Reduction In Threshold Research Articles

Blue micro-lasing from dye-doped hollow polymer optical fiber with an Ag nanoparticle-doped microring

We report the modified and improved whispering gallery mode laser emission from a hollow polymer optical fiber doped with 1,4-Bis(2-methyl styryl) benzene (Bis-MSB), a high-quantum yield dye with a blue emission, with the introduction of an Ag nanoparticle-doped microring. In the presence of the Ag-doped microring, the laser emission was enhanced, and a reduction in the laser threshold from 40 to 15 µJ was attained, along with a small redshift in the emission spectrum. The quality factor of the microring embedded hollow polymer optical fiber was found to be 1.3×103. Moreover, the introduction of an Ag-doped microring inside the hollow polymer optical fiber helps enhance certain lasing modes. The observations open the way for the development of low-threshold polymer optical fiber lasers in the blue region.

Endoscopic Findings on Facial Nerve Anatomy During Exclusive Endoscopic Stapedotomy: Clinical Considerations and Impact on Surgical Results.

Variations along the facial nerve (FN) course present considerable challenges in the surgical treatment of otosclerosis, often complicating the procedure. Existing knowledge of its tympanic tract and its implications primarily comes from microscopical procedures. This study aims to assess endoscopic findings of FN anatomy in a healthy tympanic cavity and its impact on the stapedotomy procedure, focusing on the risk of complications and functional hearing outcomes. A retrospective study on exclusive endoscopic stapedotoplasties between October 2014 and October 2021 at our Otorhinolaryngology University Department was carried out. An evaluation of intraoperative endoscopic findings reviewed in surgical descriptive and/or video records was conducted to assess their potential negative impact on the surgery. Demographic data, preoperative and postoperative hearing thresholds, as well as intraoperative and postoperative complications were analyzed. One hundred fifty-seven subjects were included. A FN partially overhanging the oval window was observed in 7.3% (n=12): 10 prolapsing with bony canal dehiscence and 2 without any detected dehiscence. Each procedure was successfully completed without any issues related to the anomalous anatomy, and in no case, switching to the microscope for the handling of the prosthesis near the dehiscent nerve was required. No facial paralysis occurred, with an early- or long-term postoperative House-Brackman grade of 1 (n=157, 100%). Only 3/157 patients (1.9%) showed a sensorineural threshold reduction of ≥20 dB HL, but a significant air-bone gap improvement was observed (mean closure of 18.36 dB HL, P -lt; .0001). The endoscope promotes a concrete description of tympanic FN anatomy, and endoscopic stapes surgery appears to be a safe and viable option when dehiscent or prolapsed FNs reduce the footplate's exposure.

Dopamine antinociceptive system

The article presents modern views on structure and functioning of dopaminergic structures of the brain and spinal cord and their role in mechanisms of antinociception, formation, and chronification of different pain syndrome types. The paper provides a detailed description of analgesic effects of various dopamine receptors in the structures of the CNS (the spinal cord, ventral tegmental area, periaqueductal gray, corpus striatum, nucleus accumbens, hypothalamus, and medial prefrontal cortex) which function as the dopaminergic antinociceptive system. The results of numerous investigations carried out on models of neuropathic pain syndrome have shown that D2 dopamine receptors possess the greatest analgesic activity. Their antinociceptive mechanism of action is effectuated at the level of substantia gelatinosa of the spinal cord and cerebral dopaminergic structures. D1‑like receptors have lower analgesic activity and different mechanisms of action depending on localization within the brain. High availability of D2/D3 receptors in corpus striatum is indicative of a low synaptic level of endogenous dopamine and leads to reduction of pain perception threshold. On the contrary, low availability of D2/D3 receptors results in the increase of pain perception threshold. The dopaminergic antinociceptive system is characterized by a modulating effect on other neurotransmitter systems participating in nociception and antinociception. An important mechanism of antinociception of dopaminergic structures is connected with superadditivity and synergism of D2 receptors with opioid receptors. Proven participation of dopaminergic structures in pain perception and analgesia demonstrates a potential possible application of D2‑receptors agonists as an adjuvant method for achieving a greater effect in therapeutic multimodal schemes of analgesia.

