Thermal Stimuli Research Articles

Coadministration of Novel Analgesic Isovaline with Tramadol Reduces Inflammatory Pain Response in Rats

Aim: Isovaline is a new and promising analgesic with an antinociceptive effect and, unlike µ-opioid agonists, interacts with aminobutyric acid receptors without causing sedation or respiratory depression. In this study, we compare the effect on thermal hyperalgesia and mechanical allodynia coadministration of subcutaneous isovaline and tramadol with individual administrations in a carrageenan-induced hind paw inflammatory pain model in rats. Methods: In this study, isovaline, tramadol, and the combination of isovaline and tramadol were subcutaneously administered to rats with carrageenan-induced inflammation of the hind paws. Hyperalgesia in response to thermal stimuli and allodynia in response to mechanic stimuli were assessed by using a thermal plantar test and a dynamic plantar aesthesiometer, respectively. Results: The administration of subcutaneous isovaline 400mg/kg and tramadol 4mg/ kg combination effect was higher than the other groups on latencies and thresholds (P

Synergistic Thermal and Electron Wind Force-Assisted Annealing for Extremely High-Density Defect Mitigation.

This study investigates the effectiveness of combined thermal and athermal stimuli in mitigating the extremely high-density nature of dislocation networks in the form of low-angle grain boundaries in FeCrAl alloy. Electron wind force, generated from very low duty cycle and high current density pulses, was used as the athermal stimulus. The electron wind force stimulus alone was unable to remove the residual stress (80% low-angle grain boundaries) due to cold rolling to 25% thickness reduction. When the duty cycle was increased to allow average temperature of 100 °C, the specimen could be effectively annealed in 1 min at a current density of 3300 A/mm2. In comparison, conventional thermal annealing requires at least 750 °C and 1.5 h. For specimens with 50% thickness reduction (85% low-angle grain boundaries), the electron wind force was again unable to anneal the defects even at 3300 A/mm2 current density and average temperature of 100 °C. Intriguingly, allowing average concurrent temperature of 200 °C eliminated almost all the low-angle grain boundaries at a current density of 700 A/mm2, even lower than that required for the 25% thickness reduced specimens. Comprehensive electron and X-ray diffraction evidence show that alloys with extremely high defect density can be effectively annealed in less than a minute at approximately 200 °C, offering a substantial improvement over conventional high-temperature annealing.

Uncovering Temperature-Insensitive Feature of Phase Change Thermal Storage Electrolyte for Safe Lithium Battery.

Lithium-ion batteries (LIBs) have emerged as highly promising energy storage devices due to their high energy density and long cycle life. However, their safety concern, particularly under thermal shock, hinders their widespread applications. Herein, a temperature-insensitive electrolyte (TI-electrolyte) with exceptional resistance to thermal stimuli is presented to address the safety issues arising from the lack of thermal abuse tolerance in LIBs. The TI-electrolyte is composed of two phase-change polymers with differentiation melting points (60 and 35°C for polycaprolactone and polyethylene glycol respectively), delivering a wide temperature-resistant range. It is demonstrated that the TI-electrolyte possesses a heat capacity of 27.3Jg-1. The crystalline region in the TI-electrolyte shrinks when confronted with above-ambient temperature, absorbing heat to unlock molecular chains fixed in the crystal lattice, becoming amorphous. Notably, the Li||LFP pouch cell delays 3 valuable minutes to achieve the same temperature as conventional liquid electrolytes (LE) when subjected to thermal shocks, paralleling with the simulation results. Moreover, symmetrical Li||Li cell cycles stably for over 600h at 0.1mAcm-2, and Li||LFP full cell demonstrates excellent electrochemical performance, with a capacity of 142.7mAhg-1 at 0.5C, thus representing a critical approach to enhancing the safety of LIBs.

Microwave-Responsive Metal-Organic Frameworks (MOFs) for Enhanced In Vitro Controlled Release of Doxorubicin.

