Background
This study marks the first epidemiological evaluation of the prevalence and burden of chronic neuropathic pain (NeP) in an Asian population. The objective of this nationwide ...cross‐sectional study was to identify the characteristics of individuals with NeP, detect the NeP features that affect their quality of life (QOL), and demonstrate the negative effects of NeP on social and daily living as well as comorbidities including depression, anxiety and sleep disorders.
Methods
We mailed a cross‐sectional, population‐based epidemiological survey to a random nationwide sample of 10,000 Japanese adults over 20 years old.
Results
The response rate was 54.4% (2445 men, 2992 women; mean age, 53.4 years). Prevalence of chronic pain was 16.6%, and prevalence of NeP was 3.2% as detected by the PainDETECT. Participants with NeP showed significantly lower quality of life according to scores on the EuroQol‐5 Dimensions scale (p < 0.001), higher levels of psychological distress on the Kessler 6‐item psychological distress scale (p < 0.001), poorer sleep quality (p < 0.001), and more workdays lost (p < 0.001) than did participants without NeP. Linear regression modelling showed that widespread pain, thermal hyperalgesia and pressure‐induced pain had strong associations with lower QOL, with regression coefficients of −0.046 (p < 0.001), −0.038 (p < 0.001), and −0.040 (p < 0.001), respectively.
Conclusions
This study is the first to report the prevalence of NeP in an Asian population using a validated questionnaire. This study provides compelling evidence that chronic NeP is more strongly associated with poorer QOL, mental health and social well‐being than CP without a neuropathic component.
Significance
This population‐based nationwide epidemiological study revealed the prevalence, characteristics, and negative effects of chronic pain with neuropathic components in Asian society. The prevalence of neuropathic pain was 3.2% with PainDETECT.
High-speed photography is a powerful tool for studying fast dynamics in photochemistry, spintronics, phononics, fluidics and plasma physics. Currently, the pump-probe method is the gold standard for ...time-resolved imaging, but it requires repetitive measurements for image construction and therefore falls short in probing non-repetitive or difficult-to-reproduce events. Here, we present a motion-picture camera that performs single-shot burst image acquisition without the need for repetitive measurements, yet with equally short frame intervals (4.4 trillion frames per second) and high pixel resolution (450 × 450 pixels). The principle of this method--'motion picture femtophotography'--is all-optical mapping of the target's time-varying spatial profile onto a burst stream of sequentially timed photographs with spatial and temporal dispersion. To show the camera's broad utility we use it to capture plasma dynamics and lattice vibrational waves, both of which were previously difficult to observe with conventional methods in a single shot and in real time.
Summary Objective Subchondral bone plays a role in generating knee joint pain in osteoarthritis (OA). The objective of this study was to clarify nociceptive phenotype alterations of subchondral bone ...afferents of the distal femur in mono-iodoacetate (MIA)-induced OA rats. Methods OA was induced by intra-articular injection of MIA in rats. Two different retrograde tracers were separately injected into the knee joint cavity and the subchondral bone to identify joint and subchondral bone afferents. Immunohistochemistry was used at 2 weeks (early stage) and 6 weeks (advanced stage) after MIA injection to determine the expression of nociceptive markers (calcitonin gene-related peptide (CGRP) and tyrosine receptor kinase A (TrkA)) and the soma size distribution of CGRP-immunoreactive (IR) neurons. Histological subchondral bone and cartilage damage was scored according to the Osteoarthritis Research Society International grading system. Pain-related behavior was evaluated using weight distribution and mechanical sensitivity of the hind paw. Results OA caused an up-regulation of CGRP, TrkA and enlargement of soma size of CGRP-IR neurons in both joint and subchondral bone afferents. CGRP and TrkA expression in subchondral bone afferents gradually increased over 6 weeks. Furthermore, up-regulation of CGRP and TrkA in subchondral bone afferents displayed a strong correlation with the subchondral bone damage score. Conclusion Up-regulation of nociceptive markers in subchondral bone afferents correlated with subchondral bone damage, suggesting that subchondral bone is a therapeutic target, especially in the case of advanced stage knee OA. In particular, CGRP and TrkA are potentially molecular therapeutic targets to treat joint pain associated with subchondral lesions.
