Changes In Pain Behavior Research Articles

AGMATINE ADMINISTRATION ALLEVIATES NERVE DAMAGE AND IMPROVES NERVE FUNCTION IN METHOTREXATE INDUCED PERIPHERAL NEUROPATHY IN RATS

Objective: Chemotherapeutic agents can produce neurodegenerative changes. This study was conducted to assess the therapeutic potential of agmatine, a neuromodulator, on methotrexate induced neurodegeneration in sciatic nerve. Materials and Methods: 40 male Wistar albino rats were assigned into four groups at random as control, methotrexate, agmatine and methotrexate-agmatine. Methotrexate was injected intraperitoneally at a 37.5 mg/kg/week dose for 3 weeks. Afterwards, agmatine was administered intraperitoneally twice a day at a 40 mg/kg dose for 7 days. Sciatic functional index, nociceptive pain perception and behavioral changes were analyzed every week. Nerve conduction velocity was evaluated. Apoptotic activity and mitophagy, histopathological changes in sciatic nerves were examined. Results: Methotrexate administration resulted in a prolonged escape time to the platform and decreased the time spent in the quadrant in the water maze test; elevated nociceptive latencies; decreased the number of frames passed in the open field test; reduced sciatic NCV and SFI score. Besides, methotrexate administration caused a reduction in myelin thickness and axon diameter in sciatic nerve and a more intense glial fibrillary acidic protein immunoreactivity. Methotrexate administration triggered an increase in the Bax/Bcl-2 protein expression ratio without changing the expression level of Parkin, indicating a slight apoptotic activation. agmatine administration improved methotrexate induced changes in behavioral performances, nociceptive pain perception, nerve conduction, SFI scores and histopathological changes. Conclusion: Agmatine has been demonstrated to possess a therapeutic potential in methotrexate induced degeneration and peripheral neuropathy in the rat sciatic nerve.

Changes in SLITRK1 Level in the Amygdala Mediate Chronic Neuropathic Pain-Induced Anxio-Depressive Behaviors in Mice.

Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1) protein is important for synaptic remodeling and is highly expressed in the amygdala, an important brain region involved in various emotional behaviors. We examined whether SLITRK1 protein in the amygdala participates in NPP and comorbid ADD. A chronic NPP mouse model was constructed by L5 spinal nerve ligation; changes in chronic pain and ADD-like behaviors were measured in behavioral tests. Changes in SLITRK1 protein and excitatory synaptic functional proteins in the amygdala were measured by immunofluorescence and Western blot. Adeno-associated virus was transfected into excitatory synaptic neurons in the amygdala to up-regulate the expression of SLITRK1. Chronic NPP-related ADD-like behavior was successfully produced in mice by L5 ligation. We found that chronic NPP and related ADD decreased amygdalar expression of SLITRK1 and proteins important for excitatory synaptic function, including Homer1, postsynaptic density protein 95 (PSD95), and synaptophysin. Virally-mediated SLITRK1 overexpression in the amygdala produced a significant easing of chronic NPP and ADD, and restored the expression levels of Homer1, PSD95, and synaptophysin. Our findings indicated that SLITRK1 in the amygdala plays an important role in chronic pain and related ADD, and may prove to be a potential therapeutic target for chronic NPP-ADD comorbidity.

Психологические реакции детей на ситуацию хирургического лечения: обзор исследований

<p>The article presents a review of studies on the psychological reactions of children to a situation of surgical treatment. Surgical treatment is considered as a situation with a high potential for stress, which is due to the variety and high intensity of stress effects which are experienced by the child as new and uncontrolled. Negative psychological responses are observed in children both at the preoperative and postoperative stages. At the preoperative stage, preoperative anxiety is highly prevalent. The risk of its development depends on a complex of factors related to the child themself, his/her environment, as well as the disease, hospital environment, the treatment and the circumstances of hospitalization. Preoperative anxiety is a risk factor for more severe pain symptoms, emotional and behavioral changes in the postoperative period. The article discusses the modern methods for the prevention and correction of preoperative anxiety and postoperative emotional and behavioral changes in children: the presence of parents during the induction of anesthesia, providing information using modern technologies and principles of social learning, distraction and other cognitive and behavioral methods for the correction of the mental state, multimodal methods for harmonizing the emotional state and behavior of children (art therapy, play therapy, clown therapy). The authors come to the conclusion that further research is needed in order to develop algorithms for the psychological support of children in a situation of surgical treatment, taking into account their age, clinical characteristics, the psychological features of the child and his/her parents.</p>

Exploring gene signatures and regulatory networks in a rat model of sciatica: implications and validation in neuropathic pain.