Metal-organic frameworks (MOFs) are excellent candidates for a range of applications because of their numerous advantages, such as high surface area, porosity, and thermal and chemical stability. In this study, microwave (MW) irradiation is used as a novel stimulus in vitro controlled release of Doxorubicin (DOX) from two MOFs, namely Fe-BTC and MIL-53(Al), to enhance drug delivery in cancer therapy. DOX was encapsulated into Fe-BTC and MIL-53(Al) with drug-loading efficiencies of up to 67% for Fe-BTC and 40% for MIL-53(Al). Several characterization tests, including XRD, FTIR, TGA, BET, FE-SEM, and EDX, confirmed both MOF samples' drug-loading and -release mechanisms. Fe-BTC exhibited a substantial improvement in drug-release efficiency (54%) when exposed to microwave irradiation at pH 7.4 for 50 min, whereas 11% was achieved without the external modality. A similar result was observed at pH 5.3; however, in both cases, the release efficiencies were substantially higher with microwave exposure (40%) than without (6%). In contrast, MIL-53(Al) exhibited greater sensitivity to pH, displaying a higher release rate (66%) after 38 min at pH 5.3 compared to 55% after 50 min at pH 7.4 when subjected to microwave irradiation. These results highlight the potential of both MOFs as highly heat-responsive to thermal stimuli. The results of the MTT assay demonstrated the cell viability across different concentrations of the MOFs after two days of incubation. This suggests that MOFs hold promise as potential candidates for tumor targeting. Additionally, the fact that the cells maintained their viability at different durations of microwave exposure confirms that the latter is a safe modality for triggering drug release from MOFs.

Investigation on thermally assisted optically stimulated luminescence signal in natural CaF2

In this work, thermally assisted OSL (TA-OSL) of natural fluorite was investigated, aiming to understand better the role of traps in both TL and OSL. TA-OSL is the luminescence simultaneously stimulated by light and heat; from this combination it is possible to access deeper traps in the analyzed material, that, in general, need more energy to be accessed. Irradiations were performed at room temperature using the Sr-90/Y-90 source incorporated in the TL/OSL reader at a dose rate of about 10 mGy/s. The optical stimulus was blue light at 470 nm. The dosimeters were also irradiated with X and gamma-rays of various energies (from 20 keV to 1.25 MeV) for comparing the energy dependence of the OSL and the TA-OSL signals. Residual TL curves were acquired after OSL readouts for checking trap participation in OSL emission. The OSL measurements were done at temperatures from 25 °C to 400 °C. For readout temperatures from 25 to ∼185 °C, decay curves were observed, and they were modeled by one stretched-exponential function, giving rise to a good fit to the experimental data. The dependence of the fitting parameter (β) on the photon energy was studied, and it was observed that β increases with the X-ray beam effective energy. The energy dependence of OSL signal is 1.5 times larger than that of TA-OSL signal, pointing to the reduction in energy dependence with the combination of thermal and optical stimuli. The total light emitted (TA-OSL + residual TL) is highly increased by the simultaneous stimulation by light and heat, indicating that light promotes charges to thermally active traps (phototransfer), and heat promotes charges to optically active traps, facilitating their release during illumination.

Multiresponsive Bilayer Hydrogel Actuator with Switchable Shape Morphing Capability and Visible Color/Fluorescence Change.

Bilayer hydrogels, endowed with multiresponsive and switchable color-changing properties, have garnered significant attention for bioinspired artificial intelligent materials. However, the design and fabrication of such hydrogels that can fully mimic the adaptation of the live organism, i.e., simultaneous changes in shape, fluorescent, and/or visible color, still remain significant challenges. Herein, a multiresponsive (e.g., temperature, salt, and pH) and multiadaptive (shape, fluorescent color, and visible color changes) hydrogel was fabricated by employing monomers featuring pH-responsive fluorescence 4-(2-(4-(dimethylamino) phenyl)-1-isocyanovinyl) phenol (DP) and switchable color-changing 4-(2-sulfethyl) -1-(4-vinylbenzyl) pyridinium betaine (VPES). The bilayer hydrogel comprises a temperature- and pH-responsive gel layer, poly(N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate), along with a pH-, temperature-, and salt-responsive gel layer, poly(acrylamide-co-2-(dimethylamino)ethyl methacrylate-co-VPES)@DP. Due to the opposite swelling/shrinking behavior between the two layers, the prepared hydrogel exhibits shape changes in response to thermal, salt, and pH stimuli, along with switchable fluorescent color and visible color change that originate from DP and polyVPES, respectively. Apart from multiresponsive behavior, this hydrogel also shows an excellent antifatigue property and high sensitivity, which makes it hold significant potential in many applications. We anticipate that this strategy to realize multiresponsive capability in this work can also inspire the design of the biomimetic smart materials.