Laser auriculotherapy associated with cupping therapy in chronic spinal pain: Randomized controlled clinical trial

BackgroundMusculoskeletal spine disorders are common causes of chronic pain and impair functionality. Laser auriculotherapy and cupping has played a significant role in the treatment of chronic pain. Objective: to evaluate the effect of laser auriculotherapy associated with cupping at systemic acupuncture points on chronic spinal pain. Methods: Randomized controlled clinical trial. Volunteers underwent three evaluations: an initial evaluation, a final evaluation immediately after the last intervention session, and a 15-day follow-up. The pain was identified using the numeric pain scale. The pain threshold was also evaluated against mechanical stimulation using a Digital Dynamometer at specific points in the cervical, thoracic and lumbar regions. Fifty individuals with chronic spinal pain, randomized into groups: experimental (n = 25), submitted to 10 sessions of auriculotherapy with laser and cupping therapy and control (n = 25). Results: The experimental group achieved pain intensity reduction between pre and post and follow-up moments (p < 0.0001), of greatest pain in the last seven days among all moments (p < 0.0001), of least pain in the pre with post moment (p = 0.006) and follow-up (p = 0.002), and an increased pain threshold between pre and post (p = 0.023). The control group achieved a reduction in the nociceptive threshold between pre and post (p = 0.001) and follow-up (p < 0.0001). The experimental group showed reduced pain intensity (p = 0.027) and greater pain (p = 0.005) after intervention and in pain intensity (p = 0.018), greater (p < 0.0001) and less pain (p = 0.025) at follow-up, compared to the control group. Conclusion: Auriculotherapy with laser associated with cupping therapy may effectively reduce pain intensity and increase the nociceptive threshold.

Threshold Reducing via Micro Rhombic Lasing Misalignment Step‐Cavity with a Simple and Universal Use

AbstractNanolasers with low‐threshold operation have been attracting attention for a long time. However, research on methods to lower thresholds has been stagnant and underreported. To provide a generalizable method for reducing thresholds, a stepped array cavity designed in this study is demonstrated to reduce the nanolaser excitation threshold. In the experiment, the rhomboid array cavity is fabricated by 3D printing and covered with Cu film. The mechanism of two cavity (cavity α and β) and five modes is designed and displayed for systematically illustrating the parameters of the different cavities and principles of the different oscillation modes. The lasing behavior of modes 1, 2, 4, and 5 is proved by the photoluminescence spectrum at room temperature with the threshold of 1.53 kW cm−2, 2.73 kW cm−2, 66.2 W cm−2, and 371 W cm−2. The optimum angle of incidence for obtaining lower thresholds in the range 40°–60° is suggested. The laser generation mechanism and polarization characteristics are provided. Finally, the method developed in this study uses a wide range of materials and gain modes to achieve a universal threshold reduction method. The results indicate that the designed method is effective and scalable for a wide range of typical materials and gain modes.

Non-noble plasmonic nanowires enhanced flexible random lasers

We conducted an investigation on a flexible random laser (RL) device featuring non-noble plasmonic enhancement and scattering. The RL device was created by integrating copper nanowires (Cu NWs) and laser dyes (rhodamine 6G, R6G) into an acrylamide (AM) hydrogel matrix. The substantial overlap between the plasmonic resonance of Cu NWs and the emission of R6G effectively mitigates the requirements for lasing generation. Furthermore, the robust scattering induced by the three-dimensional distribution of Cu NWs contributes to a reduction in the laser threshold. Notably, the unique properties of the AM hydrogel ensure that the laser device exhibits excellent tensile recovery performance. The RL device is capable of maintaining stable lasing performance even after 100 % tensile deformation. This flexible laser device offers the advantages of a straightforward fabrication process, low cost, and robust lasing characteristics, thus paving the way for their advanced application in the future.

