Giuseppe Libro

Reduced habituation to experimental pain in migraine patients: a CO2 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 CO2 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; Fishers 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.

Abnormal brain processing of cutaneous pain in patients with chronic migraine.

&NA; Syndromes with chronic daily headache include chronic migraine (CM). The reason for the transformation of migraine into chronic daily headache is still unknown. In this study, we aimed to evaluate heat pain thresholds and event‐related potentials following CO2‐laser thermal stimulation (LEPS) in hand and facial regions in patients with CM, to show changes in nociceptive brain responses related to dysfunction of pain elaboration at the cortical level. The results were compared with findings from normal control subjects and from subjects who suffer from migraine without aura. The effects of stimulus intensity, subjective pain perception and attention were monitored and compared with features of the LEPS. Twenty‐five CM patients, 15 subjects suffering from migraine without aura and 15 normal control subjects were enrolled in the study. LEPS amplitude variation was reduced in CM patients with respect to the perceived stimulus intensity, in comparison with migraine without aura patients and control subjects. In both headache groups, the distraction from the painful laser stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in comparison with control subjects. These results suggest an abnormal cortical processing of nociceptive input in CM patients, which could lead to the chronic state of pain. In both headache groups, an inability to reduce pain elaboration during an alternative cognitive task emerged as an abnormal behaviour probably predisposing to migraine.

Abnormal brain processing of cutaneous pain in migraine patients during the attack.

We examined cutaneous pain thresholds using CO(2) laser stimuli during migraine attacks, and defined the evoked cortical potential characteristics. Ten patients without aura were studied during attacks and for at least 72 h subsequently. Pain stimuli were generated on the dorsum of both hands and the right and left supraorbital zones, using pulses from a CO(2) laser. Absolute latencies of scalp potentials were measured at the highest peak of each response component, and the peak-to-peak amplitudes of N2a-P2 components were recorded. Cutaneous pain thresholds were significantly reduced on both the symptomatic and non-symptomatic sides during the attack, in comparison with the headache-free phase. The N2a-P2 complexes also increased in amplitude during attacks in comparison with the pain-free side. Thus, cutaneous hyperalgesia occurs during migraine attack, and is subtended by central sensitization phenomena, probably involving the cortex.

Habituation of single CO2 laser–evoked responses during interictal phase of migraine

A reduced habituation of averaged laser–evoked potential (LEP) amplitudes was previously found in migraine patients. The aim of the present study was to assess the habituation of single LEP responses and pain sensation during the interictal phase in migraine patients. Fourteen migraine patients were compared with ten control subjects. The pain stimulus was laser pulses, generated by CO2 laser, delivered to right supraorbital zone. Patients were evaluated during attack–free conditions. The LEP habituation was studied by measuring the changes of LEP amplitudes across and within three consecutive repetitions of 21 non–averaged trials. In migraine patients the N2–P2 wave amplitudes did not show a tendency toward habituation across and, above all, within the three repetitions. Anomalous behaviour of nociceptive cortex during the interictal phase of migraine may predispose patients to headache occurrence and persistence.

Changes in Cortical Processing of Pain in Chronic Migraine

Objective.—The aim of this study was to perform a topographic and dipolar analysis of nociceptive‐evoked responses obtained by laser stimulus under basal conditions in a cohort of chronic migraine (CM) patients, compared with migraine without aura (MWA) patients and noncraniofacial pain controls.

Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex

Abstract The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.

Zolmitriptan reverses blink reflex changes induced during the migraine attack in humans.

The question about the 5-hydroxytryptamine (5-HT)(1B-1D) receptors agonists, if the clinical efficacy in migraine attacks is linked with the action at the central level or at the peripheral one, is still unresolved. We evaluated the effects of zolmitriptan and sumatriptan on blink reflex in thirty migraine without aura patients during the attacks in order to assess the central action on the trigeminal system. Both drugs were effective in reducing headache severity compared to placebo. In the migraine attack an increased area of the R3 component on the pain side was observed; it was suppressed by zolmitriptan, which confirmed its action on the central trigeminal circuits, though the clinical relevance of this effect could be questioned.

Topographic and dipolar analysis of laser-evoked potentials during migraine attack.

Objective.—The aim of this study was to perform further evaluation of laser‐evoked potentials (LEPs) during migraine attacks using multichannel recording and topographic analysis. Specifically, this study aimed to confirm the pattern previously observed in acute migraine, while also defining the components of LEPs that are mainly modified during headache, as well as the correlation between features of LEPs and clinical variables. In addition, we aimed to conduct a dipolar source analysis of the main LEP waves in migraine patients to check the variability in the source location of LEPs during acute migraine.

Effects of remote cutaneous pain on trigeminal laser-evoked potentials in migraine patients

The present study aimed to evaluate heat pain thresholds and evoked potentials following CO2 laser thermal stimulation (laser-evoked potentials, LEPs), during remote application of capsaicin, in migraine patients vs. non-migraine healthy controls. Twelve outpatients suffering from migraine without aura were compared with 10 healthy controls. The LEPs were recorded by 6 scalp electrodes, stimulating the dorsum of the right hand and the right supraorbital zone in basal condition, during the application of 3% capsaicin on the dorsum of the left hand and after capsaicin removal. In normal subjects, the laser pain and the N2-P2 vertex complex obtained by the hand and face stimulation were significantly reduced during remote capsaicin application, with respect to pre-and post-capsaicin conditions, while in migraine LEPs and laser pain were not significantly modified during remote painful stimulation. In migraine a defective brainstem inhibiting control may coexist with cognitive factors of focalised attention to facial pain, less sensitive to distraction by a second pain.

Nitroglycerin induces migraine headache and central sensitization phenomena in patients with migraine without aura: a study of laser evoked potentials

In migraineurs nitroglycerin (NTG) induces severe delayed headache, resembling spontaneous migraine attacks. The aim of the present study was to evaluate NTG laser evoked potentials (LEP) features amplitude and pain sensation to laser stimuli during NTG-induced headache. Nine patients were selected. Headache was induced by oral administration of 0.6 mg of NTG; signals were recorded through disk electrodes placed at the vertex and referred to linked earlobes. CO(2)-LEPs delivered by stimulation of the dorsum of both hands and the right and left supraorbital zones were evaluated after the onset of moderate or severe headache resembling spontaneous migraine and at least 72 h after the end of the headache phase. Patients exhibited a significant heat pain threshold reduction and an LEPs amplitude increment during headache when both the supraorbital zones were stimulated. NTG appeared to support a reliable experimental model of migraine, based on the neuronal effects on the integrative-nociceptive structures. The LEPs facilitation during NTG-induced headache may be subtended by a hyperactivity of nociceptive cortex as well as by a failure of pain-inhibitory control.