Thermal stimuli response diphenylmethane diisocyanate‐based polyurethane elastomer via adjustable silicon‐induced distinctive microstructure

AbstractThe segment character of polyurethanes (PUs) determines the micromorphology and properties. The effective segment regulation can customize the favorable performance of PUs. Herein, silicon covalent‐modified polyurethanes (MPUs) were prepared by incorporating diphenylmethane diisocyanate (MDI) and diphenyl silanediol (DPSD) into PU molecules as hard segments via a two‐step method. Distinctive microphase separation structures from sheet morphology to radial sheet or withered flower‐like microdomain were formed by adjusting hydrogen bonding of hard segments and post‐treatment techniques. Thus, with the addition of DPSD in hard segments, the thermo‐optic responses for MPUs occurred due to the different microphase evolution under thermal effect. And with the further addition of DPSD, the effect of thermal stimuli on the transmittance gradually weakened. It was very clear that with increasing the temperature, the transmittance of MPUs showed a gradual increase owing to melting the microcrystals or destroying the ordered accumulation of hard segments. Meanwhile, the high mechanical properties were obtained, higher 15 times tensile strength and more than 100 times elastic modulus than those of pure PU as well as the excellent thermal stability. In sum, this study was of great significance for developing new functionalized PU materials.Highlights Polyurethanes were prepared by inducing modified silicon functionality. The distinctive microphase separation evolution of MPUs was found. Thermal stimuli responses showed a gradual decrease due to different structure. High mechanical properties and thermal stability were also obtained.

Cleavable azobenzene linkers for the design of stimuli-responsive materials.

The azo linkage (NN) is one of the very few functional groups in organic chemistry that exhibits sensitivity towards thermal, chemical, photochemical, and biological stimuli. Consequently, this property has given rise to a distinct class of responsive materials. For example, thermal sensitivity has led to generation of free radical initiators useful in curing and polymerization applications. Chemically-induced cleavage has aided the development of self-immolative polymers and reactive scaffolds for proteomics applications. Photo-isomerization capability has given rise to photo-responsive systems. Azobenzene cleavage in biologically reducing environments, such as that of the colon, and under tumor hypoxia conditions has led to diagnostic, therapeutic, and delivery materials. Such conditions have also allowed for control over formation (assembly) and disruption (disassembly) of micellar nanoparticles. The aim of this review article is to look beyond the prevalent photosensitivity aspect of the aromatic azo compounds and draw attention to the azo scission reaction as a trigger of the change in the structure and properties of organic materials. Thus, the main discussion begins with the mechanism of the reductive cleavage. Then, its application in the design of molecules that can be activated as drugs and fluorescent sensors, (nano)materials with potential to release active substances, and polymers with side-chain and main-chain self-immolative capacity is discussed. Finally, the status and future challenges in this field are discussed.

Evaluating the Antihyperalgesic Potential of Sildenafil-Metformin Combination and Its Impact on Biochemical Markers in Alloxan-Induced Diabetic Neuropathy in Rats.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot-cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

Phase-Directed Assembly of Triboelectric Nanopaper for Self-Powered Noncontact Sensing.

Noncontact sensing technology serves as a pivotal medium for seamless data acquisition and intelligent perception in the era of the Internet of Things (IoT), bringing innovative interactive experiences to wearable human-machine interaction perception networks. However, the pervasive limitations of current noncontact sensing devices posed by harsh environmental conditions hinder the precision and stability of signals. In this study, the triboelectric nanopaper prepared by a phase-directed assembly strategy is presented, which possesses low charge transfer mobility (1618 cm2 V-1 s-1) and exceptional high-temperature stability. Wearable self-powered noncontact sensors constructed from triboelectric nanopaper operate stably under high temperatures (200 °C). Furthermore, a temperature warning system for workers in hazardous environments is demonstrated, capable of nonintrusively identifying harmful thermal stimuli and detecting motion status. This research not only establishes a technological foundation for accurate and stable noncontact sensing under high temperatures but also promotes the sustainable intelligent development of wearable IoT devices under extreme environments.

