Effect of non-invasive vagus nerve stimulation on resting-state electroencephalography and laser-evoked potentials in migraine patients : mechanistic insights

A recent multicenter trial provided Class I evidence that for patients with an episodic migraine, non-invasive vagus nerve stimulation (nVNS) significantly increases the probability of having mild pain or being pain-free 2 h post-stimulation. Here we aimed to investigate the potential effect of nVNS in the modulation of spontaneous and pain related bioelectrical activity in a subgroup of migraine patients enrolled in the PRESTO trial by using resting-state electroencephalography and trigeminal laser-evoked potentials (LEPs). LEPs were recorded for 27 migraine patients who received active or sham nVNS over the cervical vagus nerve. We measured power values for frequencies between 1–100 Hz in a resting-state condition and the latency and amplitude of N1, N2, and P2 components of LEPs in a basal condition during and after active or sham vagus nerve stimulation (T0, T1, T2). The P2 evoked by the right and the left trigeminal branch was smaller during active nVNS. The sham device also attenuated the P2 amplitude evoked by the left trigeminal branch at T1 and T2, but this attenuation did not reach significance. No changes were observed for N1 amplitude, N1, N2, P2 latency, or pain rating. nVNS induced an increase of EEG power in both slow and fast rhythms, but this effect was not significant as compared to the sham device. These findings suggest that nVNS acts on the cortical areas that are responsible for trigeminal pain control and pave the ground for future studies aimed at confirming the possible correlations with clinical outcomes, including the effect on symptoms that are directly correlated with trigeminal pain processing and modulation

Traumatic experiences, stressful events, and alexithymia in chronic migraine with medication overuse

Background: Many factors are involved in the prognosis and outcome of Chronic Migraine and Medication Overuse Headache (CM+MOH), and their understanding is a topic of interest. It is well known that CM+MOH patients experience increased psychiatric comorbidity, such as anxiety, depression, or personality disorders. Other psychological factors still need to be explored. The present study is aimed to evaluate whether early life traumatic experiences, stressful life events, and alexithymia can be associated with CM+MOH. Methods: Three hundred and thirty-one individuals were recruited for this study. They belonged to one of the two following groups: CM+MOH (N = 179; 79% females, Age: 45.2 \ub1 9.8) and episodic migraine (EM) (N = 152; 81% females; Age: 40.7 \ub1 11.0). Diagnosis was operationally defined according to the International Classification of Headache Disorders 3rd edition (ICHD-III\u3b2). Data on early life (physical and emotional) traumatic experiences, recent stressful events and alexithymia were collected by means of the Childhood Trauma Questionnaire, the Stressful life-events Questionnaire, and the Toronto Alexithymia Scale (TAS-20), respectively. Results: Data showed a higher prevalence of emotional (\u3c72= 6.99; d.f. = 1; p = 0.006) and physical (\u3c72= 6.18; d.f. = 1; p = 0.009) childhood trauma and of current stressful events of important impact (\u3c72= 4.42; d.f. = 1; p = 0.025) in CM+MOH patients than in EM ones. CM+MOH patients were characterized by higher difficulties in a specific alexithymic trait (Factor 1 subscale of TAS-20) [F(1, 326)= 6.76, p = 0.01, \u3b7p2= 0.02] when compared to the EM group. The role of these factors was confirmed in a multivariate analysis, which showed an association of CM+MOH with emotional (OR 2.655; 95% CI 1.153-6.115, p = 0.022) or physical trauma (OR 2.763; 95% CI 1.322-5.771, p = 0.007), and a high score at the Factor 1 (OR 1.039; 95% CI 1.002-1.078, p = 0.040). Conclusions: Our findings demonstrated a clear relationship between CM+MOH and life traumas, stressful events, and alexithymia. These observations have a relevant role in multiple fields of related to chronic headache: from the management to the nosographic framing

Medication overuse headache, addiction and personality pathology: a controlled study by SWAP-200

