Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS):a randomized, monocentric clinical trial

Background Aim of the study was assessment of efficacy and safety of transcutaneous stimulation of the auricular branch of the vagal nerve (t-VNS) in the treatment of chronic migraine. Methods A monocentric, randomized, controlled, double-blind study was conducted. After one month of baseline, chronic migraine patients were randomized to receive 25 Hz or 1 Hz stimulation of the sensory vagal area at the left ear by a handhold battery driven stimulator for 4 h/day during 3 months. Headache days per 28 days were compared between baseline and the last month of treatment and the number of days with acute medication was recorded The Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires were used to assess headache-related disability. Results Of 46 randomized patients, 40 finished the study (per protocol). In the per protocol analysis, patients in the 1 Hz group had a significantly larger reduction in headache days per 28 days than patients in the 25 Hz group (−7.0 ± 4.6 vs. −3.3 ± 5.4 days, p = 0.035). 29.4 % of the patients in the 1 Hz group had a ≥50 % reduction in headache days vs. 13.3 % in the 25 Hz group. HIT-6 and MIDAS scores were significantly improved in both groups, without group differences. There were no serious treatment-related adverse events. Conclusion Treatment of chronic migraine by t-VNS at 1 Hz was safe and effective. The mean reduction of headache days after 12 weeks of treatment exceeded that reported for other nerve stimulating procedures

Injectivity of sections of convex harmonic mappings and convolution theorems

In the article the authors consider the class ${\mathcal H}_0$ of sense-preserving harmonic functions $f=h+\overline{g}$ defined in the unit disk $|z|<1$ and normalized so that $h(0)=0=h'(0)-1$ and $g(0)=0=g'(0)$, where $h$ and $g$ are analytic in the unit disk. In the first part of the article we present two classes $\mathcal{P}_H^0(\alpha)$ and $\mathcal{G}_H^0(\beta)$ of functions from ${\mathcal H}_0$ and show that if $f\in \mathcal{P}_H^0(\alpha)$ and $F\in\mathcal{G}_H^0(\beta)$, then the harmonic convolution is a univalent and close-to-convex harmonic function in the unit disk provided certain conditions for parameters $\alpha$ and $\beta$ are satisfied. In the second part we study the harmonic sections (partial sums) $$s_{n, n}(f)(z)=s_n(h)(z)+\overline{s_n(g)(z)},$$ where $f=h+\overline{g}\in {\mathcal H}_0$, $s_n(h)$ and $s_n(g)$ denote the $n$-th partial sums of $h$ and $g$, respectively. We prove, among others, that if $f=h+\overline{g}\in{\mathcal H}_0$ is a univalent harmonic convex mapping, then $s_{n, n}(f)$ is univalent and close-to-convex in the disk $|z|< 1/4$ for $n\geq 2$, and $s_{n, n}(f)$ is also convex in the disk $|z|< 1/4$ for $n\geq2$ and $n\neq 3$. Moreover, we show that the section $s_{3,3}(f)$ of $f\in {\mathcal C}_H^0$ is not convex in the disk $|z|<1/4$ but is shown to be convex in a smaller disk.Comment: 16 pages, 3 figures; To appear in Czechoslovak Mathematical Journa

Validation of the English Language Pain Sensitivity Questionnaire

Background and Objectives: The Pain Sensitivity Questionnaire (PSQ) is predictive of pain-related responses to experimental stimuli in German-speaking individuals. Here, we explored the validation of the English translation of the PSQ (PSQ-E). Methods: One hundred thirty-six patients scheduled to undergo a low back interventional procedure completed the PSQ-E and other questionnaires including the Brief Pain Inventory. Pain ratings on a visual analog scale (VAS) were obtained following 2 standardized injections of subcutaneous lidocaine (VAS 1, infiltration in hand; VAS 2, infiltration of procedural site). The VAS measures were compared with the PSQ-E data and other inventories using linear regression analysis with stepwise selection of variables. Results: The PSQ-E properties were in all respects similar to those of the original German PSQ. VAS 1 magnitude was predicted by PSQ-E-minor (r = 0.26, P < 0.01). VAS 2 magnitude was predicted by PSQ-E-minor (r = 0.34, P < 0.001), and the prediction was significantly enhanced by further inclusion of the Brief Pain Inventory interference score (total r = 0.40, P < 0.001). Conclusions: The study demonstrated that a significant correlation exists between the PSQ-E and clinically relevant pain ratings. This study validates the PSQ-E both in terms of measuring pain sensitivity and as possible means of recognizing patients with high pain sensitivity. Defining this subset of patients may have clinical utility in the future