Nanocellulose-based cobalt(II) coordinated malonic acid hybrid aerogels exhibiting reversible thermochromism and moisture sensor properties

The emergence of sustainable polymers and technologies has led to the development of innovative materials with minimal carbon emissions which find extensive applications in wearable electronics, biomedical sensors, and Internet of Things (IoT)-based monitoring systems. Nanocellulose which can be generated from abundant biomass materials has been widely recognized as a sustainable alternative for a diverse range of applications due to its remarkable properties and eco-friendly nature. By making use of the unique and easily accessible coordination transformation property of Co(II) ions and associated visible light absorption changes, we report a novel Co(II) cation-incorporated nanocellulose/malonic acid hybrid aerogel material that exhibits reversible thermochromism induced by thermal stimulus in the presence of atmospheric moisture. This effect is accentuated by the highly porous nature of the nanocellulose aerogel material we have developed. Besides the reversible thermochromic property which Co(II) ions exhibit, the metal ions act as very efficient reinforcing units contributing significantly to the structural stability and rigidity of the hierarchical aerogels by coordinative cross-linking through carboxylate moieties present in the TEMPO-oxidized cellulose nanofibers (TCNF) and additionally adding malonic acid to provide sufficient COO− for cross-linking. Thorough characterization and detailed investigation of as-prepared hybrid aerogels was conducted to evaluate their overall properties including reversible thermochromism and moisture sensor behaviour. Further, an Android mobile-based application was developed to demonstrate the real-world application of the aerogels for atmospheric humidity sensing.

Effective brain connectivity related to non-painful thermal stimuli using EEG

Understanding the brain response to thermal stimuli is crucial in the sensory experience. This study focuses on non-painful thermal stimuli, which are sensations induced by temperature changes without causing discomfort. These stimuli are transmitted to the central nervous system through specific nerve fibers and are processed in various regions of the brain, including the insular cortex, the prefrontal cortex, and anterior cingulate cortex. Despite the prevalence of studies on painful stimuli, non-painful thermal stimuli have been less explored. This research aims to bridge this gap by investigating brain functional connectivity during the perception of non-painful warm and cold stimuli using electroencephalography (EEG) and the partial directed coherence technique (PDC). Our results demonstrate a clear contrast in the direction of information flow between warm and cold stimuli, particularly in the theta and alpha frequency bands, mainly in frontal and temporal regions. The use of PDC highlights the complexity of brain connectivity during these stimuli and reinforces the existence of different pathways in the brain to process different types of non-painful warm and cold stimuli.

Calcium hydroxyapatite @ polydopamine core-shell microspheres for photothermal regulation of human gingival fibroblast behavior

Gingival recession, a common oral problem, often results in functional complications and aesthetic imperfections. Calcium hydroxyapatite (HA) microspheres, known for their fibroblast-activating properties, have been used for facial tissue augmentation. The photothermal conversion effect, which uses near-infrared (NIR) light to generate mild thermal stimuli, has been shown to enhance cellular activity and accelerate wound healing. In the current study, core-shell structured calcium hydroxyapatite @ polydopamine (HA@PDA) microspheres with biocompatibility and photothermal efficacy were synthesized to improve the treatment of gingival recession. Cellular experiments demonstrated that the behavior of human gingival fibroblasts (HGFs) and the polarization of macrophages are modulated by HA@PDA microspheres through photothermal conversion under 808 nm NIR irradiation. The implications of these findings suggest that photothermal HA@PDA microspheres may serve as a promising modality for gingival augmentation, offering a safe, non-invasive, effective, and sustainable treatment strategy.

Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma.

SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss-of-function mutations in SLURP1 lead to a rare autosomal recessive palmoplantar keratoderma (PPK), Mal de Meleda (MdM), which is characterized by diffuse, yellowish palmoplantar hyperkeratosis. Some individuals with MdM experience pain in conjunction with the hyperkeratosis that has been attributed to fissures or microbial superinfection within the affected skin. By comparison, other hereditary PPKs such as pachyonychia congenita and Olmsted syndrome show prevalent pain in PPK lesions. Two mouse models of MdM, Slurp1 knock-out and Slurp2X knock-out, exhibit robust PPK in all four paws. However, whether the sensory experience of these animals includes augmented pain sensitivity remains unexplored. In this study, we demonstrate that both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors in males and females. Anatomical analysis revealed slightly reduced glabrous skin epidermal innervation and substantial alterations in palmoplantar skin immune composition in Slurp2X knock-out mice. Primary sensory neurons innervating hindpaw glabrous skin from Slurp2X knock-out mice exhibit increased incidence of spontaneous activity and mechanical hypersensitivity both in vitro and in vivo. Thus, Slurp knock-out mice exhibit polymodal PPK-associated pain that is associated with both immune alterations and neuronal hyperexcitability and might therefore be useful for the identification of therapeutic targets to treat PPK-associated pain.

Gaps in our understanding of how vagal afferents to the small intestinal mucosa detect luminal stimuli.

Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents' terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection.

Detection and characterization of defects in the Brancacci Chapel wall paintings via holographic interferometry and microwave reflectometry

This paper evaluates the improvements in wall paintings diagnostic achievable by the synergistic combination of DHSPI, SIRT and MWR techniques. These innovative portable and non-destructive techniques for in-situ diagnostic were tested in laboratory on mock-ups mimicking the real conditions of wall painting defects (such as detachments, cavities and cracks), and on the frescoes painted by Masolino, Masaccio and Filippino Lippi (between 1422 and 1475) in the Brancacci Chapel in the church of Santa Maria del Carmine in Florence, Italy. This research activity was part of the Brancacci Chapel diagnostic and monitoring project, where the assessment of the state of conservation is a mandatory prerequisite for planning the subsequent restoration work. In common practice, restorers make the preliminary evaluation on the state of conservation of the wall paintings by visual and tactile inspection, without the use of any special scientific instrumentation. Cracks, cavities, lack of material, detachments, out-of-plumb and deformation of (non-)structural elements are reported in a condition report to document the state of conservation at a given point in time. In particular, the detachments are recognized by the tap test, but this is a discretionary and highly subjective method. Thus, there is a strong demand for the development of a portable and non-destructive approach that refines this preliminary survey with objective data. Here, we present the results produced by the combination of MWR (useful for the dimensional characterization of hidden defects in the wall) and DHSPI-SIRT to identify the extent of deformations induced by thermal stimulus, providing an objective confirmation of the preliminary investigation performed by restorers, in which the detachments were indicated as “stable”, “not very stable” and “unstable”, i.e., close to falling. The integrated use of these techniques in situ, supported by a laboratory study on ad-hoc prepared mock-ups, proved to be suitable for a quantitative evaluation of damage risk to guide restoration strategy accordingly.

Biomorph Soft Actuators with Tardigrade‐Like Resilience

AbstractTardigrades are the most resilient biospecies on Earth, capable of surviving extreme conditions including high temperatures, pressures, air deprivation, and exposure to noxious chemicals and radiation. The study here undertakes biomimicry of the remarkable adaptability of tardigrades by designing biomorph soft actuators (BSAs) that can endure these harsh environments. Unlike previous tardigrade‐inspired materials, which lacked a naturalistic interaction with their surroundings, the BSAs replicate the anatomical macrostructures and the non‐monotonic environmental resilience of tardigrades, especially their ability to adapt via dehydration and rehydration. Dual‐layer hydrogel spheres are employed with embedded fluid bubbles, creating cohesive yet non‐monolithic smart BSA structures. These structures exhibit high resilience to compressive, thermal, and radiation stimuli, achieved through thermoresponsive shape morphing driven by fluid balance. Their advanced capabilities are also demonstrated, such as driving a McKibben‐type artificial muscle and rapidly regenerating themselves from a state exposed to hazardous chemicals. Such versatile actuating biomorphs hold great promise for various autonomous applications, including soft robotic operations in aqueous effluents, deserts, polar regions, and outer space.

