Michele Sardaro

Fibromyalgia Comorbidity in Primary Headaches

Fibromyalgia syndrome (FMS) is a chronic pain condition of unknown aetiology characterized by diffuse pain and tenderness at tender points. The aim of the study was to assess the prevalence and clinical features of FMS in the different forms of primary headaches, in a tertiary headache centre. Primary headache patients (n = 217) were selected and submitted to the Total Tenderness Score, anxiety and depression scales, Migraine Disability Assessment, allodynia questionnaire, Short Form 36 Health Survey and the Medical Outcomes Study-Sleep Scale. In patients with FMS, the Multidimensional Assessment of Fatigue, the Pain Visual Analog Scale, the Manual Tender Point Survey and the Fibromyalgia Impact Questionnaire were employed. FMS was present in 36.4% of patients and prevailed significantly in tension-type headache and in patients with higher headache frequency. Headache frequency, pericranial muscle tenderness, anxiety and sleep inadequacy were especially associated with FMS comorbidity. In the FMS patients, fatigue and pain at tender points were significantly correlated with headache frequency. FMS seems increasingly prevalent with increased headache frequency, for the facilitation of central sensitization phenomena favoured by anxiety and sleep disturbances.

Lack of habituation of nociceptive evoked responses and pain sensitivity during migraine attack

OBJECTIVE The aim of the present study was to investigate the habituation of subjective pain sensation to CO(2) laser stimulus, in relation to the amplitude modifications of the cortical evoked responses (LEPs), during both the migraine attack and the not symptomatic phase. METHODS Fourteen migraine patients were selected and compared with 10 healthy controls. Eight patients were evaluated during both the pain-free and the attack phases. Three following series of 20 averaged LEPs were recorded, stimulating the hands and the supraorbital zones: during the attack, two consecutive series of 20 averaged LEPs were carried out. The subjective sensation was requested for each laser stimulus, using a 0-10 points Verbal Rating Scale (VRS). RESULTS In normal subjects the N2-P2 waves amplitude showed habituation across the three repetitions, which correlated with the habituation of the subjective rating of the stimulus. During the not symptomatic phase, patients showed a lack of habituation of the N2-P2 amplitude when the hand and the face was stimulated, with a pattern of increase of the pain rating across the three repetitions; in addition there was a lack of correlation between the LEPs amplitude and the subjective sensation. During the attack, the LEPs amplitude and the pain rating were increased when the face was stimulated, but they did not habituate across the two repetitions, likely the pain-free condition. The percent LEPs amplitude variation across the three repetitions correlated with the main indices of migraine severity, mainly when the supraorbital zone was stimulated. CONCLUSIONS The abnormal cortical excitability in migraine could condition an anomalous behavior of nociceptive cortex during the interictal phase of migraine: it persists during the acute phase, and correlates with the frequency and duration of migraine. SIGNIFICANCE The reduced habituation of the nociceptive cortex may concur with the onset and evolution of headache.

Effects of the remote C fibres stimulation induced by capsaicin on the blink reflex in chronic migraine.

The aim of this study was to test the function of the diffuse noxious inhibitory control system (DNIC) in chronic and episodic migraine, exploring the blink reflex (BR) modifications induced by topical application of capsaicin on the hand. We evaluated 11 migraine without aura (MA) and nine chronic migraine (CM) patients during the not symptomatic phase; they were compared with 14 non-headache subjects (N). The BR was elicited by weak electrical stimuli delivered to the right supraorbital nerve; it was obtained 10 min and 20 min after the application of 1 ml of 3% capsaicin in a cream base (Teofarma) on the skin of the dorsum of the right hand, and 60 min after capsaicin removal. The subjective pain sensation induced by capsaicin was significantly increased in CM with respect to both MA patients and normal subjects; the R2 area was increased in CM patients during capsaicin application, with respect to controls and MA patients, who did not exhibit any reflex alterations. These results may suggest a failure of DNIC and a disturbed control of the trigeminal reflex at the central level, linked with migraine frequency.

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.

Influence of aesthetic perception on visual event-related potentials

The aim of the study was to assess the effects of visual aesthetic perception on event-related potentials (ERPs). Eight subjects assigned an aesthetic judgment (beautiful, neutral, or ugly) and a 10-step beauty estimation to the target stimuli, consisting of famous artistic pictures and geometric shapes. In a further task, the subjects performed a motor response to the previously judged pictures and geometric shapes. ERPs were recorded through 54 scalp electrodes during both tasks. The P3b amplitude was increased during the categorization of the geometric shapes compared to the artistic figures and during the vision of the beautiful targets preceding the motor response. The categorization of the aesthetic qualities of geometrical shapes seems to induce a higher level of attention, while a higher arousal variation was elicited by the recognition of beauty, in any form that was presented.