Sciatica (neuropathic pain [NP]) is a common disease characterized by pain from radiation along the sciatic nerve. The aim of this study was to study the genes associated with chronic systolic injury of sciatic nerve (SCN-CCI) in rats by RNA-Seq technique, and to explore their potential as therapeutic targets. Sciatic nerve rat model was obtained by ligation of sciatic nerve and divided into two groups: SCN-CCI group and Sham group. Behavioral assessments were performed to evaluate pain sensitivity, following which their spinal cord dorsal horn were resected and RNA sequencing was conducted to identify differentially expressed genes (DEGs). Bioinformatics and functional enrichment analysis was performed to identify promising DEGs and their related biological processes and pathways associated with SCN-CCI. PPI network analysis and hub gene identification were conducted. QRT-PCR, western blot, ELISA, and immunofluorescence staining were performed on rat models to validate the expression of these hub genes and investigate related proteins and inflammatory markers. The SCN-CCI rat model was successfully obtained, exhibiting increased pain sensitivity compared to the Sham group, as indicated by decreased mechanical allodynia thresholds, thermal latencies, and increased paw withdrawals. RNA-Seq analysis identified 117 DEGs in the SCN-CCI rat model, involved in various biological processes and pathways related to sciatica. PPI network analysis revealed hub genes, including Ly6g6e, which exhibited significant differential expression. QRT-PCR and Western blot analysis confirmed the expression patterns of these hub genes. Pain behavior assessment demonstrated reduced pain thresholds and increased paw flinching responses in the SCN-CCI group. Furthermore, the SCN-CCI group showed upregulated expression of Ly6g6e, increased protein levels of Ly6g6e, CGRP, and NGF, as well as elevated levels of IL-1β, MCP-1, and IL-6, and microglial cell activation in the spinal dorsal horn. ELISA results confirmed the increased levels of IL-1β, MCP-1, and IL-6 in the spinal dorsal horn. These comprehensive findings provide valuable insights into the SCN-CCI rat model, DEGs associated with sciatica, hub genes (Ly6g6e as promising targets), pain behavior changes and molecular alterations.

The effects of the cholinergic system on carrageenan-induced arthritis

The cholinergic system has been found to make an anti-inflammatory effect through the cholinergic anti-inflammatory pathway (CAIP), which suppresses the production of pro-inflammatory cytokines by secreting acetylcholine, a major neurotransmitter. However, no studies have been conducted on the effects of CAIP on joint pain and inflammation. In this study, we investigated the effects of muscarinic acetylcholine receptors (mAChRs) in knee arthritis. To examine pain behavioral changes, atropine (or saline for sham control) was pretreated in the joint cavity of rats at 1 % carrageenan + 5, 10, and 30 μL and the dynamic weight-bearing evaluation was performed. Synovial membranes were collected and cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) were measured using a western blot. Hematoxylin and eosin staining was performed. Compared to that of the sham group, the weight-bearing of the affected knee joint significantly increased in the 1 % carrageenan + 10 μL atropine group (p < 0.05). However, no significant changes were observed in the 1 % carrageenan + 5 and 30 μL atropine groups. COX-2 and IL-1β and the number of inflammatory cells in synovial membrane significantly increased with 1 % carrageenan + 10 μL of atropine (p < 0.05). These results suggest that cholinergic system is involved in knee joint pain and inflammation and that mAChRs are potential therapeutic targets for knee joint arthritis.