•Shock Index is a useful indicator to detect postpartum hemorrhage in vaginal delivery.•Shock Index peaks at 10–15 min after delivery during cesarean delivery.•Spinal anesthesia and various ...medications affect Shock Index during cesarean delivery.•Shock Index does not correlate with total blood loss.•Shock Index has poor ability to detect postpartum hemorrhage during cesarean delivery.
The Shock Index (SI), defined as heart rate divided by systolic blood pressure, is reportedly an early surrogate indicator for postpartum hemorrhage (PPH). However, most previous studies have used clinical data of women who delivered vaginally. Therefore, we aimed to evaluate the SI pattern during cesarean delivery and determine its usefulness in detecting PPH.
This was a single-center retrospective study using the clinical data of women (n = 331) who underwent cesarean delivery under spinal anesthesia at term between 2018 and 2021. We assessed the SI pattern stratified by total blood loss and evaluated the predictive performance of each vital sign in detecting PPH (total blood loss ≥1000 mL) based on the area under the receiver operating characteristic curve (AUROC).
At 10–15 min after delivery, the mean SI peaked between 0.84 and 0.90 and then decreased to a level between 0.72 and 0.77, which was similar to that upon entering the operating room. Among 331 women, 91 (27.5%) were diagnosed with PPH. There was no correlation between SI and total blood loss (rs = 0.02). The SI had low ability to detect PPH (AUROC 0.54, 95% confidence interval 0.47 to 0.61), which was similar to other vital signs (AUROCs 0.53–0.56).
We determined the pattern of SI during cesarean delivery. We found no correlation between SI and total blood loss. Unlike in vaginal delivery, the prognostic accuracy of SI for PPH detection in cesarean delivery was low.
Purpose: Neuropathic pain is sometimes difficult to manage because of limited efficacy of analgesic monotherapy even at high doses. Combination therapy may help address this issue, but there is ...little evidence for its effectiveness. Therefore, we evaluated the efficacy of combination therapy with pregabalin, an anchor drug for treating neuropathic pain, using the rat L5 spinal nerve ligation model. Methods: Experiments were performed on four-week-old L5 spinal nerve ligated male Sprague-Dawley rats. Mechanical allodynia was assessed using the von Frey test, where the 50% withdrawal threshold was evaluated for five drugs: pregabalin, duloxetine, venlafaxine, tramadol, and celecoxib. The single-drug experiment included 112 rats, where each drug was tested independently. Median effective doses (ED.sub.50s) were determined. Combinations of pregabalin with each of the other four drugs were tested (n=84). The 50% withdrawal threshold in the von Frey test was evaluated. The ED.sub.50 of each combination was determined experimentally. Isobolographic analyses were conducted to assess the synergistic potential of the drug combinations, excluding pregabalin-celecoxib, since the ED.sub.50 of celecoxib could not be determined. Results: In the single-drug experiment, all drugs except celecoxib resulted in a dose-dependent increase in the 50% withdrawal threshold 2 h after administration, with a maximum possible effect ranging from 4.4% to 79.6%. Similarly, all pregabalin combinations demonstrated a dose-dependent increase in the 50% withdrawal threshold, with pregabalin-tramadol showing the greatest increment. Isobolographic analysis of this combination revealed synergistic effects. Specifically, the combination index was y=0.4 (<1). Combinations of pregabalin with duloxetine and venlafaxine demonstrated additive (y=0.9) and antagonistic effects (y=2.0), respectively. Conclusion: This study demonstrated that combination of pregabalin with tramadol has synergistic antiallodynic effects, while that with duloxetine has additive effects. Moreover, pregabalin combined with venlafaxine was potentially antagonistic. Pregabalin combined with tramadol may serve as a promising drug combination for the effective management of neuropathic pain. Keywords: analgesic, animal model, isobologram, synergistic effects
A two-scale thermo-mechanical model for porous solids is derived and is implemented into a multi-scale multi-physics analysis method. The model is derived based on the mathematical homogenization ...method and can account for the scale effect of unit cells, which is our particular interest in this paper, on macroscopic thermal behavior and, by extension, on macroscopic deformation due to thermal expansion/contraction. The scale effect is thought to be the result of microscopic heat transfer, the amount of which depends on the micro-scale pore size of porous solids. We first formulate a two-scale model by applying the method of asymptotic expansions for homogenization and, by using a simple numerical model, verify the validity and relevancy of the proposed two-scale model by comparing it with a corresponding single-scale direct analysis with detailed numerical models.
