Maternal separation in mice leads to anxiety-like/aggressive behavior and increases immunoreactivity for glutamic acid decarboxylase and parvalbumin in the adolescence ventral hippocampus.

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

mGlu1 receptor mediates homeostatic control of intrinsic excitability through Ih in cerebellar Purkinje cells.

Homeostatic intrinsic plasticity is a cellular mechanism for maintaining a stable neuronal activity level in response to developmental or activity-dependent changes. Type 1 metabotropic glutamate receptor (mGlu1 receptor) has been widely known to monitor neuronal activity, which plays a role as a modulator of intrinsic and synaptic plasticity of neurons. Whether mGlu1 receptor contributes to the compensatory adjustment of Purkinje cells (PCs), the sole output of the cerebellar cortex, in response to chronic changes in excitability remains unclear. Here, we demonstrate that the mGlu1 receptor is involved in homeostatic intrinsic plasticity through the upregulation of the hyperpolarization-activated current (Ih) in cerebellar PCs. This plasticity was prevented by inhibiting the mGlu1 receptor with Bay 36-7620, an mGlu1 receptor inverse agonist, but not with CPCCOEt, a neutral antagonist. Chronic inactivation with tetrodotoxin (TTX) increased the components of Ih in the PCs, and ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated channel selective inhibitor, fully restored reduction of firing rates in the deprived neurons. The homeostatic elevation of Ih was also prevented by BAY 36-7620, but not CPCCOEt. Furthermore, KT 5720, a blocker of protein kinase A (PKA), prevented the effect of TTX reducing the evoked firing rates, indicating the reduction in excitability of PCs due to PKA activation. Our study shows that both the mGlu1 receptor and the PKA pathway are involved in the homeostatic intrinsic plasticity of PCs after chronic blockade of the network activity, which provides a novel understanding on how cerebellar PCs can preserve the homeostatic state under activity-deprived conditions.

The High Performance of Crystal Water Containing Manganese Birnessite Cathodes for Magnesium Batteries.

Rechargeable magnesium batteries have lately received great attention for large-scale energy storage systems due to their high volumetric capacities, low materials cost, and safe characteristic. However, the bivalency of Mg(2+) ions has made it challenging to find cathode materials operating at high voltages with decent (de)intercalation kinetics. In an effort to overcome this challenge, we adopt an unconventional approach of engaging crystal water in the layered structure of Birnessite MnO2 because the crystal water can effectively screen electrostatic interactions between Mg(2+) ions and the host anions. The crucial role of the crystal water was revealed by directly visualizing its presence and dynamic rearrangement using scanning transmission electron microscopy (STEM). Moreover, the importance of lowering desolvation energy penalty at the cathode-electrolyte interface was elucidated by working with water containing nonaqueous electrolytes. In aqueous electrolytes, the decreased interfacial energy penalty by hydration of Mg(2+) allows Birnessite MnO2 to achieve a large reversible capacity (231.1 mAh g(-1)) at high operating voltage (2.8 V vs Mg/Mg(2+)) with excellent cycle life (62.5% retention after 10000 cycles), unveiling the importance of effective charge shielding in the host and facile Mg(2+) ions transfer through the cathode's interface.

Examination of medical students' opinions on multimedia learning materials according to social cues: focusing on sound principles.

PURPOSE: Although interest in various forms of learning media is increasing due to the coronavirus disease 2019 (COVID-19) pandemic there is relatively little research on influencing student motivation by intervening in cognitive processing. The purpose of this study was to present the optimal form of learning materials provided to medical students. METHODS: This study provided learning materials in class at a level according to social cues (script, video [artificial intelligence (AI) voice], video [professor voice]) based on the principle of voices among the principles of personalization, voices, image, and embodiment of social cues in multimedia learning, and surveyed students' opinions. RESULTS: There was no statistically significant difference according to social clues in satisfaction and learning help, but both appeared in the order of silent videos containing the professor's voice, followed by videos containing the AI voice. CONCLUSION: This study is significant in that there is no research on the impact of student motivation on the provision of learning materials for medical school education in Korea, and we hope that it will help provide learning materials for self-directed learning of medical students in the post-COVID-19.