Menstrual Problems: Menorrhagia and Primary Dysmenorrhagia

Menstrual problems can considerably affect a girl’s status in life, accompanied by two universal issues: menorrhagia and basic dysmenorrhea. Menorrhagia, characterized by difficult menstrual draining, is a condition in which a woman experiences extended periods or excessive blood flow. This condition may incapacitate you, leading to blood deficiency, fatigue, and public restraints. The underlying causes of menorrhagia can change, including hormonal imbalances, uterine Fibroids, or added medical environments, which typically include a particularized record of what happened and a physical examination attended by potential situations such as cure, hormonal therapy, or surgical attack. Primary dysmenorrhea, in another way, refers to harsh menstrual cramps without some fundamental healing condition. It is a common issue among daughters and usually occurs during the first few days of the period. The exact cause of basic dysmenorrhea is not well understood; however, it is expected to be associated with prostaglandin production and uterine shortening. Women with primary dysmenorrhea grant permission for sharp, incapacitating pain, nausea, and additional discomfort, which upset their regular lives. Management options include pain relievers, hormonal contraceptives, behavioral changes, and heat therapy.

Neurotropin Alleviates Bortezomib-Induced Neurotoxicity Via Microglial Neuroinflammation

Objective: To investigate the effect of neurotropin (NTP) on the prevention and amelioration of neurotoxicity induced by bortezomib (BTZ)-based chemotherapy regimens and the possible mechanism of action, and to provide new ideas for the prevention mechanism and treatment of bortezomib-induced peripheral neuropathy (BIPN). Methods: The BIPN model was constructed by injecting bortezomib （ BTZ group ）or bortezomib+saline ( BTZ+NS group)into the tail vein of C57BL/6 mice. After successful modeling, NTP was added to take intraperitoneal injections for 4 weeks, which were defined to be NTP group. In order to assess the severity of BIPN, systemic toxicity, pain behavioral and sensorimotor kinetic changes in mice of different group were observed while transmission electron microscopy examination was used to observe the damage of peripheral nerve ultrastructure and myelin thickness. Immunofluorescence staining method was used to detected the activation of spinal cord microglial and their expression level of inflammatory factors such as IL-1β, IL-6 and TNF-α. ELISA was used to detected the expression of IL-1β, IL-6 and TNF-α in the dorsal horn homogenate of the spinal cord; Western blot to detect the protein expression of pathway-associated proteins JAK/STAT. Results: The Compared with the Control group, the BTZ and BTZ+NS groups showed significant decreases in mechanical, thermal pain thresholds and motor coordination compared with the Control group (P&amp;lt;0.05), and ultrastructural damage to the peripheral nerves, with demyelinating lesions and a significant reduction in the overall thickness of myelin sheaths in myelinated fibers (0.62±0.08 Vs 0.56±0.12, P＜0.01). NTP administration significantly improved pain behavioral changes, reduced ultrastructural damage, reversed demyelinating lesions and significantly increased myelin thickness (0.56±0.06 Vs 0.62±0.08, P＜0.01) in model mice compared with BTZ group. Immunofluorescence staining suggested that microglia in the dorsal horn of the spinal cord of mice in the BTZ group and the BTZ+NS group were significantly activated, which were shown the fluorescence ratio of IBA-1 + was significantly increased (2.55±0.61 Vs 0.55±0.04，2.42±0.89 Vs 0.55±0.04，P＜0.0001), while NTP significantly improved the activation of microglia in the model mice (0.71±0.13 Vs 2.55±0.61, 0.71±0.13 Vs 2.42±0.89, P&amp;lt;0.0001). The co-staining results suggest that the increase in inflammatory factors may originate from microglia. ELISA results that the expression level of IL-6 and TNF-α in NTP administration group significantly decreased compared with the group of BTZ group (IL-6: 37.87±23.2 Vs 111.8±6.0, P＜0.05; TNF-α: 547.9±17.11 Vs 998.8±333.4, P＜0.05) and the BTZ+NS group (IL-6: 37.87±23.2 Vs 88.3±15.58, P&amp;lt;0.05; TNF-α: 547.9±17.11 Vs 768.3±37.45, P&amp;lt;0.05) in the dorsal horn homogenate of the spinal cord. The results of spinal cord proteomics showed that neurotropin could induce the changes of differential proteins, such as PI3K-AKT, MAPK, JAK/STAT, which were related to inflammation. Moreover, these differential proteins can be significantly enriched in the JAK/STAT KEGG Pathway. The KEGG pathway of differential protein enrichment in the spinal cord of differential BIPN mice was detected by proteomics chip after NTP treatment, and the JAK/STAT pathway was significantly down-regulated after NTP treatment. Western blot showed that the protein expression of JAK1/STAT3 decreased after NTP administration. Conclusion: Neurotropin alleviates bortezomib induced neurotoxicity through microglial neuroinflammation, and may reduce the release of glial inflammation by regulating JAK1/STAT3 signaling pathway, thus playing a therapeutic role in BIPN. Repeated experiments are needed for further research. Keywords: Neurotropin, Bortezomib, Peripheral neuropathy, Neuroinflammation

