Antiepileptic drugs in the treatment of headache: Neuroprotective effect or something else?

The hypothesis that cortical hyperexcitability may play an important role in the physiopathology of migraine has lead to the therapeutic use of antiepileptic drugs in headache prophylaxis. Cortical hyperexcitability is due to an imbalance between neuronal inhibition, mediated by gamma-aminobutyrric acid (GABA), and neuronal excitement, mediated by excitatory aminoacids. It becomes therefore clear how cortical excitability may be modulated by acting on mechanisms such as the synthesis and metabolism of GABA and on targets such as GABA and glutamate receptors and on sodium and calcium channels. The question is, whether, thanks to their tolerability and rapidity of action, these should be considered as first-choice prophylaxis drugs rather than simply as alternative drugs. Thanks to their action on the key-mechanisms implicated in the genesis and maintenance of pain, valproic acid, gabapentin, topiramate, levetiracetam and lamotrigine have all the requisites in terms of efficacy, tolerability and rapidity of action that are requested from a drug in order to be considered a firstchoice drug rather than simply an alternative to the drugs currently used. The expansion, however, of medical areas in which antiepileptic drugs are prescribed and the growing number of patients using them, require an increased sensitivization in order to avoid their incorrect use. © Springer-Verlag Italia 2004

<i>ZNRD1-AS</i> and <i>RP11-819C21.1</i> long non-coding RNA changes following painful laser stimulation correlate with laser-evoked potential amplitude and habituation in healthy subjects:A pilot study

Background Non-coding RNAs (lncRNAs) are a group of non-coding RNAs that act as regulators of gene expression; they are implicated in various human diseases and have been reported to be involved in the modulation of pain. We aimed to study whether: (a) lncRNAs modifications could be found in an experimental model of pain; (b) there was a correlation between lncRNA changes and laser evoked potential (LEP) amplitude/laser-pain rating. Methods Laser evoked potentials were recorded from 11 healthy subjects to both left hand and perioral region stimulation. Three consecutive averages were calculated for each stimulation site in order to investigate the LEP amplitude habituation. Blood samples were obtained immediately before LEP recording (pre-pain) and 30-min after the recording of the last LEP average (post-pain). Eighty-four lncRNAs, involved in autoimmunity and human inflammatory response, were screened. The criteria used for lncRNAs analysis were fold change &gt;2 and p &lt; .05. By Real-Time PCR, we identified two lncRNAs up-regulated at the post-pain time, as compared to the pre-pain time: RP11-819C21.1 (fold change = 8.2; p = .038) and ZNRD1 antisense RNA 1 non-protein coding (ZNRD1-AS; fold change = 6.3; p = .037). Results The ZNRD1-AS up-regulation was directly correlated with the N1 amplitude, while the RP11-819C21.1 increase after pain showed a correlation with the reduced N2/P2 amplitude and laser-pain habituation. Conclusion IncRNA changes in a human experimental phasic pain model. The correlation between lncRNA changes and LEP amplitude and habituation suggests that RP11-819C21.1 and ZNRD1-AS could be involved in the pathophysiology of painful diseases characterized by abnormal excitability of the cerebral cortex. Significance Long non-coding RNAs are upregulated after experimental pain. RP11-819C21.1 and ZNRD1 could be involved in the pathophysiology of diseases characterized by reduced habituation to pain

Abnormal Circadian Modification of A\u3b4-Fiber Pathway Excitability in Idiopathic Restless Legs Syndrome

Restless legs syndrome (RLS) is characterized by unpleasant sensations generally localized to legs, associated with an urge to move. A likely pathogenetic mechanism is a central dopaminergic dysfunction. The exact role of pain system is unclear. The purpose of the study was to investigate the nociceptive pathways in idiopathic RLS patients. We enrolled 11 patients (mean age 53.2\u2009\ub1\u200919.7 years; 7 men) suffering from severe, primary RLS. We recorded scalp laser-evoked potentials (LEPs) to stimulation of different sites (hands and feet) and during two different time conditions (daytime and nighttime). Finally, we compared the results with a matched control group of healthy subjects. The A\u3b4 responses obtained from patients did not differ from those recorded from control subjects. However, the N1 and the N2-P2 amplitudes' night/day ratios after foot stimulation were increased in patients, as compared to controls (N1: patients: 133.91\u2009\ub1\u200950.42%; controls: 83.74\u2009\ub1\u200934.45%; p = 0.016; A\u3b4-N2-P2: patients: 119.15\u2009\ub1\u200915.56%; controls: 88.42\u2009\ub1\u200923.41%; p = 0.003). These results suggest that RLS patients present circadian modifications in the pain system, which are not present in healthy controls. Both sensory-discriminative and affective-emotional components of pain experience show parallel changes. This study confirms the structural integrity of A\u3b4 nociceptive system in idiopathic RLS, but it also suggests that RLS patients present circadian modifications in the pain system. These findings could potentially help clinicians and contribute to identify new therapeutic approaches