The effect of plasma toroidal rotation on n = 1 resonant magnetic perturbation field penetration under low neutral beam injection torque in EAST

An experiment was conducted to study the mode penetration of n=1 resonant magnetic perturbation (RMP) in EAST under low neutral beam injection torque in the co-current direction (Co-NBI). The experimental results indicate that the threshold current IRMP,th for field penetration decreases with higher input torque TNBI . Furthermore, it is observed that the plasma mode frequency |fMHD| at counter-current direction is greatly reduced when the plasma toroidal rotation frequency fϕ increases. The theoretical scaling of mode frequency (IRMP,th∝|fMHD|0.70) predicted by the field penetration theory is in good agreement with the experimental observation ( IRMP,th∝|fMHD|0.53 ). The role of |fMHD| and fϕ on the mode onset threshold was separately investigated using the full toroidal geometry initial value code MARS-Q (Liu et al 2013 Phys. Plasmas 20 042503). The numerical scaling based on the experimental mode frequency is consistent with the experimental and theoretical ones. Numerical results suggest that evaluating the total mode frequency |fMHD| is crucial in field penetration analysis, in contrast to toroidal rotation frequency fϕ . With the increase of TNBI , the decreasing |fMHD| leads to a reduction in the field penetration threshold. This suggests that more attention should be paid to error field tolerance in low Co-NBI torque scenarios, where the electron diamagnetic frequency may be canceled out by NBI-driven toroidal plasma rotation.

Optical bistability modulation based on graphene sandwich structure with topological interface modes.

In this paper, we have investigated optical bistability modulation of transmitted beam that can be achieved by graphene sandwich structure with topological interface modes at terahertz frequency. Graphene with strong nonlinear optical effect was combined with sandwich photonic crystal to form a new sandwich structure with topological interface modes. The light-limiting properties of the topological interface modes, as well as its high unidirectionality and high transmission efficiency, all contribute positively to the reduction of the optical bistability threshold. In addition, the topological interface modes can effectively ensure the stability of the two steady state switching in the case of external interference. Moreover, optical bistability is closely related to the incident angle, the Fermi energy, the relaxation time, and the number of layers of graphene. Through parameter optimization, optical bistability with threshold of 105 V/m can be obtained, which has reached or is close to the range of the weak field.

Multipole engineering by displacement resonance: a new degree of freedom of Mie resonance

The canonical studies on Mie scattering unravel strong electric/magnetic optical responses in nanostructures, laying foundation for emerging meta-photonic applications. Conventionally, the morphology-sensitive resonances hinge on the normalized frequency, i.e. particle size over wavelength, but non-paraxial incidence symmetry is overlooked. Here, through confocal reflection microscopy with a tight focus scanning over silicon nanostructures, the scattering point spread functions unveil distinctive spatial patterns featuring that linear scattering efficiency is maximal when the focus is misaligned. The underlying physical mechanism is the excitation of higher-order multipolar modes, not accessible by plane wave irradiation, via displacement resonance, which showcases a significant reduction of nonlinear response threshold, sign flip in all-optical switching, and spatial resolution enhancement. Our result fundamentally extends the century-old light scattering theory, and suggests new dimensions to tailor Mie resonances.

Random lasing in dye-doped electrospun PMMA fibers with different emission modes

Random lasers (RLs) have significant applications in micro-nano light emitters, micro-detection, and speckle-free imaging due to their novel properties in low spatial coherence, small size and multi-emission directions. A flexible, affordable approach for creating new scattering materials has recently been suggested for electrospun fibers, which are practical materials for RLs. In this article, we employ the electrospun PMMA fibers as scatters and the DCJTB as gain materials to generate an RL system. The sample shows obvious incoherent random lasing properties. A decrease of the lasing threshold by 32 % is realized when we increase the electrospun voltage from 12 kV to 15 kV due to the generation of a small mean diameter size and concentrated diameter distribution. The lasing threshold of the DCJTB/Au NPs-doped PMMA sample is further reduced to 19.8 μJ/mm2 by incorporating Au NPs into the electrospun dye-doped fibers. This leads to a lasing threshold reduction of 40 % from the electrospun sample without doping Au NPs and 52 % from the spin-coated film sample, respectively. It indicates that the electrospun method is an efficient and practical approach to make RLs. Furthermore, using single pulse laser stimulation, we investigated several different lasing modes, including spontaneous emission, short wavelength domain, mode competition, and single mode. The actions of photon scattering are analyzed to explain the dramatic lasing process. Due to the photon scattering optical path, there are mode competition and single mode emission regions under different pump energy. The light spot quality of RL shows low spatial coherence with the useful application of speckle-free imaging. This research provides a new method of electrospun to produce low-threshold and high-quality RLs and potentially opens the door for expanding their use in optics and optoelectronic equipment.