Changes in ion-channels in the dorsal root ganglion after exposure to autologous nucleus pulposus and TNF. A rat experimental study

PurposeIt is known that contact of nucleus pulposus with the dorsal root ganglion may induce changes in nerve conduction and pain behavior. It has also been suggested that the behavioristic changes are caused by changes in voltage-gated ion channels, which in turn have been upregulated by TNF. Such upregulations have previously been shown for NaV 1.8 and NaV 1.9. In this investigation, we expanded the number of studied ion channels after the application of nucleus pulposus or TNF. MethodsFollowing removal of the left L4-5 fact joint, a disc puncture was performed and the dorsal root ganglion was exposed to nucleus pulposus (n = 5) and TNF (n = 5). Operated rats without disc puncture served as sham (n = 5) and 5 non-operated (naïve) rats were included. After 24 h, the DRGs were harvested and analyzed by quantitative PCR on validated pre-spotted primer plates displaying genes for 90 voltage-gated ion channels. ResultsIt was evident that the changes in operated animals were separate from the naïve rats. It was also apparent that gene expression changes in rats with nucleus pulposus or TNF application showed similar trends and were also separated from sham-operated animals. ConclusionThe application of nucleus pulposus and TNF onto the DRG in rats induces comparable changes in gene expression of several ion channels. Since the changes induced by TNF and NP are similar, one might also suspect that TNF mediates the NP-induced changes. However, such a mechanism needs further investigation.

Opioid tapering after surgery and its association with patient-reported outcomes and behavioral changes: a mixed-methods analysis

IntroductionOpioid tapering after surgery is recommended among patients with chronic opioid use, but it is unclear how this process affects their quality of life. The objective of this study was...

Development and Evaluation of a Rat Model of Full-Thickness Cartilage Defects.

Cartilage defects of the knee joint caused by trauma are a common sports joint injury in the clinic, and these defects result in joint pain, impaired movement, and eventually, knee osteoarthritis (kOA). However, there is little effective treatment for cartilage defects or even kOA. Animal models are important for developing therapeutic drugs, but the existing models for cartilage defects are unsatisfactory. This work established a full-thickness cartilage defects (FTCD) model by drilling holes in the femoral trochlear groove of rats, and the subsequent pain behavior and histopathological changes were used as readout experiments. After surgery, the mechanical withdrawal threshold was decreased, chondrocytes at the injured site were lost, matrix metalloproteinase MMP13 expression was increased, and type II collagen expression decreased, consistent with the pathological changes observed in human cartilage defects. This methodology is easy and simple to perform and enables gross observation immediately after the injury. Furthermore, this model can successfully mimic clinical cartilage defects, thus providing a platform for studying the pathological process of cartilage defects and developing corresponding therapeutic drugs.

Telehealth Group-Based Pain Management Programs Using the Therapeutic Alliance and Group Dynamics as Key Predictor Variables

