by stimulation of the two trigeminal divisions largely overlapped. In contrast, the ipsilateral representation differed. Whereas V3 stimulation activated the contralateral somatosensory cortex alone, V1 stimulation activated SI and SII bilaterally. These results to some extent contrast with electrophysiological data in monkeys and disclose distinct cortical representations within facial territories in humans.
Adult↗
Is Ross syndrome a dysautonomic disorder only? An electrophysiologic and histologic study.
OBJECTIVE: To define the involvement of peripheral nerve fibers in Ross syndrome. METHODS: Mechanical pain perception, tactile and thermal thresholds on hand, foot dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV, H-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs), perioral, hand CO(2) laser late (LEPs) and ultralate evoked potentials, sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint, histamine, photopletysmographic and pupil pilocarpine tests, cutaneous innervation immunohistochemical techniques were studied in 3 patients with Ross syndrome. RESULTS: Quantitative sensory testing showed altered results in patients 1 and 2, and patient 3 had a slight impairment of mechanical pain perception. Nerve conduction, except for a median nerve distal reduction of sensory conduction in patient 1, F-wave and SSEP findings were normal; H-reflex was absent at rest in all patients. Hand LEPs were absent in patient 2, ultralate potentials were absent in patients 1 and 2. Skin biopsy showed a disease duration related reduction of unmyelinated and myelinated sensory fibers and a lack of unmyelinated autonomic fibers in all patients. CONCLUSIONS: Our data suggest that Ross syndrome is a degenerative disorder involving progressive sudomotor fibers, and then epidermal sensory unmyelinated and myelinated fibers.
Adult↗
Laser-evoked potentials in post-herpetic neuralgia.
OBJECTIVE: We evaluated the reliability of laser-evoked potentials (LEPs) as a diagnostic tool in patients with post-herpetic neuralgia (PHN), i.e. a chronic painful condition that causes small-diameter fibre dysfunction. Furthermore, we sought information on pathophysiology of PHN pain. METHODS: We recorded 'late' LEPs after stimulation of the supraorbital, upper cervical, lower cervical, upper thoracic, mid thoracic, and lower thoracic territories in 12 control subjects and 40 patients with PHN. We also determined the correlation of LEP data with age, duration of disease, and severity and quality of pain. RESULTS: At all stimulation sites, laser pulses invariably evoked high-amplitude brain potentials related to small-myelinated (A-delta) fibre activation. The laser perceptive threshold and LEP latency correlated with the distance of the dermatome from the brain (P<0.001). In patients, the perceptive threshold was higher and the LEP amplitude was lower in the affected dermatome than on the contralateral side (P<0.001). We found no significant LEP-clinical correlation except for a correlation between LEP abnormality and age. CONCLUSIONS: Being sensitive and reliable in assessing sensory function also in proximal dermatomes, LEPs are a promising diagnostic tool in radiculopathies. Although PHN severely impairs small myelinated fibres, the lack of a significant correlation between LEP abnormalities and pain suggests that pain in PHN does not chiefly arise from a dysfunction of small-myelinated afferents.
Adult↗
Evidence of a specific spinal pathway for the sense of warmth in humans.
While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting Adelta nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO(2)-laser pulses to the skin overlying the vertebral spinous processes. Using brain source analysis of the evoked responses with high-resolution electroencephalography and a realistic model of the head based on individual magnetic resonance imaging scans, we also studied the cortical areas involved in the cerebral processing of warm and nociceptive inputs. The activation of C warmth receptors evoked cerebral potentials with a main positive component peaking at 470-540 ms, i.e., a latency clearly longer than that of the corresponding wave yielded by Adelta nociceptive input (290-320 ms). Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the Adelta input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slow-conducting second-order neurons specific for the sense of warmth.
Adult↗
Nociceptive quality of the laser-evoked blink reflex in humans.
