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Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution.
Learn More >Osteoarthritis (OA) is a multidimensional health problem and a common chronic disease. It has a substantial impact onpatient quality of life and is a common cause of pain and mobility issues in older adults. The functional limitations, lack of curative treatments, and cost to society all demonstrate the need for translational and clinical research. The use of OA models in mice is important for achieving a better understanding of the disease. Models with clinical relevance are needed to achieve 2 main goals: to assess the impact of the OA disease (pain and function) and to study the efficacy of potential treatments. However, few OA models include practical strategies for functional assessment of the mice. OA signs in mice incorporate complex interrelations between pain and dysfunction. The current review provides a comprehensive compilation of mousemodels of OA and animal evaluations that include static and dynamic clinical assessment of the mice, merging evaluationof pain and function by using automatic and noninvasive techniques. These new techniques allow simultaneous recordingof spontaneous activity from thousands of home cages and also monitor environment conditions. Technologies such as videographyand computational approaches can also be used to improve pain assessment in rodents but these new tools must first be validated experimentally. An example of a new tool is the digital ventilated cage, which is an automated home-cage monitor that records spontaneous activity in the cages.
Learn More >In a study recently published by our research group, the compounds isoxazoline-acylhydrazone derivatives R-99 and R-123 presented promising antinociceptive activity. However, the mechanism of action of this compound is still unknown.
Learn More >In rodents, morphine antinociception is influenced by sex. However, conflicting results have been reported regarding the interaction between sex and morphine antinociceptive tolerance. Morphine is metabolised in the liver and brain into morphine-3-glucuronide (M3G). Sex differences in morphine metabolism and differential metabolic adaptations during tolerance development might contribute to behavioural discrepancies. This article investigates the differences in peripheral and central morphine metabolism after acute and chronic morphine treatment in male and female mice.
Learn More >Whether pinocembrin (PCN) could be utilized to alleviate hip fracture-induced pain is investigated in this research. Aged rats with hip fractures were treated with vehicle or 80 mg/kg/day PCN from week 3 to week 4. Then hind paw mechanical allodynia, unweighting, warmth, and thickness were measured. The microglia and astrocytes activation and proliferation markers in the spinal dorsal horn were detected with real-time PCR and immunofluorescence staining. The relative expression of substance P and its receptor, tachykinin receptor 1 (Tacr1), were detected with enzyme-linked immunosorbent assay (ELISA) and Western blots. The antinociceptive effect of Tacr1 inhibitor LY303870 was also testified. PCN alleviated hip fracture-induced hind paw nociceptive (allodynia and unweighting) and vascular changes (warmth and thickness) in aged rats with diminished microglia and astrocytes activation and proliferation in the spinal dorsal horn. Up-regulated substance P and Tacr1 were induced after hip fracture, which could be reversed by PCN treatment. Furthermore, LY303870 treatment partially reversed both spinal nociceptive sensitization and vascular changes after hip fracture. Substance P signaling contributes to the nociceptive and vascular changes observed in the hip fracture, which could be alleviated by PCN.
Learn More >The aim of this study was to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and high-intensity laser therapy (HILT), as outpatient physical therapy modalities, on knee osteoarthritis (KOA) patients. The treatment program was completed by 40 individuals with stage II KOA (according to Kellgren and Lawrence) who were randomly allocated to one of two groups. They have had more than grade 3 pain on the visual analog scale (VAS) during activities for the last 3 months, with body-mass index less than 30 and no history of knee operation, fracture, cancer, or other neuromuscular or musculoskeletal diseases that may affect study results. The ESWT group ( = 20, mean age = 40.12 ± 9.45 years) received ESWT, 0.05 mJ/mm, one session/week for 4 weeks, and the HILT group ( = 20, mean age = 46.62 ± 8.68 years) received HILT, 1500 mJ/cm in each session, three sessions/week for 4 weeks. Both groups received conservative physical therapy programs. Before and after 4 weeks of intervention, pain, physical function, and disability were assessed using a VAS, 6-min walking test, and the Western Ontario and McMaster Universities Osteoarthritis Index. When the pre- and post-treatment mean values of dependent variables of both groups were compared, there were statistically significant improvements in both groups. Significant differences in the measured variables were also discovered in favor of the HILT group compared with the ESWT group. HILT showed a superior effect compared with ESWT on pain, physical function, and disability in chronic KOA patients. Pan African Clinical Trials Registry number: PACTR202007638955907.
Learn More >Migraine is one of the most common neurological disorders associated with recurrent attacks of moderate to severe headache. Oxidative stress may play an important role in migraine pathogenesis. This study aimed to measure and compare the serum levels of Selenium, total antioxidant capacity (TAC), and malondialdehyde) MDA (in migraine patients and healthy individuals. This case-control study was performed on 31 migraine patients and 30 age and gender-matched healthy controls. The severity of headache was assessed with a standard questionnaire, and the serum levels of Selenium (Se), MDA, and TAC were measured via biochemical methods. The odds of migraine were calculated across quartile of Se and oxidative stress biomarkers via binary logistic regression. Migraine patients had a significant lower Se levels (81.06 ± 8.66 vs. 88.94 ± 10.23 μg/L, P = 0.002) and a significant higher MDA levels (3.04 ± 1.74 vs. 2.06 ± 0.59 nmol/ml, P = 0.005) compared to healthy participants. Although serum TAC levels (1.34 ± 0.34 vs.1.37 ± 0.33 mmol/L, P = 0.755) were not significantly different between migraine patients rather than healthy subjects. Individuals in the lowest quartile of Se levels were about eleven times more likely to have migraine than those in the highest quartile (OR: 11.2; 95%CI: 1.57 to 80.2; P-trend: 0.016). Besides, being in the highest quartile of the serum MDA level, the odds of having migraine increases 15.4 times compared to the lowest quartile (OR = 15.4, 95%CI: 1.1 to 221, P = 0.044). No significant association was found between TAC and migraine. The lower Se and MDA levels in migraine patients gives rise to the probability which oxidant status may play an underlying role in migraine pathophysiology.
Learn More >Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal models.Mouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively. Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50 °C and 4 °C respectively) and mechanical pain (von Frey test) tests after intraperitoneal (i.p.) administration of asprosin (10 µg/kg) and gabapentin (50 mg/kg) in several times intervals. Besides, possible effect of asprosin on the motor coordination of mice was assessed with a rotarod test. Serum level of asprosin was quantified by ELISA.In neuropathic pain models (STZ, OXA, and CCI), asprosin administration significantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. The most effective time of asprosin on pain threshold was observed 60 min after its injection. Also, asprosin displayed no notable effect on the motor activity. Asprosin levels were significantly lower in neuropathic pain compared to healthy group (p < 0.05).The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.
Learn More >Pressure pain threshold (PPT) is a widely applied method for measuring the magnitude of increased peripheral and central pain sensitivity causing hyperalgesia in knee osteoarthritis (OA). Although manual therapy techniques effects positively PPT, the effect of end-range Maitland mobilization has not been evaluated in knee OA.
Learn More >It is unclear how to address PTSD in the context of chronic pain management. Here we examine the potential benefits of an addition of prolonged exposure (PE) therapy for PTSD for adults attending multidisciplinary CBT for chronic pain.
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