Enhancing Microalgae Content in Biocomposites through a Mechanical Grinding Method.

Microalgae-based biocomposites are gaining traction as ecofriendly and cost-effective alternatives to conventional petroleum-based plastics. However, achieving a homogeneous dispersion of microalgae within a biocomposite matrix remains a challenge. In this study, we investigated the effect of the size of dried microalgae (Chlorella sp.) on the quality of biocomposites. Ball milling, a mechanical grinding process, was used to control the size of the pretreated dried microalgae. Our results demonstrate that the microalgae size strongly depends on the total weight of the stainless-steel balls, rather than the number of balls used in the milling process. Poly(ethylene-vinyl acetate) (EVA), with functional groups resembling those of Chlorella sp., was incorporated into the ball-milled microalgae to produce homogeneous biocomposites. Smaller Chlorella sp. particles improved the ratio of microalgae and the mechanical properties of the biocomposites. Dried Chlorella sp. particles up to 161.43 µm, which were 72.84% smaller than the untreated microalgae, were obtained after 6 h of ball milling using 3/8-inch balls. This enabled the production of biocomposites with 60 wt.% microalgae and 61.02% of the tensile strength of pure EVA, comparable to traditional polymers. Our findings suggest that controlling the microalgae size through ball milling can improve the quality of microalgae-based biocomposites.

Trans-Anethole Alleviates Trimethyltin Chloride-Induced Impairments in Long-Term Potentiation.

Trans-anethole is an aromatic compound that has been studied for its anti-inflammation, anticonvulsant, antinociceptive, and anticancer effects. A recent report found that trans-anethole exerted neuroprotective effects on the brain via multiple pathways. Since noxious stimuli may both induce neuronal cell injury and affect synaptic functions (e.g., synaptic transmission or plasticity), it is important to understand whether the neuroprotective effect of trans-anethole extends to synaptic plasticity. Here, the effects of trimethyltin (TMT), which is a neurotoxic organotin compound, was investigated using the field recording method on hippocampal slice of mice. The influence of trans-anethole on long-term potentiation (LTP) was also studied for both NMDA receptor-dependent and NMDA receptor-independent cases. The action of trans-anethole on TMT-induced LTP impairment was examined, too. These results revealed that trans-anethole enhances NMDA receptor-dependent and -independent LTP and alleviates TMT-induced LTP impairment. These results suggest that trans-anethole modulates hippocampal LTP induction, prompting us to speculate that it may be helpful for improving cognitive impairment arising from neurodegenerative diseases, including Alzheimer's disease.

Enhanced proton treatment with a LDLR-ligand peptide-conjugated gold nanoparticles targeting the tumor microenvironment in an infiltrative brain tumor model.

The tumor microenvironment (TME) of glioblastoma malforms (GBMs) contains tumor invasiveness factors, microvascular proliferation, migratory cancer stem cells and infiltrative tumor cells, which leads to tumor recurrence in the absence of effective drug delivery in a Blood Brain Barrier (BBB)-intact TME and radiological invisibility. Low-density lipoprotein receptor (LDLR) is abundant in the blood brain barrier and overexpressed in malignant glioma cells. This study aimed to treat the TME with transmitted proton sensitization of LDLR ligand-functionalized gold nanoparticles (ApoB@AuNPs) in an infiltrative F98 glioma rat model. BBB-crossing ApoB@AuNPs were selectively taken up in microvascular endothelial cells proliferation and pericyte invasion, which are therapeutic targets in the glioma TME. Proton sensitization treated the TME and bulk tumor volume with enhanced therapeutic efficacy by 67-75% compared to that with protons alone. Immunohistochemistry demonstrated efficient treatment of endothelial cell proliferation and migratory tumor cells of invasive microvessels in the TME with saving normal tissues. Taken together, these data indicate that the use of LDLR ligand-functionalized gold nanoparticles is a promising strategy to treat infiltrative malignant glioma while overcoming BBB crossing.

A high-precision micropipette sensor for cellular-level real-time thermal characterization.