Background: Medication Overuse Headache (MOH) is a type of chronic headache, whose mechanisms are still unknown. Some empirical investigations examining the addiction-like behaviors and processes, as well as personality characteristics underlying MOH development, reached contrasting findings. This study aimed at detecting personality and its disorders (PDs) in MOH patients, with a specific attention to the features of addiction. Methods: Eighty-eight MOH patients have been compared with two clinical populations including 99 patients with Substance Use Disorder (SUD) and 91 with PDs using the Shedler-Westen Assessment Procedure-200 (SWAP-200). MANCOVAs were performed to evaluate personality differences among MOH, SUD and PD groups, controlling for age and gender. Results: MOH patients showed lower traits of the SWAP-200’s clusters A and B disorders than SUD and PD patients, whom presented more severe levels of personality impairment. No differences in the SWAP-200’s cluster C have been found, indicating common personality features in these populations. At levels of specific PDs, MOH patients presented higher obsessive and dysphoric traits, as well as better overall psychological functioning than SUD and PD patients. Conclusions: The study supported the presence of a specific pattern of personality in MOH patients including obsessive (perfectionist) and dysphoric characteristics, as well as good enough psychological resources. No similarities with drug addicted and personality-disordered patients were found. Practitioners’ careful understanding of the personality of MOH patients may be useful to provide more effective treatment strategies and patient-tailored intervention programs

Focus on therapy of hypnic headache

Hypnic headache (HH) is a primary headache disorder, which occurs exclusively during sleep and usually begins after 50 years of age. There are no controlled trials for the treatment of HH. We reviewed all the available papers, including 119 cases published in literature up to date, reporting the efficacy of the medications used to treat HH. Acute treatment is not recommended, since no drug proved to be clearly effective and also because the intensity and the duration of the attacks do not require the intake of a medication in most cases. As for prevention, a wide variety of medications were reported to be of benefit in HH. The drugs that were found to be effective in at least five cases are: lithium, indomethacin, caffeine and flunarizine. Lithium was the most extensively studied compound and demonstrated to be an efficacious treatment in 32 cases. Unfortunately, despite its efficacy, significant adverse effects and poor tolerability are not rare, mainly in elderly patients. Many patients reported a good response to indomethacin, but some could not tolerate it. Caffeine and melatonin treatments did not yield robust evidence to recommend their use as single preventive agents. Nevertheless, their association with lithium or indomethacin seems to produce an additional therapeutic efficacy. A course of lithium should be tried first, followed 3–4 months later by tapering. If headache recurs during tapering, a longer duration of therapy may be needed. If lithium treatment does not provide a significant response, indomethacin can be commenced as second-line approach. If these treatments prove to be ineffective or poorly tolerated, other agents, such as caffeine and melatonin, can be administered

Non-invasive brain and spinal stimulation for pain and related symptoms in multiple sclerosis: a systematic review

Background: Neuropathic and nociceptive pain frequently affect patients with multiple sclerosis (MS), with a prevalence close to 90% and significant impact on general health and quality of life. Pharmacological strategies are widely used to treat pain in MS, but their effectiveness and side-effects are controversial. Among non-pharmacological treatments for pain, non-invasive brain and spinal stimulation (NIBSS) has shown promising preliminary results in MS.Objective: Systematic review to investigate the effect of NIBSS for the management of pain in MS.Methods: A literature search using Pubmed, Science Direct and Web of Science was conducted from databases inception to February 21, 2020 for studies assessing the analgesic effect of NIBSS on pain in MS.Results: A total of 279 records were title- and abstract-screened, nine were assessed for full text and included. The NIBSS techniques explored were transcranial direct current stimulation (N = 5), transcranial magnetic stimulation (N = 2), transcranial random noise stimulation (N =1), transcutaneous spinal direct current stimulation (N = 1). The targets were the primary motor cortex (M1; N = 4), the left dorsolateral pre-frontal cortex (DLPFC; N = 3), the spinal cord (N = 1), unspecified brain target (N = 1). The study designs were randomized (N = 7), open label (N = 1), single case report (N = 1). Despite the differences in study design, target and NIBSS technique that impeded a meta-analysis, all the studies converge in showing a significant improvement of pain after active NIBSS with less consistent effects on other symptoms of the pain-related cluster (depression, fatigue, cognition) and quality of life.Conclusions: Excitatory NIBSS over M1, left DLPFC and spinal cord appear to be the most effective protocols for pain in MS. Open questions include the use of neurophysiological or neuroimaging surrogate outcome measures, the stratification of patients according to the clinical profiles and underlying pathogenetic mechanisms and the combination of NIBSS to pharmacological treatment, neurorehabilitation, or psychotherapy to improve the clinical effect. The duration of the effect to NIBSS and the feasibility and efficacy of telemedicine NIBSS protocols are other open key questions

The endocannabinoid system in migraine: from bench to pharmacy and back.