Hypercomplex polynomials, vietoris’ rational numbers and a related integer numbers sequence

This paper aims to give new insights into homogeneous hypercomplex Appell polynomials through the study of some interesting arithmetical properties of their coefficients. Here Appell polynomials are introduced as constituting a hypercomplex generalized geometric series whose fundamental role sometimes seems to have been neglected. Surprisingly, in the simplest non-commutative case their rational coefficient sequence reduces to a coefficient sequence S used in a celebrated theorem on positive trigonometric sums by Vietoris (Sitzungsber Österr Akad Wiss 167:125–135, 1958). For S a generating function is obtained which allows to derive an interesting relation to a result deduced by Askey and Steinig (Trans AMS 187(1):295–307, 1974) about some trigonometric series. The further study of S is concerned with a sequence of integers leading to its irreducible representation and its relation to central binomial coefficients.The work of the first and third authors was supported by Portuguese funds through the CIDMA - Center for Research and Development in Mathematics and Applications, and the Portuguese Foundation for Science and Technology (“FCT-Fundação para a Ciência e Tecnologia”), within project PEstOE/MAT/UI4106/2013. The work of the second author was supported by Portuguese funds through the CMAT - Centre of Mathematics and FCT within the Project UID/MAT/00013/2013.info:eu-repo/semantics/publishedVersio

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Excellent Response to OnabotulinumtoxinA: Different Definitions, Different Predictors

The identification of patients who can benefit the most from the available preventive treatments is important in chronic migraine. We explored the rate of excellent responders to onabotulinumtoxinA in a multicenter European study and explored the predictors of such response, according to different definitions. A pooled analysis on chronic migraineurs treated with onabotulinumtoxinA and followed-up for, at least, 9 months was performed. Excellent responders were defined either as patients with a ≥75% decrease in monthly headache days (percent-based excellent responders) or as patients with &lt;4 monthly headache days (frequency-based excellent responders). The characteristics of excellent responders at the baseline were compared with the ones of patients with a &lt;30% decrease in monthly headache days. Percent-based excellent responders represented about 10% of the sample, whilst frequency-based excellent responders were about 5% of the sample. Compared with non-responders, percent-based excellent responders had a higher prevalence of medication overuse and a higher excellent response rate even after the 1st and the 2nd injection. Females were less like to be frequency-based excellent responders. Chronic migraine sufferers without medication overuse and of female sex may find fewer benefits with onabotulinumtoxinA. Additionally, the excellent response status is identifiable after the first cycle

Epicrania fugax with backward radiation: clinical characteristics of nine new cases

Epicrania fugax (EF) is a novel syndrome, described as a paroxysmal and brief head pain, starting in posterior cranial regions and rapidly spreading forward ipsilateral eye, nose or forehead. Two patients with comparable clinical features stemming from frontal scalp to ipsilateral posterior regions have been recently described and proposed as backward radiation epicrania fugax (BREF). We report a new series of nine BREF and compare their clinical characteristics with 18 forward radiation EF (FREF). Since first description of BREF in February 2010 we have assessed nine patients (four males, five females) with this clinical picture at an outpatient headache office in a Tertiary Hospital. Comparison is established with 18 FREF patients (6 males, 12 females), attended since the publication of first series of EF in March 2008. We found no differences between BREF and FREF, respectively, in age at onset (43.4 ± 13.1 vs. 42.5 ± 17.7 years), female/male ratio (5/4 vs. 12/6), pain intensity (6.9 ± 2.1 vs. 6.8 ± 2.1 in a 0–10 visual analogical scale), duration (7.1 ± 4.9 vs. 5.7 ± 4.3 s) and frequency of episodes per day (7 ± 8.4 vs. 9.9 ± 15.4). Patients in BREF group presented less frequently interictal pain in stemming point (22.2 vs. 55.5%) and accompanying autonomic signs (33.3 vs. 55.5%), but without statistical significance in both the cases. This series reinforces the proposal of EF as a new headache variant or a new headache syndrome. Clinical picture of brief pain paroxysms starting in the anterior scalp and radiating backwards does not fit known headaches or neuralgias and might correspond to a reverse variant of EF, clinical characteristics of which are comparable to FREF

Mast Cell-Derived Histamine Mediates Cystitis Pain

Background: Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC) is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC. Methods and Findings: Infection of mice with pseudorabies virus (PRV) induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF), TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology. Conclusions: These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, an