Evidence for a role of NTS2 receptors in the modulation of tonic pain sensitivity

<p>Abstract</p> <p>Background</p> <p>Central neurotensin (NT) administration results in a naloxone-insensitive antinociceptive response in animal models of acute and persistent pain. Both NTS1 and NTS2 receptors were shown to be required for different aspects of NT-induced analgesia. We recently demonstrated that NTS2 receptors were extensively associated with ascending nociceptive pathways, both at the level of the dorsal root ganglia and of the spinal dorsal horn. Then, we found that spinally administered NTS2-selective agonists induced dose-dependent antinociceptive responses in the acute tail-flick test. In the present study, we therefore investigated whether activation of spinal NTS2 receptors suppressed the persistent inflammatory pain symptoms observed after intraplantar injection of formalin.</p> <p>Results</p> <p>We first demonstrated that spinally administered NT and NT69L agonists, which bind to both NTS1 and NTS2 receptors, significantly reduced pain-evoked responses during the inflammatory phase of the formalin test. Accordingly, pretreatment with the NTS2-selective analogs JMV-431 and levocabastine was effective in inhibiting the aversive behaviors induced by formalin. With resolution at the single-cell level, we also found that activation of spinal NTS2 receptors reduced formalin-induced <it>c-fos </it>expression in dorsal horn neurons. However, our results also suggest that NTS2-selective agonists and NTS1/NTS2 mixed compounds differently modulated the early (21–39 min) and late (40–60 min) tonic phase 2 and recruited endogenous pain inhibitory mechanisms integrated at different levels of the central nervous system. Indeed, while non-selective drugs suppressed pain-related behaviors activity in both part of phase 2, intrathecal injection of NTS2-selective agonists was only efficient in reducing pain during the late phase 2. Furthermore, assessment of the stereotypic pain behaviors of lifting, shaking, licking and biting to formalin also revealed that unlike non-discriminative NTS1/NTS2 analogs reversing all nociceptive endpoint behaviors, pure NTS2 agonists specifically inhibited paw lifting, supporting a role of NTS2 in spinal modulation of persistent nociception.</p> <p>Conclusion</p> <p>The present study provides the first demonstration that activation of NTS2 receptors produces analgesia in the persistent inflammatory pain model of formalin. The dichotomy between these two classes of compounds also indicates that both NTS1 and NTS2 receptors are involved in tonic pain inhibition and implies that these two NT receptors modulate the pain-induced behavioral responses by acting on distinct spinal and/or supraspinal neural circuits. In conclusion, development of NT agonists targeting both NTS1 and NTS2 receptors could be useful for chronic pain management.</p

Etude d'empilements multicouches colloidaux préparés par voie sol-gel (propriétés optiques et mécaniques)

Les procédés de dépôt de couches minces optiques par voie physique ou par voie sol-gel présentent par nature des limitations pour la réalisation de revêtements épais (>1 m) et ont alors recours à des empilements multicouches pour la préparation de miroirs diélectriques ou de polariseurs. C'est pour ces raisons qu'il est intéressant d'étudier les conditions permettant d'augmenter l'épaisseur critique des films sol-gel notamment. Après avoir étudié la capacité d'empilements des couches colloïdales, trois principaux paramètres ont été identifiés permettant d'augmenter l'épaisseur critique d'empilements monomatériaux et multimatériaux. Ces paramètres sont : l'épaisseur déposée,les interactions chimiques entre les particules et le temps de séchage du film. Ils influencent la microstructure des empilements et par conséquent les propriétés optiques et mécaniques. En contrôlant tous ces paramètres, nous avons montré qu'il est possible de préparer des empilements colloïdaux de fortes épaisseurs ouvrent la voie à la préparation sol-gel de miroirs de hautes performances et/ou de polariseurs. En outre, un développement spécifique de méthodes de caractérisations optiques et mécaniques a été nécessaire pour l'étude de ces films sol-gel, à la fois minces et fragiles.Main optical deposition processes, physical vapor deposition or sol-gel, exhibit difficulties of achieving thick coatings (>1 m) and to build multilayer stacks (dielectric mirrors, polarizers). For these reasons, we have studied the conditions to enable a significative increase of deposited sol-gel films thickness. Three main parameters have been evidenced enabling the control of the stacking ability : single layer deposited thickness, chemical interactions beetween nanoparticles and coating drying time. We have shown that these parameters depend on the sol composition and on deposition conditions (process) and that the microstructure of single material stacking is influenced. Optical and mechanical properties of sol-gel films have been studied and optimized regarding these different material and process parameters. For this reason, optical and mechanical characterization techniques have been specifically developed and can now be used for fragile and thin film characterization. In controlling all these parameters, it is now possible to prepare multilayer colloidal stack with high thicknesses enabling the fabrication of high-performance mirrors and polarizers.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

A tale of resilience: On the practical security of masked software implementations