High-power sub-picosecond filamentation at 1.03 µ m with high repetition rates between 10 and 100 kHz

Filamentation has extensively been explored and is well understood at repetition rates &amp;lt;1 kHz due to the typical availability of multi-mJ laser systems at a moderate average power. The advent of high-power Yb-lasers opened new possibilities for filamentation research. However, so far, high average power Yb systems have mostly been explored to increase the driving pulse energy to several hundreds of mJ and not at significantly higher repetition rates. In this paper, we study, for the first time, long filaments at unprecedented high repetition rates of 10, 40, and 100 kHz using a 500-W Yb-doped thin-disk amplifier driver operating with sub-700 fs pulses. We compare the filament length, density hole, and fluorescence at a constant peak power but different repetition rates and find a strong dependence on filament length and density depletion with repetition rate. Our analysis reveals the emergence of a significant stationary density depletion at repetition rates of 40 and 100 kHz. The corresponding reduction in the breakdown threshold by increasing the laser repetition rate observed in our study signifies a promising avenue for enhancing the efficiency and reliability of electric discharge triggering in various scenarios. Using capacitive plasma probe measurements, we address the limitations of fluorescence imaging-based measurements and demonstrate a systematic underestimation of filament length. This work contributes to a deeper understanding of the interplay between laser repetition rates, filamentation, and heat-driven density depletion effects from high-repetition-rate high-power laser systems and will contribute to guiding future research, making use of filaments at high repetition rates.

Long-lasting decreased pain threshold negatively affects functional recovery after arthroscopic rotator cuff repair.

The relationship between sensitization and postoperative function in patients undergoing arthroscopic rotator cuff repair (ARCR). The purpose of this study was to evaluate the effect of pre-and postoperative reductions in the pressure pain threshold (PPT) on postoperative clinical outcomes in patients with ARCR and investigate changes in PPT and clinical outcomes resulting from postoperative administration of weak opioids activating the central inhibitory system. This retrospective study included patients who underwent primary ARCR, categorized into Group A (excellent/good Constant scores) and B (fair/poor Constant scores). In a complementary study, patients were randomized to the Control or Tramadol groups. Both studies evaluated the PPT, visual analog scale, active range of motion (ROM), Constant score, and retear rates pre-and postoperatively. In the primary study with 158 patients, those with poor clinical outcomes exhibited significantly lower PPT at the affected shoulder preoperatively at 3months postoperatively compared to those with good outcomes. The PPT of the affected side was lower than that of the uninvolved side not only at 1 and 3 months but also preoperatively and at 6 months in the poor outcome group. In the secondary study involving 96 patients, weak opioid administration was associated with increased PPT for 3 months, improved ROM at 3 months postoperatively, and reduced postoperative pain 1 year postoperatively. Patients experiencing poor postoperative clinical outcomes exhibited prolonged lowered PPT. Lowered PPT due to sensitization may adversely affect functional recovery and pain perception. Elevating PPT using weak opioids improved clinical outcomes during the acute perioperative period after ARCR. III.

Electrically evoked compound action potential in children following cochlear implantation and its correlation with cochlear nerve diameter

Background: The study evaluated changes in the threshold of ECAP recorded during cochlear implantation, at switch on, after three months and six months following cochlear implantation. It further assessed the correlation between the ECAP threshold with T and C levels and the cochlear nerve diameter measured preoperatively. Methods: A prospective study of 42 prelingually deaf children who underwent cochlear implantation was conducted. The ECAP threshold values intra-operatively, at switch on, three months and six months were recorded and analysed. The T and C levels were assessed six months postoperatively, and correlation with the ECAP threshold was analysed. The diameter of the cochlear nerve was recorded, and its correlation with the ECAP threshold was determined. Results: Over six months, the basal, central and apical electrodes showed a statistically significant reduction in ECAP threshold of 11.64%, 4.67% and 25.81%, respectively, in candidates implanted with Advanced Bionics implant and 18.89%, 12.78% and 14.08%, respectively in candidates implanted with Nucleus implant. The ECAP thresholds were lower for the apical electrodes. No correlation was found between the ECAP threshold and T and C levels. A correlation between the cochlear nerve diameter and ECAP was not statistically significant. Conclusions: There was a statistically significant change in the ECAP threshold over six months. There was no statistically significant correlation between the ECAP thresholds and T and C levels. The value of ECAP thresholds to measure C and T values need to be relooked. There was no correlation between the cochlear nerve diameter and the ECAP threshold.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats.

