Sustained pain-related depression of behavior: effects of intraplantar formalin and complete freund’s adjuvant on intracranial self-stimulation (ICSS) and endogenous kappa opioid biomarkers in rats

Background: Intraplantar administration of complete Freund's adjuvant (CFA) and formalin are two noxious stimuli commonly used to produce sustained pain-related behaviors in rodents for research on neurobiology and treatment of pain. One clinically relevant manifestation of pain is depression of behavior and mood. This study compared effects of intraplantar CFA and formalin on depression of positively reinforced operant behavior in an assay of intracranial self-stimulation (ICSS) in rats. Effects of CFA and formalin on other physiological and behavioral measures, and opioid effects on formalin-induced depression of ICSS, were also examined. Results: There were four main findings. First, consistent with previous studies, both CFA and formalin produced similar paw swelling and mechanical hypersensitivity. Second, CFA produced weak and transient depression of ICSS, whereas formalin produced a more robust and sustained depression of ICSS that lasted at least 14 days. Third, formalin-induced depression of ICSS was reversed by morphine doses that did not significantly alter ICSS in saline-treated rats, suggesting that formalin effects on ICSS can be interpreted as an example of pain-related and analgesic-reversible depression of behavior. Finally, formalin-induced depression of ICSS was not associated with changes in central biomarkers for activation of endogenous kappa opioid systems, which have been implicated in depressive-like states in rodents, nor was it blocked by the kappa antagonist norbinaltorphimine. Conclusions: These results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems. Electronic supplementary material The online version of this article (doi:10.1186/1744-8069-10-62) contains supplementary material, which is available to authorized users

The cosmic ray test of MRPCs for the BESIII ETOF upgrade

In order to improve the particle identification capability of the Beijing Spectrometer III (BESIII),t is proposed to upgrade the current endcap time-of-flight (ETOF) detector with multi-gap resistive plate chamber (MRPC) technology. Aiming at extending ETOF overall time resolution better than 100ps, the whole system including MRPC detectors, new-designed Front End Electronics (FEE), CLOCK module, fast control boards and time to digital modules (TDIG), was built up and operated online 3 months under the cosmic ray. The main purposes of cosmic ray test are checking the detectors' construction quality, testing the joint operation of all instruments and guaranteeing the performance of the system. The results imply MRPC time resolution better than 100$ps$, efficiency is about 98$\%$ and the noise rate of strip is lower than 1$Hz/$($scm^{2}$) at normal threshold range, the details are discussed and analyzed specifically in this paper. The test indicates that the whole ETOF system would work well and satisfy the requirements of upgrade

Neuropeptide Deficient Mice Have Attenuated Nociceptive, Vascular, and Inflammatory Changes in a Tibia Fracture Model of Complex Regional Pain Syndrome

BACKGROUND: Distal limb fracture in man can induce a complex regional pain syndrome (CRPS) with pain, warmth, edema, and cutaneous inflammation. In the present study substance P (SP, Tac1(−/−)) and CGRP receptor (RAMP1(−/−)) deficient mice were used to investigate the contribution of neuropeptide signaling to CRPS-like changes in a tibia fracture mouse model. Wildtype, Tac1(−/−), and RAMP1(−/−) mice underwent tibia fracture and casting for 3 weeks, then the cast was removed and hindpaw mechanical allodynia, unweighting, warmth, and edema were tested over time. Hindpaw skin was collected at 3 weeks post-fracture for immunoassay and femurs were collected for micro-CT analysis. RESULTS: Wildtype mice developed hindpaw allodynia, unweighting, warmth, and edema at 3 weeks post-fracture, but in the Tac1(−/−) fracture mice allodynia and unweighting were attenuated and there was no warmth and edema. RAMP1(−/−) fracture mice had a similar presentation, except there was no reduction in hindpaw edema. Hindpaw skin TNFα, IL-1β, IL-6 and NGF levels were up-regulated in wildtype fracture mice at 3 weeks post-fracture, but in the Tac1(−/−) and RAMP1(−/−) fracture mice only IL-6 was increased. The epidermal keratinocytes were the cellular source for these inflammatory mediators. An IL-6 receptor antagonist partially reversed post-fracture pain behaviors in wildtype mice. CONCLUSIONS: In conclusion, both SP and CGRP are critical neuropeptide mediators for the pain behaviors, vascular abnormalities, and up-regulated innate immune responses observed in the fracture hindlimb. We postulate that the residual pain behaviors observed in the Tac1(−/−) and RAMP1(−/−) fracture mice are attributable to the increased IL-6 levels observed in the hindpaw skin after fracture