A novel decellularization method using sonication treatment is described. Sonication treatment is the combination of physical and chemical agents. These methods will disrupt cell membrane and release ...cell contents to external environments. The cell removal was facilitated by subsequent rinsing of sodium dodecyl sulfate detergents. Sonication treatment is used in the preparation of complete decellularized bioscaffolds. The aim of this study is to confirm the usefulness of sonication treatment for preparation of biological scaffolds. In this study, samples of aortic tissues are decellularized by sonication treatment at frequency of 170 kHz in 0.1% and 2% sodium dodecyl sulfate detergents for 10-h treatment time. The relation between decellularization and sonication parameters such as dissolved oxygen concentration, conductivity, and pH is investigated. Histological analysis and biomechanical testing is performed to evaluate cell removal efficiency as well as changes in biomechanical properties. Minimal inflammation response elicit by bioscaffolds is confirmed by xenogeneic implantation and immunohistochemistry. Sonication treatment is able to produce complete decellularized tissue suggesting that these treatments could be applied widely as one of the decellularization method.
Background
The subchondral bone of the distal femur is a source of pain caused by osteoarthritis (OA) or spontaneous osteonecrosis of the knee. However, nociceptive phenotype of dorsal root ganglia ...(DRG) neurons innervating the subchondral bone in rat knee joints has not been clarified.
Methods
Retrograde labelling was used to identify afferents innervating the subchondral bone of the distal femur and the knee joint in rats. The nociceptive phenotype markers calcitonin gene‐related peptide (CGRP), tyrosine receptor kinase A (TrkA), neurofilament 200 (NF200) and isolectin B4 (IB4), segmental distribution and the soma size of backlabelled DRG neurons were examined. Furthermore, we evaluated the differences in nociceptive phenotype between the subchondral bone and the knee joint afferents.
Results
The majority (60%) of the subchondral bone afferents were localized in L3 DRGs and fewer in L4 and L5, while the knee joint afferents were localized mainly in L3 and L4. The percentage of CGRP immunoreactive (IR), TrkA‐IR, NF200‐IR and IB4‐binding neurons in the subchondral bone afferents were 50%, 65%, 35% and 0%, respectively. The percentage of CGRP‐IR and TrkA‐IR neurons in the subchondral bone afferents was significantly higher than that in the knee joint afferents, respectively (p < 0.05).
Conclusion
The majority of sensory DRG neurons innervating the subchondral bone of the distal femur were CGRP‐IR and TrkA‐IR. It is expected that therapeutic approaches targeting CGRP and TrkA could be effective in attenuating pain from the subchondral bone in knee joints.
Background
Synovial fluid in inflamed joint shows a drop in pH, which activates proton‐gated ion channels in nociceptors. No studies have ever tried to develop and characterize acid‐induced joint ...pain.
Methods
Rats were injected intra‐articularly with pH 4.0 acidic saline twice, 5 days apart. Pain‐related behaviour tests including weight‐bearing asymmetry, paw withdrawal threshold and knee compression threshold were conducted. To clarify the roles of proton‐gated ion channels, rats were injected intra‐articularly with selective antagonists for ASIC1a, ASIC3 and TRPV1 on day 5 (before the second injection) or on day 14. Underlying peripheral and central pain mechanisms were evaluated using joint histology, interleukin‐1β concentrations in the synovium, single‐fibre recording of the knee afferent and expression of phosphorylated cyclic adenosine monophosphate‐responsive element‐binding protein (p‐CREB) in the spinal dorsal horn.
Results
Repeated injections of acidic saline induced weight‐bearing asymmetry, decrease in paw withdrawal threshold and knee compression threshold bilaterally, which lasted until day 28. Early administration of ASIC3 antagonist reduced the bilateral and long‐lasting hyperalgesia. Neither articular degeneration nor synovial inflammation was observed. C‐fibre of the knee afferent was activated by acidic saline, which was attenuated by pre‐injection of ASIC3 antagonist. p‐CREB expression was transiently up‐regulated bilaterally on day 6, but not on day 14.
Conclusion
We developed and characterized a model of acid‐induced long‐lasting bilateral joint pain. Peripheral ASIC3 and spinal p‐CREB played important roles for the development of hyperalgesia. This animal model gives insights into the mechanisms of joint pain, which is helpful in developing better pain treatments.
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