PURPOSE OF REVIEW: Migraine is a common, highly disabling disorder. Its treatment involves acute and preventive therapy. Many of available preventive medications are not well tolerated, which results in poor compliance and limited effectiveness. Cannabinoids have been proposed for the treatment of migraine but their efficacy and tolerability are controversial. RECENT FINDINGS: Cannabinoids modulate functions and activity of signaling pathways that have a key role in pain control. Growing preclinical evidence and initial clinical findings suggest that modulation of the endocannabinoid system, via endogenous or exogenous cannabinoids may be relevant for migraine via multiple mechanisms. SUMMARY: The endocannabinoid system qualifies as an interesting area of research worth exploration in the quest for therapeutic targets for the treatment of migraine

Noninvasive vagus nerve stimulation as acute therapy for migraine. The randomized PRESTO study

Objective: To evaluate the efficacy, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS; gammaCore; electroCore, LLC, Basking Ridge, NJ) for the acute treatment of migraine in a multicenter, double-blind, randomized, sham-controlled trial. Methods: A total of 248 participants with episodic migraine with/without aura were randomized to receive nVNS or sham within 20 minutes from pain onset. Participants were to repeat treatment if pain had not improved in 15 minutes. Results: nVNS (n = 120) was superior to sham (n = 123) for pain freedom at 30 minutes (12.7% vs 4.2%; p = 0.012) and 60 minutes (21.0% vs 10.0%; p = 0.023) but not at 120 minutes (30.4% vs 19.7%; p = 0.067; primary endpoint; logistic regression) after the first treated attack. A post hoc repeatedmeasures test provided further insight into the therapeutic benefit of nVNS through 30, 60, and 120 minutes (odds ratio 2.3; 95% confidence interval 1.2, 4.4; p = 0.012). nVNS demonstrated benefits across other endpoints including pain relief at 120minutes and was safe and well-tolerated. Conclusion: This randomized sham-controlled trial supports the abortive efficacy of nVNS as early as 30 minutes and up to 60 minutes after an attack. Findings also suggest effective pain relief, tolerability, and practicality of nVNS for the acute treatment of episodic migraine

Electrical stimulation of injected muscles to boost botulinum toxin effect on spasticity: rationale, systematic review and state of the art

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms "electric stimulation", "muscle spasticity" and "botulinum toxins" and strings "electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A" was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake

Harassment in the headache field: a global web-based cross-sectional survey

Inequalities; Sexual harassment; WorkplaceDesigualdades; Acoso sexual; Lugar de trabajoDesigualtats; Assetjament sexual; Lloc de treballBackground Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. Methods We adopted a cross‑sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). Results Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5–13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0–2.0). Conclusions Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.This work was supported by a granted project proposal by the International Headache Society

FAAH inhibition as a preventive treatment for migraine: A pre-clinical study

Abstract Background Fatty-acid amide hydrolase (FAAH) is an intracellular serine hydrolase that catalyzes the cleavage of endogenous fatty-acid amides, including the endocannabinoid anandamide (AEA). We previously reported that the peripherally restricted FAAH inhibitor URB937, which selectively increases AEA levels outside the central nervous system, reduces hyperalgesia and c-Fos expression in the trigeminal nucleus caudalis (TNC) and the locus coeruleus in an animal model of migraine based on nitroglycerin (NTG) administration. Aim To further investigate the relevance of FAAH inhibition in the NTG animal model of migraine by testing the effects of the globally active FAAH inhibitor URB597. Methods Our experimental approach involved mapping neuronal c-Fos protein expression, measurement of AEA levels in brain areas and in trigeminal ganglia, evaluation of pain-related behavior and quantification of molecular mediators in rats that received URB597 (2 mg/kg i.p.) either before or after NTG administration (10 mg/kg, i.p.). Results Pre-treatment with URB597 significantly reduced c-Fos immunoreactivity in the TNC and inhibited NTG-induced hyperalgesia in the orofacial formalin test. This behavioral response was associated with a decrease in neuronal nitric oxide synthase, calcitonin gene-related peptide and cytokine gene expression levels in central and peripheral structures. Administration of URB597 after NTG had no such effect. Conclusions The findings suggest that global FAAH inhibition may offer a therapeutic approach to the prevention, but not the abortive treatment, of migraine attacks. Further studies are needed to elucidate the exact cellular and molecular mechanisms underlying the protective effects of FAAH inhibition