Telehealth pain management has become instrumental in managing patients with chronic pain (CP) since the onset of the COVID-19 pandemic. The primary aim of this study was to investigate whether various covert therapeutic variables aid in the efficacy of telehealth group-based pain management programs (GPMPs). The therapeutic alliance (TA), group dynamics (GDs), attendance and change in pain neuroscience knowledge were evaluated as potential predictor covert variables of change in pain outcome measures and readiness to change (RTC) maladaptive pain behaviors. Telehealth GPMP groups met once a week for 3 hours via zoom software and ran over a course of 6 weeks in which CP self-management techniques were taught. Pain outcome measures were taken at baseline and after the final telehealth GPMP. In addition, the measures around pain neuroscience understanding were examined at baseline and post-intervention. Finally, the TA and GDs were examined at post-treatment using the Therapeutic Group Context Questionnaire (TGCQ). Various statistical procedures were utilized to determine the predictive nature between the specific variables. The TA and GDs showed statistically significant ( p < 0.05) predictive relationships with improved changes in maladaptive pain behaviors and pain self-efficacy. There was also a statistically significant ( p < 0.05) predictive relationship between maladaptive pain behavioral changes and improvements in pain self-efficacy, pain catastrophizing and pain kinesiophobia. This research suggested that covert components in a telehealth GPMP such as changes in readiness to change (RTC) maladaptive pain behaviors, the TA, and GDs are all strong predictors of improvements in pain outcome measures following such an intervention.

Insular cortex stimulation alleviates neuropathic pain via ERK phosphorylation in neurons.

The clinical use of brain stimulation is attractive for patients who have side effects or tolerance. However, studies on insular cortex (IC) stimulation are lacking in neuropathic pain. The present study aimed to investigate the effects of IC stimulation (ICS) on neuropathic pain and to determine how ICS modulates pain. Changes in pain behaviors were observed following ICS with various parameters in neuropathic rats. Western blotting was performed to assess molecular changes in the expression levels of phosphorylated extracellular signal-regulated kinase (pERK), neurons, astrocytes, and microglia between experimental groups. Immunohistochemistry was performed to investigate the colocalization of pERK with different cell types. The most effective pain-relieving effect was induced at 50 Hz-120 μA in single trial of ICS and it maintained 4 days longer after the termination of repetitive ICS. The expression levels of pERK, astrocytes, and microglia were increased in neuropathic rats. However, after ICS, the expression levels of pERK were decreased, and colocalization of pERK and neurons was reduced in layers 2-3 of the IC. These results indicated that ICS attenuated neuropathic pain by the regulation of pERK in neurons located in layers 2-3 of the IC. This preclinical study may enhance the potential use of ICS and identify the therapeutic mechanisms of ICS in neuropathic pain.

Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats.

Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs.

Penerapan Teknologi Virtual Reality terhadap Perilaku Nyeri Pasien Pasca Bedah ORIF Fraktur Ekstremitas Bawah Saat Penggantian Balutan Luka

This study aims to identify the effect of applying virtual reality technology on pain behavior in postoperative ORIF patients with lower extremity fractures during dressing changes. The type of research used is a quasi-experimental nonequivalent control group pretest-posttest design. The sample in this study amounted to 50 patients after ORIF surgery for lower extremity fractures who underwent a wound dressing replacement procedure with a consecutive sampling technique. The research instrument consisted of a demographic data questionnaire, virtual reality devices and media and the Behavioral Pain Scale-Non Intubated (BPS-NI). The results showed that as many as 22 respondents (88%) who received virtual reality intervention when changing wound dressings did not show any pain, while the other 3 respondents experienced mild pain (12%). The results of the statistical test analysis Wilcoxon-Signed Ranked and Mann Whitney obtained a p-value &lt;0.05. In conclusion, there is an effect of applying virtual reality technology in reducing pain as indicated by changes in pain behavior of patients after ORIF surgery for lower extremity fractures when changing wound dressings.&#x0D; Keywords: Change of Wound Bandage, Pain Behavior, Virtual Reality

Exercise reduces pain behavior and pathological changes in dorsal root ganglia induced by systemic inflammation in mice

Emerging research indicates that physical activity can ameliorate chronic pain, but the underlying mechanisms are still largely obscure. In particular, little is known on the mechanisms behind exercise-induced analgesia in the setting of inflammatory pain. In our previous studies on systemic inflammation in mice using lipopolysaccharide (LPS) administration, we characterized satellite glial cells (SGCs) and neurons in dorsal root ganglia (DRG). We found that a week post-LPS injection, the sensitivity to mechanical stimulation was lowered, SGCs were activated and coupling among SGCs increased 3 to 4.5-fold. In the present work, we examined the effects of exercise (free wheel running) on tactile sensitivity and on pathological changes in mouse DRG in the LPS model. We found that exercise prevented tactile hypersensitivity, and also reversed the cellular changes in the DRG induced by LPS that were listed above. We propose that the analgesic effect of exercise is at least partly mediated by reversing the pathological changes in SGCs.