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.

Aesthetic value of paintings affects pain thresholds

Pain is modulated by cognitive factors, including attention and emotions. In this study we evaluated the distractive effect of aesthetic appreciation on subjectively rated pain (visual analogue scale;VAS) and multi-channel evoked potentials induced by CO(2) laser stimulation of the left hand in twelve healthy volunteers. Subjects were stimulated by laser in the absence of other external stimulation (baseline condition) and while looking at different paintings they had previously rated as beautiful, neutral or ugly. The view of paintings previously appreciated as beautiful produced lower pain scores and a clear inhibition of the P2 wave amplitude, localized in the anterior cingulate cortex; the inhibition of P2 wave amplitude was lesser or not significant during the presentation of the ugly or neutral paintings, respectively. Dipole source localization analysis of the LEP peaks showed significant changes during different conditions, with a shift from the posterior to the anterior right cingulated cortex while looking at paintings previously rated as beautiful. Our results provide evidence that pain may be modulated at cortical level by the aesthetic content of the distracting stimuli.

Pain perception and laser evoked potentials during menstrual cycle in migraine

The association between estrogens “withdrawal” and attacks of migraine without aura is well-known. The aim of the study was to examine the features of laser evoked potentials (LEPs), including habituation, in women suffering from migraine without aura versus healthy controls, during the pre-menstrual and late luteal phases. Nine migraine without aura and 10 non-migraine healthy women, were evaluated during the pre-menstrual phase and late luteal phase. The LEPs were recorded during the inter-critical phase. The right supraorbital zone and the dorsum of the right hand were stimulated. Three consecutive series of 20 laser stimuli were obtained for each stimulation site. Laser pain perception was rated by a 0–100 VAS after each stimulation series. Migraine patients exhibited increased LEPs amplitude and reduced habituation compared to normal subjects. Laser-pain perception was increased during the pre-menstrual phase in both patients and controls. Migraine patients and controls showed increased P2 and N2–P2 amplitude in the pre-menstrual phase, on both stimulation sites. During the pre-menstrual phase the N2–P2 habituation appeared to be reduced in both migraine and healthy women. The estrogen withdrawal occurring during the menstrual cycle may favor reduced habituation of nociceptive cortex, which may facilitate pain symptoms and migraine in predisposed women.

Effects of Distraction Versus Spatial Discrimination on Laser‐Evoked Potentials in Migraine

Objectives.— To evaluate whether migraine patients exhibit less inhibition to painful stimuli when distracted from pain as compared to healthy subjects, testing the spatial discrimination of painful stimuli, the performance during the mental arithmetic task used to contrast the discrimination performance and the behavior of N1 and N2‐P2 laser‐evoked potentials (LEPs) amplitudes during spatial discrimination and during distraction.

Effects of symptomatic treatments on cutaneous hyperalgesia and laser evoked potentials during migraine attack

Previously an amplitude enhancement of laser evoked potentials (LEPs) was detected during migraine attack: we further examined pain threshold to CO2 laser stimuli and LEPs during attacks, evaluating the effect of almotriptan, lysine-acetylsalicylate and placebo treatment on cutaneous hyperalgesia to thermal stimuli delivered by CO2 laser and on LEP components. Eighteen patients suffering from migraine without aura were analysed. They were divided into three groups of six patients each, randomly assigned to lysine acetyl-salicylate, almotriptan or placebo treatments. The supraorbital zones and the dorsum of the hand were stimulated on both the symptomatic and not symptomatic side in all patients. The LEPs were recorded by 25 scalp electrodes During attacks, the P2 wave was significantly enhanced; the amplitude of the P2 component obtained by the stimulation of the supraorbital zone during the attack on the side of the headache was significantly correlated with the intensity of pain and the frequency of headache. Both almotriptan and lysine acetyl-salicylate significantly reduced the P2 amplitude but they showed no effects on hyperalgesia to laser stimulation; headache relief following therapy was correlated with the reduction of the P2 amplitude. The cortical elaboration of laser-induced experimental pain seemed increased during migraine attack, and the severity of headache was mainly related to the increase of the later LEPs components expressing the attentive and emotive compounds of suffering. Reversion of this process appeared to be primarily responsible for the efficacy of drugs in treating migraine, though both almotriptan and lysine-acetil salicilate seemed to have no effect in reducing sensitization at second and third order nociceptive neurons.