To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

O057 The Impact of Surgical Weight Loss on the Physiological Endotypes causing Obstructive Sleep Apnea

Abstract Background Weight loss improves upper airway collapsibility in people with obstructive sleep apnoea (OSA). However, it’s unclear how weight loss affects the other endotypes responsible for OSA (loop gain, arousal threshold and muscle compensation). We investigated the effect surgical weight loss has on the OSA endotypes and whether the baseline endotypes predict response to surgery. Methods Endotypes were measured using non-invasive methods in 43 OSA patients who had a clinical polysomnogram before and after (~6-18 months) receiving weight loss surgery. Linear regression was used to assess whether the baseline endotypes predicted improvement in OSA severity defined by the apnoea-hypopnoea index (AHI). Results Weight loss surgery was associated with significant improvements in AHI (43.4[28.6-64.8]events/hr vs. 16.9[11.6-33.3]events/hr, p&amp;lt;0.001), body mass index (42.1 ±5.5kg/m2 vs. 32.8 ±4.5kg/m2, p&amp;lt;0.001), upper airway collapsibility (73.8[65.2-78.5]%eupnea vs. 77.1[71.7-81.3]%eupnea, p=0.034) and loop gain (0.62[0.53-0.71] vs. 0.54[0.44-0.72], p=0.012). Weight loss surgery was also associated with a reduced arousal threshold (144.5[130.1-160.5] vs.136.9[121.9-156.4], p=0.007). A greater reduction in OSA severity was associated with greater improvements in upper airway collapsibility (p=0.001, r2 =0.23) and reductions in the arousal threshold (p&amp;lt;0.001, r2=0.27). Poor upper airway collapsibility at baseline was weakly predictive of a greater improvement in OSA severity (p=0.018, r2 =0.13). No other endotype was predictive of OSA improvement. Discussion Weight loss surgery is associated with improvements in weight, OSA severity, upper airway collapsibility and loop gain. There was a paradoxical worsening of arousal threshold. Furthermore, weight loss surgery may be particularly effective in improving OSA in those with poor upper airway collapsibility.

Investigation of Optical Cavity Dynamics with Raman and Ytterbium-Doped Gain Media Integration

This study delves into a comprehensive examination of an optical cavity system that integrates Raman and Yb-doped gain media, with a focus on understanding their interactions. The research implies a characterization of each gain medium within the cavity while subjecting them to diverse co-pumping conditions with the other. When the Raman-lasing cavity is co-pumped by exciting the Yb-doped section, the resulting composite laser exhibits significant threshold reductions and there is an optimal co-pumping regime that enhances energy transfer from pump to Stokes. As for the complementary cavity, where the Yb-doped gain is influenced by the co-pumped Raman gain, at moderate pump powers a light-controlling-light behavior phenomenon arises. Within this regime, the 1064 nm signal suppresses the Yb-generated 1115 nm signal, suggesting potential applications in intracavity optical modulation. For higher pump levels, a cooperative effect emerges whereby both lasers mutually enhance each other. Minor variations in the primary 974 nm pump power, even by just a few milliwatts, result in significant capabilities for switching or modulating the Stokes signal. Under these conditions of mutual enhancement, the hybrid optical system validates notable improvements regarding energy transfer efficiency and threshold reduction. This research provides valuable insights into the intricate dynamics of optical cavity systems and reveals promising avenues for applications in advanced optical modulation technologies.

Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice.