We report herein development of a novel glass micropipette thermal sensor fabricated in a cost-effective manner, which is capable of measuring steady thermal fluctuation at spatial resolution of ∼2 µm with an accuracy of ±0.01 °C. We produced and tested various micrometer-sized sensors, ranging from 2 µm to 30 µm. The sensor comprises unleaded low-melting-point solder alloy (Sn-based) as a core metal inside a pulled borosilicate glass pipette and a thin film of nickel coating outside, creating a thermocouple junction at the tip. The sensor was calibrated using a thermally insulated calibration chamber, the temperature of which can be controlled with an accuracy of ±0.01 °C, and the thermoelectric power (Seebeck coefficient) of the sensor was recorded from 8.46 to 8.86 µV/°C. We have demonstrated the capability of measuring temperatures at a cellular level by inserting our temperature sensor into the membrane of a live retinal pigment epithelium cell subjected to a laser beam with a focal spot of 6 µm. We measured transient temperature profiles and the maximum temperatures were in the range of 38-55 ± 0.5 °C.

Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-ß Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer's Disease Mouse Model.

BACKGROUND: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer's disease (AD), and the formation of amyloid-ß (Aß) plaques induces critical impairment of cognitive function. OBJECTIVE: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. METHODS: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aß plaques by electron emission from magnetite. The reduction in Aß plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aß-magnetite and Aß fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. RESULTS: Single PS induced a 48-87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aß plaque burden (68-82%) and (94-97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p < 0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aß fibrils. CONCLUSION: Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.

Delta- and mu-opioid pathways are involved in the analgesic effect of Ocimum basilicum L in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum basilicum L. is a perennial herb that has been used in traditional Asian Indian medicine for thousands of years as a natural anti-inflammatory, antibiotic, diuretic, and analgesic. AIM OF THE STUDY: The present study was conducted to investigate the analgesic effects of basil essential oil (BEO) in inflammatory pain models and identify underlying mechanisms. We further investigated whether BEO affects physiological pain and motor coordination. MATERIALS AND METHODS: The analgesic effects of BEO were assessed in various mouse experimental pain models using formalin, acetic acid, heat, and carrageenan as stimuli. BEO was administered by intraperitoneal injection or inhalation. The involvement of various pathways in the analgesic effect of BEO was assessed by pretreating mice with selective pharmacological inhibitors, administered intraperitoneally. Opioid pathways were tested using the κ-opioid antagonist 5'-guanidinonaltrindole (GNTI; 0.3 mg/kg), δ-opioid antagonist naltrindole (NTD; 5 mg/kg) and µ-opioid antagonist naloxone (NAL; 8 mg/kg); nitric oxide (NO) pathways were tested using the NO synthase inhibitor N-nitro l-arginine methyl ester (L-NAME; 37.5 mg/kg) and NO precursor L-arginine (L-Arg; 600 mg/kg); and KATP channel pathways were tested using the ATP-sensitive K+ channel blocker, glibenclamide-hippuric acid (GHA, 2 mg/kg). Potential effects of BEO on motor coordination were assessed using a rotarod test. RESULTS: BEO exerted analgesic effects in all pain models. Notably, pretreatment with naltrindole, naloxone, or L-arginine significantly reduced the analgesic effects of BEO in the formalin test. BEO increased mean withdrawal latencies in a thermal plantar test at a high dose, but not at lower doses. BEO had no effect on motor coordination. CONCLUSIONS: Our findings indicate that the analgesic effects of BEO are primarily mediated by delta- and mu-opioid pathways and further suggest that BEO has potential for development as an analgesic agent for the relief of inflammatory pain.

Neuregulin-1 inhibits CoCl2-induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice.

Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl2 is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl2 induced significant EAAC1 overexpression in SH-SY5Y cells and the hippocampus of mice. Transient transfection of EAAC1 reduced CoCl2-induced cytotoxicity in SH-SY5Y cells. Based on this result, upregulation of EAAC1 expression by CoCl2 is thought to represent a compensatory response against oxidative stress in an acute hypoxic state. We further demonstrated that pretreatment with Neuregulin-1 (NRG1) rescued CoCl2-induced upregulation of EAAC1 and tau expression. NRG1 plays a protective role in the CoCl2-induced accumulation of reactive oxygen species (ROS) and reduction in antioxidative enzyme (SOD and GPx) activity. Moreover, NRG1 attenuated CoCl2-induced apoptosis and cell death. NRG1 inhibited the CoCl2-induced release of cleaved caspase-3 and reduction in Bcl-XL levels. Our novel finding suggests that NRG1 may play a protective role in hypoxia through the inhibition of oxidative stress and thereby maintain normal EAAC1 expression levels.