Design monolayer iodinenes based on halogen bond and tiling theory

Xenes, two-dimensional (2D) monolayers composed of a single element, with graphene as a typical representative, have attracted widespread attention. Most of the previous Xenes, X from group-IIIA to group-VIA elements have bonding characteristics of covalent bonds. In this work, we for the first time unveil the pivotal role of a halogen bond, which is a distinctive type of bonding with interaction strength between that of a covalent bond and a van der Waals interaction, in 2D group-VIIA monolayers. Combing the ingenious non-edge-to-edge tiling theory and state-of-art ab initio method with refined local density functional M06-L, we provide a precise and effective bottom-up construction of 2D iodine monolayer sheets, iodinenes, primarily governed by halogen bonds, and successfully design a category of stable iodinenes, encompassing herringbone, Pythagorean, gyrated truncated hexagonal, i.e. diatomic-kagome, and gyrated hexagonal tiling pattern. These iodinene structures exhibit a wealth of properties, such as flat bands, nontrivial topology, and fascinating optical characteristics, offering valuable insights and guidance for future experimental investigations. Our work not only unveils the unexplored halogen bonding mechanism in 2D materials but also opens a new avenue for designing other non-covalent bonding 2D materials.Comment: 6 pages, 4 figure

Effects of Purple Rice and Morchella esculenta Powder Substitution on the Quality of Dough and Bread

In order to meet people's demand for diversified and functional bread products, the effects of wheat flour substituted with purple rice (0, 3%, 6%, 9%, and 12%) and Morchella esculenta (0 and 3%) powder on the rheological behavior of dough, dietary fiber content, baking attributes of bread, starch digestibility in vitro, and volatile flavor compounds were investigated. The results indicated that the substitution of purple rice and Morchella esculenta powder enhanced the storage modulus and loss modulus of dough, while the \begin{document}$\mathrm{tan}\delta$\end{document} value exhibited a gradual decline. Substitution of purple rice and Morchella esculenta powder elevated the dietary fiber content of bread, while decreasing the specific volume, elasticity, and cohesion of bread, and significantly (P<0.05) increasing the hardness and chewiness of bread. When the Morchella esculenta powder substitution content maintained was 3%, the content of purple rice powder was in the range from 0 to 12%, the L* value of bread crust and crumb gradually decreased and the ΔE value gradually increased, resulting in a darker color when compared to control group. The substitution of purple rice and Morchella esculenta powder decelerated the starch hydrolysis rate of bread. The electronic nose test revealed that the flavor substances were mainly alcohols, aromatics, aliphatic hydrocarbons, and esters, and the bread was rich in flavor. Therefore, the appropriate partial substitution with purple rice and Morchella esculenta powder could effectively improve the quality and characteristics of bread, and provided a useful reference for the development of functional bread

Preferential Multi-Objective Bayesian Optimization

Preferential Bayesian optimization (PBO) is a framework for optimizing a decision-maker\u27s latent preferences over available design choices. While preferences often involve multiple conflicting objectives, existing work in PBO assumes that preferences can be encoded by a single objective function. For example, in robotic assistive devices, technicians often attempt to maximize user comfort while simultaneously minimizing mechanical energy consumption for longer battery life. Similarly, in autonomous driving policy design, decision-makers wish to understand the trade-offs between multiple safety and performance attributes before committing to a policy. To address this gap, we propose the first framework for PBO with multiple objectives. Within this framework, we present dueling scalarized Thompson sampling (DSTS), a multi-objective generalization of the popular dueling Thompson algorithm, which may be of interest beyond the PBO setting. We evaluate DSTS across four synthetic test functions and two simulated exoskeleton personalization and driving policy design tasks, showing that it outperforms several benchmarks. Finally, we prove that DSTS is asymptotically consistent. As a direct consequence, this result provides, to our knowledge, the first convergence guarantee for dueling Thompson sampling in the PBO setting