Sigma-1 receptors (σ1Rs) are implicated in nociception, including pain sensitization, and inflammation. We assessed the role of σ1Rs on acute colitis-associated hypersensitivity using both genetic (constitutive knockout) and pharmacological blockade of the receptor. Colitis was induced in CD1 wild-type (WT) and σ1R KO mice (exposure to dextran sodium sulfate, 3%). A von Frey test was used to assess referred mechanosensitivity (abdominal and plantar withdrawal responses). The effects of the selective σ1R antagonists BD1063 and E-52862 were also assessed in WT animals. The expression of immune and sensory-related markers (RT-qPCR, Western blot) was assessed in the colon and lumbosacral spinal cord. The genetic ablation or pharmacological blockade of σ1Rs attenuated acute colonic inflammation in a similar manner. Mechanosensitivity was similar in WT and σ1R KO mice before colitis. In WT mice, but not in σ1R KO, colitis was associated with the development of referred mechanical hypersensitivity, manifested as a reduction in the withdrawal thresholds to mechanical probing (paw and abdominal wall). In WT mice, BD1063 and E-52862 blocked colitis-associated hypersensitivity. A genotype- and treatment-related differential regulation of sensory-related markers was detected locally (colon) and within the spinal cord. σ1Rs are involved in the development of acute intestinal inflammation and its associated referred mechanical hypersensitivity. The selective modulation of sensory-related pathways within the colon and spinal cord might be part of the underlying mechanisms. These observations support the pharmacological use of σ1R antagonists for the treatment of intestinal inflammation-induced hypersensitivity.

Cavity Lasing Characteristics of Thioflavin T and Thioflavin X in Different Solvents and Their Interaction with DNA for the Controlled Reduction of a Light Amplification Threshold in Solid-State Biofilms.

The lasing characteristics of Thioflavin T (ThT) and Thioflavin X (ThX) dyes were investigated in solvents with increasing viscosity: water, ethanol, butanol, ethylene glycol, and glycerol and three forms of DNA (double-helix natural, fragmented, and aggregated). The results identified that lasing thresholds and photostability depend on three critical factors: the solvation shell surrounding dye molecules, the organization of their dipole moments, which is driven by the DNA structure, and the molecules diffusion coefficient in the excitation focal spot. The research highlights that dye doped to DNA accumulated in binding sites fosters long-range dye orientation, facilitating a marked reduction of lasing thresholds in the liquid phase as well as amplified spontaneous emission (ASE) thresholds in the solid state. Leveraging insights from lasing characteristics obtained in liquid, ASE in the solid state was optimized in a controlled way by changing the parameters influencing the DNA structure, i.e., magnesium salt addition, heating, and sonication. The modifications led to a large decrease in the ASE thresholds in the dye-doped DNA films. It was shown that the examination of lasing in cavities can be useful for preparing optical materials with improved architectures and functionalities for solid-state lasers.

Progesterone Receptor Activation Regulates Sensory Sensitivity and Migraine Susceptibility

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to mechanical stimulus during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. Progesterone treatment of ovariectomized and estrogen-primed mice caused a delayed reduction in the mechanical threshold. Segesterone, a specific agonist of PRs replicated this effect, whereas, the segesterone-induced reduction in mechanical threshold was blocked in the mice lacking PRs in the nervous system. Segesterone treatment also did not alter mechanical threshold in adult male and juvenile female mice. PR activation increased the cold sensitivity but did not affect the heat and light sensitivity. We evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin when administered sequentially, reduced the pain threshold but not when given separately. PRs were expressed in several components of the migraine ascending pain pathway, and their deletion blocked the painful effects of nitroglycerin. PR activation also increased the number of active neurons in the components of the migraine ascending pain pathway. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain and migraine in women. PerspectiveThis article provides evidence for the role of progesterone receptors in regulating pain sensitivity and migraine susceptibility in females. Progesterone receptors may be a therapeutic target to treat chronic pain conditions more prevalent in women than men.

On the origin of the DIII-D L-H power threshold isotope effect

The increased low to high confinement mode (L to H-mode) power threshold PLH in DIII-D low collisionality hydrogen plasmas (compared to deuterium) is shown to result from lower impurity (carbon) content, consistent with reduced (mass-dependent) physical and chemical sputtering of graphite. Trapped gyro-Landau fluid (TGLF) quasilinear calculations and local non-linear gyrokinetic CGYRO simulations confirm stabilization of ion temperature gradient (ITG) driven turbulence by increased carbon ion dilution as the most important isotope effect. In the plasma edge, electron non-adiabaticity is also predicted to contribute to the isotope dependence of thermal transport and PLH , however its effect is subdominant compared to changes from impurity isotopic behavior. This L-H power threshold reduction with increasing carbon content at low collisionality is in stark contrast to high collisionality results, where additional impurity content appears to increase the power necessary for H-mode access.