Migraine, arousal and sleep deprivation: comment on: "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study"

We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli

Theory of Mind in migraine and medication-overuse headache: A cross-sectional study

Theory of Mind (ToM) is the ability to predict and anticipate others' behaviors through the mental state attribution process. This study aims to investigate the ToM in patients with medication-overuse headache (MOH) and episodic migraine (EM) and to compare it with healthy controls (HC)

Chronic paroxysmal hemicrania in paediatric age: report of two cases

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with hemicrania continua and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) as trigeminal autonomic cephalalgia (TACs). CPH is characterised by short-lasting (2–30 min), severe and multiple (more than 5/day) pain attacks. Headache is unilateral, and fronto-orbital-temporal pain is combined with cranial autonomic symptoms. According to the International Classification of Headache Disorders, 2nd edition, the attacks are absolutely responsive to indomethacin. CPH has been only rarely and incompletely described in the developmental age. Here, we describe two cases concerning a 7-year-old boy and a 11-year-old boy with short-lasting, recurrent headache combined with cranial autonomic features. Pain was described as excruciating, and was non-responsive to most traditional analgesic drugs. The clinical features of our children’s headache and the positive response to indomethacin led us to propose the diagnosis of CPH. Therefore, our children can be included amongst the very few cases of this trigeminal autonomic cephalgia described in the paediatric age

Antiepileptic drugs in the preventive treatment of migraine in children and adolescents

Migraine prevalence in childhood ranges from 2.7 to 10% causing a significant impact on quality of life. No drugs are currently approved for use in the prevention of pediatric migraine. Antiepileptic drugs such as valproate and topiramate have been approved for the preventive treatment of migraine in adults. The present study aimed at reviewing evidence on the efficacy and safety of antiepileptic drugs in the preventive treatment of migraine in children and adolescents. We searched PubMed from 1988 to May 2007 and reviewed, abstracted, and classified relevant literature. Thirteen studies were reviewed. Data from randomized controlled trials are available only for valproate and topiramate. They show that both topiramate and valproate are effective in reducing headache frequency, intensity, and duration. As for safety and tolerability, topiramate is well tolerated, while there are insufficient data regarding the tolerability of valproate. Open-label or retrospective studies suggest that levetiracetam, zonisamide, and gabapentin are effective, but further evidence is warranted to confirm these data. © 2007 Wiley-Liss, Inc

The contribution of clinical neurophysiology to the comprehension of the tension-type headache mechanisms

so far, clinical neurophysiological studies on tension-type headache (TTH) have been conducted with two main purposes: (1) to establish whether some neurophysiological parameters may act as markers of TTH, and (2) to investigate the physiopathology of TTH. with regard to the first point, the present results are disappointing, since some abnormalities found in TTH patients may be frequently observed also in migraineurs. on the other hand, clinical neurophysiology has played an important role in the debate about the pathogenesis of TTH. studies on the exteroceptive suppression of the temporalis muscle contraction have detected a dysfunction of the brainstem excitability and of its suprasegmental control. a similar conclusion has been reached by using the trigeminocervical reflexes, whose abnormalities in TTH have suggested a reduced inhibitory activity of brainstem interneurons, reflecting abnormal endogenous pain control mechanisms. It is interesting that the neural excitability abnormality in TTH seems to be a generalized phenomenon, not limited to the cranial districts. defective DNIC-like mechanisms have indeed been evidenced also in somatic districts by nociceptive flexion reflex studies. unfortunately, most neurophysiological studies on TTH are marred by serious methodological flaws, which should be avoided in future researches, in order to better clarify the TTH mechanisms. (C

Triptans other than sumatriptan in child and adolescent migraine:literature review

abortive drugs used for migraine in children and adolescents are usually the same as those used in adults. only a few studies have assessed the efficacy of triptans other than sumatriptan in pediatric migraine. this systematic review describes the evidence concerning the efficacy and tolerability of these triptans. the pubmed research produced 481 results and only seven studies were randomized controlled trials. a total of 11 articles were reviewed. zolmitriptan and rizatriptan were superior to placebo in most studies. almotriptan demonstrated a high profile of tolerability. a single study of eletriptan demonstrated no statistical difference between this drug and placebo in terms of both efficacy and tolerability. all studies have reported a good triptan safety profile. the conflicting data regarding triptan efficacy are probably due to differences in populations, methodologies and efficacy measures among the different studies. triptans are an important option in the symptomatic treatment of childhood and adolescent migraine