Laser radiant-heat pulses selectively excite the free nerve endings in the superficial layers of the skin and activate mechano-thermal nociceptive afferents; when directed to the perioral or supraorbital skin, high-intensity laser pulses evoke a blink-like response in the orbicularis oculi muscle (the laser blink reflex, LBR). We investigated the functional properties (startle or nociceptive origin) of the LBR and sought to characterize its central pathways. Using high-intensity CO(2)-laser stimulation of the perioral or supraorbital regions and electromyographic (EMG) recordings from the orbicularis oculi muscles, we did five experiments in 20 healthy volunteers. First, to investigate whether the LBR is a startle response, we studied its habituation to expected rhythmic stimuli and to unexpected arrhythmic stimuli. To assess its possible nociceptive quality, we studied changes in the LBR and the R2 component of the electrical blink reflex after a lidocaine-induced supraorbital nerve block and after intramuscular injection of the opiate fentanyl and the opiate-antagonist naloxone. To characterize the central pathways for the LBR, we investigated the interaction between the LBR and the three components of the blink reflex (R1, R2, and R3) by delivering laser pulses to the perioral or supraorbital regions before or after electrical stimulation of the supraorbital nerve at various interstimulus intervals. Finally, to gain further information on the central LBR pathways, using two identical CO(2)-laser stimulators, we studied the LBR recovery curves with paired laser pulses delivered to adjacent forehead points at interstimulus intervals from 250 ms to 1.5 s. The LBR withstood relatively high-frequency rhythmic stimulations, and unexpected laser pulses failed to evoke larger responses. When lidocaine began to induce hypoalgesia (about 5 min after the injection), the LBR was abolished, whereas R2 was only partly suppressed 10 min after the injection. Fentanyl injection induced strong, naloxone-reversible, LBR suppression (the response decreased to 25.3% of predrug values at 10 min and to 4% at 20 min), whereas R2 remained appreciably unchanged. Whether directed to the perioral or supraorbital regions, preceding laser pulses strongly suppressed R2 and R3 though not R1. Conversely, preceding electrical stimuli to the supraorbital nerve suppressed the LBR. In response to paired stimuli, the LBR recovered significantly faster than R2. These findings indicate that the LBR is a nociceptive reflex, which shares part of the interneuron chain mediating the nonnociceptive R2 blink reflex, probably in the medullary reticular formation. The LBR may prove useful for studying the pathophysiology of orofacial pain syndromes.
Adult↗
Small-fiber dysfunction in trigeminal neuralgia: carbamazepine effect on laser-evoked potentials.
BACKGROUND: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information on small-afferent (nociceptive) function. METHODS: The brain potentials evoked by CO(2)-laser pulses directed to the perioral and supraorbital regions were studied in 67 patients with idiopathic or symptomatic trigeminal neuralgia and 30 normal subjects. Of the 67 patients, 49 were receiving carbamazepine. RESULTS: All patients with symptomatic and 51% of those with idiopathic trigeminal neuralgia had frankly abnormal LEP on the painful side. The mean latency was significantly higher and mean amplitude lower on the painful than the nonpainful side. However, even on the nonpainful side, the mean latency was significantly longer than that of the age-matched controls. The nonpainful-side latency correlated significantly with the carbamazepine dose. CONCLUSIONS: LEP detect severe impairment of the nociceptive afferent system on the painful side of patients with idiopathic as well as symptomatic trigeminal neuralgia. A dysfunction of small-myelinated afferents may play an important role in the pathophysiology of neuralgic pain. Carbamazepine markedly dampens these brain potentials. The authors propose that this effect may result from inhibition of nociceptive transmission in the cingulate gyrus.
Afferent Pathways↗
Excitability of the human trigeminal motoneuronal pool and interactions with other brainstem reflex pathways.
We studied the properties of motoneurones and Ia-motoneuronal connections in the human trigeminal system, and their functional interactions with other brainstem reflex pathways mediated by non-muscular (Abeta) afferents. With surface EMG recordings we tested the recovery cycles of the heteronymous H-reflex in the temporalis muscle and the homonymous silent period in the masseter muscle both elicited by stimulation of the masseteric nerve at the infratemporal fossa in nine healthy subjects. In four subjects single motor-unit responses were recorded from the temporalis muscle. In six subjects we also tested the effect of the stimulus to the mental nerve on the temporalis H-reflex and, conversely, the effect of Ia input (stimulus to the masseteric nerve) on the R1 component of the blink reflex in the orbicularis oculi muscle. The recovery cycle of the H-reflex showed a suppression peaking at the 5-20 ms interval; conversely the time course of the masseteric silent period was facilitated at comparable intervals. The inhibition of the test H-reflex was inversely related to the level of background voluntary contraction. Single motor units were unable to fire consistently in response to the test stimulus at intervals shorter than 50 ms. Mental nerve stimulation strongly depressed the H-reflex. The time course of this inhibition coincided with the EMG inhibition elicited by mental nerve stimulation during voluntary contraction. The trigeminal Ia input facilitated the R1 component of the blink reflex when the supraorbital test stimulation preceded the masseteric conditioning stimulation by 2 ms. We conclude that the time course of the recovery cycle of the heteronymous H-reflex in the temporalis muscle reflects the after-hyperpolarization potential (AHP) of trigeminal motoneurones, and that the Ia trigeminal input is integrated with other brainstem reflexes.
