Topiramate modulates habituation in migraine: evidences from nociceptive responses elicited by laser evoked potentials

Clemente, Laura Di; Puledda, Francesca; Biasiotta, A.; Viganò, Alessandro; Vicenzini, Edoardo; Truini, Andrea; Cruccu, G.; Piero, Vittorio Di

doi:10.1186/1129-2377-14-25

Cited by 31 publications

(45 citation statements)

References 35 publications

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“…In another study we had found similar electrophysiological abnormalities in healthy volunteers with a familial history of migraine, although they did not have any headache themselves at the time of the recordings [37]. A recent publication found that topiramate [38], one of the most effective drugs in migraine prevention, was able to normalize habituation in these patients. At baseline, episodic migraineurs showed a significant lack of habituation, which disappeared after 2 months of treatment with topiramate, and the individual improvement of habituation was positively correlated with the clinical benefit.…”

Section: Discussionmentioning

confidence: 75%

Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine

et al. 2013

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BackgroundPreventive pharmacotherapy for migraine is not satisfactory because of the low efficacy/tolerability ratio of many available drugs. Novel and more efficient preventive strategies are therefore warranted. Abnormal excitability of cortical areas appears to play a pivotal role in migraine pathophysiology. Transcranial direct current stimulation (tDCS) is a non-invasive and safe technique that is able to durably modulate the activity of the underlying cerebral cortex, and is being tested in various medical indications. The results of small open studies using tDCS in migraine prophylaxis are conflicting, possibly because the optimal stimulation settings and the brain targets were not well chosen. We have previously shown that the cerebral cortex, especially the visual cortex, is hyperresponsive in migraine patients between attacks and provided evidence from evoked potential studies that this is due to a decreased cortical preactivation level. If one accepts this concept, anodal tDCS over the visual cortex may have therapeutic potentials in migraine prevention, as it is able to increase neuronal firing.ObjectiveTo study the effects of anodal tDCS on visual cortex activity in healthy volunteers (HV) and episodic migraine without aura patients (MoA), and its potentials for migraine prevention.MethodsWe recorded pattern-reversal visual evoked potentials (VEP) before and after a 15-min session of anodal tDCS over the visual cortex in 11 HV and 13 MoA interictally. Then 10 MoA patients reporting at least 4 attacks/month subsequently participated in a therapeutic study, and received 2 similar sessions of tDCS per week for 8 weeks as migraine preventive therapy.ResultsIn HV as well as in MoA, anodal tDCS transiently increased habituation of the VEP N1P1 component. VEP amplitudes were not modified by tDCS. Preventive treatment with anodal tDCS turned out to be beneficial in MoA: migraine attack frequency, migraine days, attack duration and acute medication intake significantly decreased during the treatment period compared to pre-treatment baseline (all p < 0.05), and this benefit persisted on average 4.8 weeks after the end of tDCS.ConclusionsAnodal tDCS over the visual cortex is thus able to increase habituation to repetitive visual stimuli in healthy volunteers and in episodic migraineurs, who on average lack habituation interictally. Moreover, 2 weekly sessions of anodal tDCS had a significant preventive anti- migraine effect, proofing the concept that the low preactivation level of the visual cortex in migraine patients can be corrected by an activating neurostimulation. The therapeutic results indicate that a larger sham-controlled trial using the same tDCS protocol is worthwhile.

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Section: Discussionmentioning

confidence: 75%

Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine

et al. 2013

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“…Animal studies demonstrated that antiepileptic drugs with proven effects on CM, could modulate nociceptive transmission and central sensitization phenomena [26]. Neurophysiological studies based on cortical re- sponses to nociceptive stimuli confirmed that topiramate as well as OBT-A could modulate reduced habituation to painful inputs, which may be the neurophysiological sign of central sensitization [7,27]. Unfortunately, the present patient group was not so numerous to permit the evaluation of the subgroups treated with amitriptyline and topiramate, who could ideally show a greater improvement of allodynia.…”

Section: Obt-a Has Effect On Allodyniamentioning

confidence: 95%

Effects of Botulinum Toxin A on Allodynia in Chronic Migraine: An Observational Open-Label Two-Year Study

Tommaso¹,

Brighina²,

Delussi³

2019

Eur Neurol

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Background: Onabotulinumtoxin A (OBT-A) is a treatment option for chronic migraine (CM), though the possible effect on central sensitization and allodynia is still unknown. Aims: The present study aimed to evaluate (1) the long-term outcome of allodynia in a group of CM treated with OBT-A (2) if the presence and severity of allodynia could predict the long-term effect of OBT-A (3) if the improvement of allodynia, could contribute to the clinical efficacy of OBT-A. Methods: This was an observational, open-label, cohort study conducted on 99 CM patients treated for 1 year and 44 patients treated for 2 years with periodic OBT-A 155–195 U injections. In basal condition (T0), after 1 year (T1) and 2 years (T2) treatment, allodynia, migraine disability, and headache frequency were the main variables. Anxiety, depression and sleep deprivation were also considered potentially correlated factors to allodynia. Results: Allodynia decreased after 1 year (Student t test p = 0.0001), and decreased further after the second year of treatment (p = 0.015). There was a relationship between allodynia severity at T0 and reduced headache frequency change at T1 (r = 0.22) and T2 (r = 0.37). The effect of OBT-A on allodynia correlated with the reduction of MIDAS score after 1 year (r = 0.4) and 2 years (r = 0. 63) of treatment. Conclusions: OBT-A seems to have an effect on central sensitization, expressed by allodynia. This action could be exerted by modulating nociceptive transmission, and reducing the global burden of migraine. Patients with more severe allodynia display a limited long-term effect on headache frequency. The modulation of central sensitization could reduce migraine disability, in spite of the persistence of frequent headache.

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“…In episodic migraine the late component of laser evoked potentials (LEPs), mainly generated in the insular and anterior cingulate cortices, elicited by either cephalic (usually supraorbital) or extracephalic (usually hand dorsum) stimulation does not habituate during stimulus repetitions over short [65] or long durations [66-68]. Deficient habituation was also observed for the early N1 LEP component, mainly generated in the secondary somatosensory cortex [66,69]. In two studies performed in episodic migraine between attacks using contact-heat evoked potentials (CHEPS) and source localization with standardized LORETA (sLORETA) mapping it was shown that the lack of habituation to the noxious heat stimuli is probably related to the inability of the orbitofrontal cortex (OFC) to filter out correctly the pain information [70,71].…”

Section: Reviewmentioning

confidence: 99%

Habituation and sensitization in primary headaches

et al. 2013

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The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it’s cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary headaches paves the way for novel therapeutic targets and may allow a better understanding of the mode of action of available therapies.

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Topiramate modulates habituation in migraine: evidences from nociceptive responses elicited by laser evoked potentials

Cited by 31 publications

References 35 publications

Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine

Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine

Effects of Botulinum Toxin A on Allodynia in Chronic Migraine: An Observational Open-Label Two-Year Study

Habituation and sensitization in primary headaches

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