International audienceMasking constitutes a provably-secure approach against side-channel attacks. However, recombination effects(e.g., transitions) severely reduce the proven security. Concerning the software domain, CPU microarchitectures encompass techniques improving the execution performances. Several studies show that such techniques induce recombination effects. Furthermore, these techniques implicitly induce some form of parallelism, and the potential associated threat has never been investigated. In addition, the practicalsecurity of masking relies on the chosen masking scheme. Few works analysed the security of software protected by different masking schemes, and none considered the parallelism threat. Thus, literature lacks of a more comprehensive investigation on the practical security of software implementations relying on various masking schemes in presence of micro-architecture-induced recombination effects and parallelism. This work performs a first step to fill this gap. Specifically, we evaluate the practical security offered by first-order Boolean, arithmetic-sum and inner-product masking against transitions and parallelism in software. We firstly assess the presence of transition and parallel-based leakages in software. Secondly, we evaluate the security of the encodings of the selected masking schemes with respect to each leakage source via micro-benchmarks. Thirdly, we assess the practical security of different AES-128 software implementations, one for each selected masking scheme. We carry out the investigation on the STM32F215 and STM32F303 micro-controllers. We show that (1) CPU’s parallel features allow successful attacks against masked implementations resistant to transition-based leakages; (2) implementation choices (e.g., finite field multiplication) impact on the practical security of masked software implementations in presence of recombination effects

Automated Software Protection for the Masses Against Side-Channel Attacks

International audienceWe present an approach and a tool to answer the need for effective, generic, and easily applicable protections against side-channel attacks. The protection mechanism is based on code polymorphism, so that the observable behaviour of the protected component is variable and unpredictable to the attacker. Our approach combines lightweight specialized runtime code generation with the optimization capabilities of static compilation. It is extensively configurable. Experimental results show that programs secured by our approach present strong security levels and meet the performance requirements of constrained systems

PROSECCO: Formally-proven secure compiled code

International audienceThe application and the verification of countermeasures against physical attacks still remainlong, error-prone and expertise-demanding tasks. We propose a toolchain to help the expertin these tasks. Our toolchain is composed of two components: a compiler that automaticallyapplies a set of countermeasures, and a formal verification tool that automatically verifiesbinary code for various leakage models and fault models. We describe different scenarios ofusage of our toolchain, and then illustrate the flexibility of our toolchain in one of them.L’application et la vérification de contre-mesures contre les attaques physiques sont des tâches qui sont longues, qui comportent un important risque d’erreur, et qui demandent une forte expertise. Nous proposons une chaîne d’outils pour aider les experts dans ces tâches. Notre chaîne d’outils se décompose en deux élements : un compilateur capable d’appliquer automatiquement différentes contremesures contre les attaques en fautes ou par canal auxiliaire, et un outil de vérification formelle dont le but est de vérifier automatiquement la robustesse des codes binaires en considérant des modèles de fuites et de fautes variés. Nous décrivons plusieurs scénarios d’utilisation de notre chaîne d’outils, et illustrons la flexibilité de celle-ci sur un de ces scénarios

PROSECCO: Formally-proven secure compiled code

International audienceThe application and the verification of countermeasures against physical attacks still remainlong, error-prone and expertise-demanding tasks. We propose a toolchain to help the expertin these tasks. Our toolchain is composed of two components: a compiler that automaticallyapplies a set of countermeasures, and a formal verification tool that automatically verifiesbinary code for various leakage models and fault models. We describe different scenarios ofusage of our toolchain, and then illustrate the flexibility of our toolchain in one of them.L’application et la vérification de contre-mesures contre les attaques physiques sont des tâches qui sont longues, qui comportent un important risque d’erreur, et qui demandent une forte expertise. Nous proposons une chaîne d’outils pour aider les experts dans ces tâches. Notre chaîne d’outils se décompose en deux élements : un compilateur capable d’appliquer automatiquement différentes contremesures contre les attaques en fautes ou par canal auxiliaire, et un outil de vérification formelle dont le but est de vérifier automatiquement la robustesse des codes binaires en considérant des modèles de fuites et de fautes variés. Nous décrivons plusieurs scénarios d’utilisation de notre chaîne d’outils, et illustrons la flexibilité de celle-ci sur un de ces scénarios

Maskara: Compilation of a Masking Countermeasure with Optimised Polynomial Interpolation

International audienceSide-channel attacks are amongst the major threats for embedded systems and IoT devices. Masking is one of the most used countermeasure against such attacks, but its application remains a difficult process. We propose a target-independent approach for applying a first-order boolean masking countermeasure during compilation, on the static single assignment form. Contrary to state-of-the art automated approaches that require to simplify the control flow of the input program, our approach supports regular control-flow program structures. Moreover, our compiler is the first to automatically mask table lookups using a polynomial interpolation approach. We also present new optimisations to speed up the evaluation of polynomials: we reduce the number of terms of the polynomial, and we accelerate finite field multiplication. We show that our approach is faster than the standard masked table approach with mask refresh after each access, with speedups up to ×2.4 in our experiments. Finally, using a formal verification approach, we show that the compiled machine code is secure, i.e., that all intermediate computations are statistically independent of the secrets

Indentation hardness and scratch tests for thin layers manufactured by sol-gel process

International audienceWe introduce our first tests to characterize the mechanical properties of elastic layer manufactured by sol-gel process obtained with an indenter designed from a microscope. They are performed with a microscope and a diamond ti