Haemodynamic changes and incisional bleeding after scalp infiltration of dexmedetomidine with lidocaine in neurosurgical patients.

BACKGROUND: The purpose of this randomised controlled study is to compare the haemodynamic changes and the degree of incisional bleeding after scalp infiltration of lidocaine and dexmedetomidine versus lidocaine and epinephrine for patients with hemi-facial spasm undergoing microvascular decompression. METHODS: Fifty-two patients were injected with 5 mL of 1% lidocaine with either dexmedetomidine (2 µg/mL) or epinephrine (1:100,000 dilution) to reduce scalp bleeding. Mean blood pressure and heart rate were recorded every minute for 15 minutes after scalp infiltration. The primary outcome was the incidence of predefined hypotension, which was treated with administration of 4 mg ephedrine as often as needed. The number of administrations and total amount of ephedrine administered were also recorded as a measure of the severity of hypotension. The neurosurgeon scored incisional bleeding by numeric rating scale from 0 (worst) to 10 (best). RESULTS: The incidence of hypotension (68% vs. 34.8%, P = 0.02) and the frequency (P = 0.02) and total dose (P = 0.03) of ephedrine administered were lower in the dexmedetomidine group than in the epinephrine group. In addition, there was no difference in mean blood pressure between the two groups but heart rates were lower in the dexmedetomidine group (P = 0.01). Incisional site bleeding was better with epinephrine (median [interquartile range] of the numeric rating Score: 6 [4] in the dexmedetomidine group and 8 [2] in the epinephrine group; P < 0.001). CONCLUSION: The dexmedetomidine-lidocaine combination may be recommended as a substitute for epinephrine-lidocaine for scalp infiltration in neurosurgical patients, especially neurologically compromised patients.

Author Correction: PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.

In the version of this article initially published, what was originally described as 'conditioned place preference' in a two-chamber mouse experiment could be better described as 'conditioned place avoidance'.

Thermo-sensitive nanogel-laden bicontinuous microemulsion drug-eluting contact lenses.

The bicontinuous microemulsion contact lens (BMCL) has nanoporous biphasic structures (100-250 nm) that are interconnected via multiple nano-channels, providing suitable retention of various drugs for glaucoma. Timolol maleate (TM)-carried thermosensitive poly(N-isopropylacrylamide) (PNIPAM) nanogel (30-50 nm) was incorporated into BMCLs by soaking or by centrifuging plus soaking. Here, we present drug-loading and release in silicon- or polyethylene oxide-microemulsion BMCLs under various conditions. Nanoporous BMCLs containing thermosensitive TM-laden nanogel were capable of potent body-temperature-triggered release of TM. Daily drug release was controllable according to the initial volume of drug-loaded (VDL) and loading method for sustained drug release, making them reduce drug-loss during transportation or storage. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1159-1169, 2019.

Resolution enhancing using cantilevered tip-on-aperture silicon probe in scanning near-field optical microscopy.

Scanning near-field optical microscopy (SNOM) achieves a resolution beyond the diffraction limit of conventional optical microscopy systems by utilizing subwavelength aperture probe scanning. A problem associated with SNOM is that the light throughput decreases markedly as the aperture diameter decreases. Apertureless scanning near-field optical microscopes obtain a much better resolution by concentrating the light field near the tip apex. However, a far-field illumination by a focused laser beam generates a large background scattering signal. Both disadvantages are overcome using the tip-on-aperture (TOA) approach, as presented in previous works. In this study, a finite difference time domain analysis of the degree of electromagnetic field enhancement is performed to verify the efficiency of TOA probes. For plasmon enhancement, silver is deposited on commercially available cantilevered SNOM tips with 20 nm thicknesses. To form the aperture and TOA in the probes, electron beam-induced deposition and focused ion beam machining were applied at the end of the sharpened tip. The results show that cantilevered TOA probes were highly efficient for improvements of the resolution of optical and topological measurement of nanostructures.

Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel.

Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1.7 (~18%). To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel (0.1-1 µmol/L) for 24 h. Paclitaxel increased the Nav1.7 but not Nav1.8 expression and also increased the transient Na+ currents and action potential firing frequency in small-diameter (<50 µm) hDRG neurons. Thus, the hDRG provides a translational model in which to study "human pain in a dish" and test new pain therapeutics.

Piperidinium ionic liquids as electrolyte solvents for sustained high temperature supercapacitor operation.

The synthesis and physicochemical properties of a series of non-flammable, thermally stable alkyl ether containing piperidinium ionic liquid electrolytes, containing lithium bis(trifluoromethanesulfonyl)imide, are described along with the superior performance of a lithium-ion supercapacitor containing a piperidinium electrolyte compared to a standard carbonate-based electrolyte at 100 °C.

Long-distance transmission of broadband near-infrared light guided by a semi-disordered 2D array of metal nanoparticles.

Near-infrared (NIR) waveguides are a key component of planar photonic devices such as optical communication couplers, image sensors, and spectroscopes for chemical or biological molecules. Conventional NIR waveguides used for signal transmission include silicon-on-insulator (SOI) waveguides and channel/ridge-type metal micro-strips. However, these waveguides usually have limitations of either signal delay or signal loss in optically integrated devices. In this study, a novel NIR waveguide composed of a semi-disordered array of metal nanoparticles (sDAMNPs) on Si substrate was proposed, fabricated, and tested. The disordered metallic nanoparticles array is geometrically localized in the form of 1D metal strips, thus replacing sDAMNPs with less lossy micro strip channel waveguides. From the measurements supported by various computational models, the fabricated waveguides operate effectively in the broadband NIR region (1100 to 1700 nm). The waveguide does not support signal transmission in the ultra violet-visible spectrum due to strong signal absorption, scattering, and localization effects inside the metal nanoparticles. Instead, it is capable of transmitting NIR over a distance longer than 100 µm (signal loss ∼3.85 dB per 100 µm for NIR from 1200 to 1600 nm), which is also sufficiently longer than the conventional surface plasmon polariton propagation distance at the metal-Si interface. Compared to a waveguide-free reference, the waveguide exhibited greatly improved signal transmission efficiency up to a factor of 7.42 × 104 at 1367 nm. It also exhibits a high deflection angle sensitivity of 1.89 dB per 0.01 rad, thus efficiently and straightly guiding the broadband NIR signal over a long distance.

Postoperative Gamma Knife Radiosurgery for Cavernous Sinus-Invading Growth Hormone-Secreting Pituitary Adenomas.

OBJECTIVE: We aimed to determine the long-term effects of Gamma knife radiosurgery (GKS) on remnants in the cavernous sinus (CS) after transsphenoidal surgery (TSS) for acromegaly and to identify its possible adverse effects. METHODS: Thirty patients who had remnant tumors only inside the CS after TSS and who consequently underwent GKS were included. They were followed for a median period of 47 months after GKS with regular hormonal and radiologic examinations. RESULTS: The mean tumor volume and margin dose irradiated by GKS was 3.7 cm3 and 26.2 Gy, respectively. Radiologic tumor control was identified in all patients, and no tumor regrowth or recurrent tumors were identified. For 14 patients who achieved endocrinologic remission, the median duration from GKS until remission was 35 months. The actuarial rates of remission at 2, 5, and 10 years were 7.1%, 43.6%, and 65.6%, respectively. The degree of decrease in the nadir GH level in the OGTT at 6 months after GKS was a statistically significant predictor of remission. Newly developed hypopituitarism frequently developed in a time-dependent manner. Radiation necrosis developed in 4 patients with relatively large remnant volumes. CONCLUSIONS: GKS is an effective adjuvant treatment option for remnant tumors inside the CS after TSS. Maximal surgical resection, leaving minimal volume of remnants only inside the CS, allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS.

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies.

The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na+ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.