Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.

Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, non-pharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain

Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge.

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output

Xenomelia: a new right parietal lobe syndrome

ABSTRACT Background Damage to the right parietal lobe has long been associated with various disorders of body image. The authors have recently suggested that an unusual behavioural condition in which otherwise rational individuals desire the amputation of a healthy limb might also arise from right parietal dysfunction. Methods Four subjects who desired the amputation of healthy legs (two right, one left and one, at first, bilateral and then left only) were recruited and underwent magnetoencephalography (MEG) scans during tactile stimulation of sites above and below the desired amputation line. Regions of interest (ROIs) in each hemisphere (superior parietal lobule (SPL), inferior parietal lobule, S1, M1, insula, premotor cortex and precuneus) were defined using FreeSurfer software

Frontal and superior temporal auditory processing abnormalities in schizophrenia

AbstractBackgroundAlthough magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex.MethodsThe standard paired-click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial–temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130ms. Within-group t-tests compared post-stimulus 50ms and 100ms activity to baseline. Between-group t-tests examined 50 and 100ms group differences.ResultsBilateral 50 and 100ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC.ConclusionsLess STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network

Modification of Chitosan-Pectin Beads Adsorbent and Its Application for the Removal of Pb (II) from C-phycocyanin

Chitosan-pectin gel beads (CPB) have high potential for removing heavy metals from food. This study aimed to improve their stability, recyclability, and adsorption capacity by modified CPB with gelatin (Gel) and carboxymethyl cellulose sodium (CMC). The structural characteristics of the modified CPBs were characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), Zeta potential, scanning electron microscopy (SEM), pore size distribution analysis (BET), X-ray photoelectron spectroscopy (XPS), specific surface area analysis. The adsorption-resolution conditions of modified CPB were optimized, and their actual removal efficiency for Pb(II) in C-phycocyanin was evaluated. Results showed that CMC-modified CPB (CMC-CPB) had higher thermal stability, rougher and more porous surface, larger specific surface area (20.28±1.35 m2/g), lower zeta potential, stronger metal ion adsorption capacity, and higher regeneration efficiency compared with CPB and Gel-CPB. FTIR showed the functional group of CPB had significant difference after modification, and the main group in CPB were carboxyl, hydroxyl, and amino groups. TG analysis presented the thermal stability of CMC-CPB was higher than that of CPB and Gel-CPB. XPS analysis showed CMC-CPB had the strongest absorption peak for Pb(II). The optimal pH and temperature for the three adsorbents (CPB, Gel-CPB, and CMC-CPB) to remove Pb(II) were 6.0 and 60 ℃, respectively. The Pb(II) adsorption process of all three adsorbents fit the Langmuir isotherm model (R2=0.9543~0.9811) and the pseudo-second-order kinetic model (R2=0.9963~0.9991), and the adsorption process belonged to the monolayer chemical adsorption, involving the complexation of -COO, -OH, -CO-NH, and Pb(II). Based on the Langmuir model curve, the maximum adsorption capacity (qmax) of CMC-CPB for Pb(II) was 69.37 mg/g, significantly higher than that of Gel-CPB and CPB (P<0.05). Combing application effect of three adsorbents in C-phycocyanin, CMC-CPB showed a great prospect to efficiently remove Pb(II) in food of algae and C-phycocyanin at low-cost and environment friendly

Congenital insensitivity to pain associated with PRDM12 mutation: Two case reports and a literature review

Background:PRDM12 is a newly discovered gene responsible for congenital insensitivity to pain (CIP). Its clinical manifestations are various and not widely known.Methods: The clinical data of two infants diagnosed with CIP associated with PRDM12 mutation were collected. A literature review was performed, and the clinical characteristics of 20 cases diagnosed with a mutation of PRDM12 were summarized and analyzed.Results: Two patients had pain insensitivity, tongue and lip defects, and corneal ulcers. The genomic analysis results showed that variants of PRDM12 were detected in the two families. The case 1 patient carried heterozygous variations of c.682+1G &gt; A and c.502C &gt; T (p.R168C), which were inherited from her father and mother, respectively. We enrolled 22 patients diagnosed with CIP through a literature review together with our cases. There were 16 male (72.7%) and 6 female (27.3%) patients. The age of onset ranged from 6 months to 57 years. The prevalence of clinic manifestation was 14 cases with insensitivity to pain (63.6%), 19 cases with self-mutilation behaviors (86.4%), 11 cases with tongue and lip defects (50%), 5 cases with mid-facial lesions (22.7%), 6 cases with distal phalanx injury (27.3%), 11 cases of recurrent infection (50%), 3 cases (13.6%) with anhidrosis, and 5 cases (22.7%) with global developmental delay. The prevalence of ocular symptoms was 11 cases (50%) with reduced tear secretion, 6 cases (27.3%) with decreased corneal sensitivity, 7 cases (31.8%) with disappeared corneal reflexes, 5.5 cases (25%, 0.5 indicated a single eye) with corneal opacity, 5 cases (22.7%) with corneal ulceration, and 1 case (4.5%) with a corneal scar.Conclusion: The syndrome caused by PRDM12 mutation is a clinically distinct and diagnosable disease that requires joint multidisciplinary management to control the development of the disease and minimize the occurrence of complications

Divergent Cortical Generators of MEG and EEG during Human Sleep Spindles Suggested by Distributed Source Modeling

Background: Sleep spindles are,1-second bursts of 10–15 Hz activity, occurring during normal stage 2 sleep. In animals, sleep spindles can be synchronous across multiple cortical and thalamic locations, suggesting a distributed stable phaselocked generating system. The high synchrony of spindles across scalp EEG sites suggests that this may also be true in humans. However, prior MEG studies suggest multiple and varying generators. Methodology/Principal Findings: We recorded 306 channels of MEG simultaneously with 60 channels of EEG during naturally occurring spindles of stage 2 sleep in 7 healthy subjects. High-resolution structural MRI was obtained in each subject, to define the shells for a boundary element forward solution and to reconstruct the cortex providing the solution space for a noise-normalized minimum norm source estimation procedure. Integrated across the entire duration of all spindles, sources estimated from EEG and MEG are similar, diffuse and widespread, including all lobes from both hemispheres. However, the locations, phase and amplitude of sources simultaneously estimated from MEG versus EEG are highly distinct during the same spindles. Specifically, the sources estimated from EEG are highly synchronous across the cortex, whereas those from MEG rapidly shift in phase, hemisphere, and the location within the hemisphere. Conclusions/Significance: The heterogeneity of MEG sources implies that multiple generators are active during huma