Adult↗
Diazepam effects on the cerebral responses to tonic pain: a SPET study.
RATIONALE: Pain is a complex phenomenon with a strong affective-emotional component in addition to a sensory-discriminative one. This causes the activation of multiple brain areas, which process different aspects of pain simultaneously. OBJECTIVES: We investigated the effects of diazepam (DZ) on a well-known pattern of brain regions activated by cold, tonic pain stimuli. METHODS: Quantitative cerebral blood flow (CBF) was assessed by single photon emission tomography (SPET) and the Xe-133 inhalatory method, at rest and during tonic pain activation in eight normal, right-handed, male volunteers. The cold pressor test (CPT) was performed by immersion of the left hand in cold water twice, first during CPT alone, and again 30 min after intravenous administration of diazepam (CPT+DZ). RESULTS: During CPT we observed a significant CBF increase in the right thalamus, primary sensory-motor cortex (S1/M1), frontal and temporal regions, and in the left temporal region and anterior cingulate cortex (ACC). During CPT+DZ, the average CBF was significantly lower than during the CPT state (-11%, P<0.05). After normalisation, during CPT+DZ we again observed a significant CBF increase in the right thalamus, S1/M1 and frontal regions, and in the left ACC, though not in the temporal regions. DZ administration first causes a global reduction in CBF, then modifies the pattern of brain activation. CONCLUSIONS: During CPT, activation of the temporal regions has been interpreted as part of the affective-emotional component of pain response. DZ seems to affect the "pain-related" pattern of activation by abolishing the CBF increase in the temporal regions, without, however, modifying the pain perception or determining a sedating effect.
Adult↗
The problem of conduction velocity of the human spinothalamic tract.
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Animals↗
Head extensor reflex evoked by trigeminal stimulation in humans.
OBJECTIVE: Excitatory and inhibitory responses have been recognized in human cervical muscles following trigeminal stimulation. However, no evidence has so far been published of a crossed, short-latency, excitatory response resembling the early head extensor reflex seen in the cat. We seek its existence in humans. METHODS: The study was carried out in 14 voluntary healthy subjects. Percutaneous and surface electrical stimulation of the supraorbital and infraorbital nerves was performed with single, double and repetitive stimuli. Signals were recorded from the relaxed splenius and sternomastoid muscles bilaterally. RESULTS: Percutaneous stimulation of infraorbital nerve with single stimuli evoked an early response in the contralateral splenius muscle, with onset latency ranging from 11 to 14 ms (HR1). This response was greatly facilitated by double or repetitive stimuli. Single stimuli also gave rise to two larger responses in all 4 muscles in the latency ranges 50-70 ms (HR2) and 100-160 ms (HR3). Surface stimulation of one nerve alone could not elicit any early activity. Single surface stimuli delivered simultaneously to the supraorbital and infraorbital nerves evoked HR1 in only 5 subjects. CONCLUSIONS: We detected a crossed early reflex of the head extensor muscles to trigeminal stimuli. Its timing is similar to the 8-ms response seen in cats. The evidence provided suggests that the reflex is mediated by an oligosynaptic circuit and that it needs a strong spatial summation at central synapses.
Adult↗
Bladder filling inhibits somatic spinal motoneurones.
OBJECTIVES: Despite evidence that the activation of visceral afferents modulates spinal motoneurone activity in humans the responsible circuits remain unclear. We investigated changes in spinal motoneurone excitability during bladder filling in 8 healthy subjects and in 8 patients with spinal cord lesions and 5 patients with multi-infarct encephalopathy. METHODS: Spinal motoneurone excitability was studied by analysing changes in H-reflex, F-wave and motor-evoked potential (MEP) size recorded from the calf muscles under different bladder filling conditions. RESULT: In normal subjects, maximal bladder filling significantly suppressed the H-reflex, F-wave and MEPs; after bladder voiding these responses returned to normal. In patients with encephalopathy maximal bladder filling strongly reduced H-reflex size; similarly to normal subjects H-reflex returned to control value after bladder voiding. In patients with spinal cord lesions, activation of bladder afferents left the H-reflex unchanged. CONCLUSIONS: These findings indicate that bladder distension induces post-synaptic inhibition of spinal motoneurones through a suprasegmental pathway, which is interrupted by rostral spinal cord lesions. This vesical-induced inhibition is probably mediated by the propriospinal system rather than by the diffuse noxious inhibitory control circuit.
Adult↗