Active Fabrics With Controllable Stiffness for Robotic Assistive Interfaces.

Assistive interfaces enable collaborative interactions between humans and robots. In contrast to traditional rigid devices, conformable fabrics with tunable mechanical properties have emerged as compelling alternatives. However, existing assistive fabrics actuated by fluidic or thermal stimuli struggle to adapt to complex body contours and are hindered by challenges such as large volumes after actuation and slow response rates. To overcome these limitations, inspiration is drawn from biological protective organisms combining hard and soft phases, and active assistive fabrics consisting of architectured rigid tiles interconnected with flexible actuated fibers are proposed. Through programmable tessellation of target body shapes into architectured tiles and controlling their interactions by the actuated fibers, the active fabrics can rapidly transition between soft compliant configurations and rigid states conformable to the body (>350 times stiffness change) while minimizing the device volume after actuation. The versatility of these active fabrics is demonstrated as exosuits for tremor suppression and lifting assistance,as body armors for impact mitigation, and integration withelectrothermal actuators for smart actuation with convenient folding capabilities. This work offers a practical framework for designing customizable active fabrics with shape adaptivity and controllable stiffness, suitable for applications in wearable exosuits, haptic devices, and medical rehabilitation systems.

Characterization and validation of a spontaneous acute and protracted oxycodone withdrawal model in male and female mice

Opioid use disorder (OUD) is a serious health problem that may lead to physical dependence, in addition to affective disorders. Preclinical models are essential for studying the neurobiology of and developing pharmacotherapies to treat these problems. Historically, chronic morphine injections have most often been used to produce opioid-dependent animals, and withdrawal signs indicative of dependence were precipitated by administering an opioid antagonist. In the present studies, we have developed and validated a model of dependence on oxycodone (a widely prescribed opioid) during spontaneous withdrawal in male and female C57BL/6J mice. Dependence was induced by chronically administering oxycodone through osmotic minipumps at different doses for 7 days. Somatic withdrawal signs were measured after 3, 6, 24, and 48 h following minipump removal. Additionally, sensitivity to mechanical, thermal, and cold stimuli, along with anxiety-like behavior, were also measured. Our results indicated that spontaneous withdrawal following discontinuation of oxycodone produced an increase in total withdrawal signs after 60 and 120 mg/kg/day regimens of oxycodone administration. These signs were reversed by the administration of clinically approved medications for OUD. In general, both female and male mice showed similar profiles of somatic signs of spontaneous withdrawal. Spontaneous withdrawal also resulted in mechanical and cold hypersensitivity lasting for 24 and 14 days, respectively, and produced anxiety-like behaviors after 2 and 3 weeks following oxycodone removal. These results help validate a new model of oxycodone dependence, including the temporally distinct emergence of somatic, hyperalgesic, and anxiety-like behaviors, potentially useful for mechanistic and translational studies of opioid dependence.

Quantitative sensory testing for assessment of somatosensory function in children and adolescents: a scoping review.

Quantitative sensory testing (QST) refers to a group of noninvasive psychophysical tests that examine responses to a range of calibrated mechanical and thermal stimuli. Quantitative sensory testing has been used extensively in adult pain research and has more recently been applied to pediatric pain research. The aims of this scoping review were to map the current state of the field, to identify gaps in the literature, and to inform directions for future research. Comprehensive searches were run in 5 databases. Titles, abstracts, and full texts were screened by 2 reviewers. Data related to the study aims were extracted and analyzed descriptively. A total of 16,894 unique studies were identified, of which 505 were screened for eligibility. After a full-text review, 301 studies were retained for analysis. Date of publication ranged from 1966 to 2023. However, the majority of studies (61%) were published within the last decade. Studies included participants across the developmental trajectory (ie, early childhood to adolescence) and most often included a combination of school-age children and adolescents (49%). Approximately 23% of studies were conducted in healthy samples. Most studies (71%) used only one QST modality. Only 14% of studies reported using a standardized QST protocol. Quantitative sensory testing in pediatric populations is an emerging and rapidly growing area of pain research. Future work is needed using comprehensive, standardized QST protocols to harness the full potential that this procedure can offer to our understanding of pediatric pain.