The Contribution of TSLP Activation to Hyperalgesia in Dorsal Root Ganglia Neurons of a Rat.

Peripheral nerve injury involves divergent alterations within dorsal root ganglia (DRG) neurons sensitized by persistent inflammation. Thymic stromal lymphopoietin (TSLP) production is crucial in the development of chronic inflammatory responses. Herein, we investigate the changes of TSLP expression in rats’ DRG neurons between injured and uninjured sides in the same rat. Linalyl acetate (LA) was served as a TSLP inhibitor and given intraperitoneally. Rats were assigned to be group of chronic constriction injury (CCI) of the sciatic nerve and the group of CCI of the sciatic nerve administrated with LA. Over 14 days, the rats were measured for paw withdrawal thresholds. DRGs were collected to assess morphological changes via immunofluorescence study. After receiving CCI, the rats rapidly developed mechanical hyperalgesia. TSLP expression at DRG, on the ipsilateral injured side, was consistent with changes in pain behaviors. TSLP appeared in nerve fibers with both small diameters and large diameters. Additionally, TSLP was expressed mostly in transient receptor potential vanilloid-1 (TRPV1)-positive nociceptive neurons. Administration with LA can attenuate the pain behaviors and expression of TSLP in DRG neurons, and in apoptotic neurons at the injured side, but not in the contra-lateral uninjured side. Overall, these results imply that altered expressions of TSLP in nociceptive DRG neurons contributed to mechanical hyperalgesia in a CCI rat model.

Detection and clinical impact of anxiety in Children undergoing general anesthesia compared to the standard of care of a pediatric hospital.: Detección e impacto clínico de la ansiedad en niños sometidos a anestesia general en comparación con el estándar de atención de un hospital pediátrico.

Introduction: The impact of preoperative anxiety causes significantly postoperative pain, delirium, sleep disturbances, and other maladaptive behavioral changes that last for weeks or months after surgery. Method and results: We performed an observational, cross-sectional, descriptive study in 97 children aged 7 to 10 years who underwent elective surgery. The manifest anxiety scale in children (CMA-R) were applied to them, frequencies, percentages and cross-tests were used to find factors associated with anxiety. The results are significantly compared with the literature, presenting anxiety in 52.5% of the patients, where the socioeconomic level influences that this occurs. Conclusions: The study results demonstrate that the scale is helpful and attractive in detecting preoperative anxiety in children undergoing outpatient surgery compared to the standard care protocol in pediatric hospitals.

Особливості відновлення м’язів за умов експериментальної післятравматичної контрактури

The frequency of traumatic injuries of the maxillofacial area and the degree of their severity, have been increasing in recent years. The introduction of modern methods of treatment made it possible to improve the results of treatment and shorten its duration. Myogenic contractures develop as a complication after facial injuries, soft tissue injuries, in particular, masticatory muscles. The gastrocnemius muscle of a rat has the same striated structure as the pterygoideus medialis muscle of a person. The purpose of the work is to study the regeneration of striatal muscles with post-traumatic contractures on the basis of combined treatment of laboratory rats. Materials and methods. The study was carried out on 45 sexually mature 12 months old outbred white male rats, which weighed 180-200 g. In animals, reflex post-traumatic muscle contractures (traumatic myositis) resulting from the slaughter of calf muscles (without violating the integrity of muscle tissue) were simulated on the posterior left leg. The rats were divided into two groups. Group 1 included 21 animals that did not receive treatment and whose wounds healed by secondary intention. Group 2 included 24 rats that received combined treatment: on the 2nd day after surgery – general (oral) administration of the drug with the active substance cyclobenzaprine hydrochloride – 0.15 mg, once a day with daily procedures of magnetic laser therapy on the affected hind limb. Results and discussion. Depending on the signs of pain behavior (changes in behavior, restriction of movement, increased sensitivity, pain), the intensity of myogenic pain syndrome was assessed (low, moderate, high, very high). It was found that the use of combined treatment (magnetic laser therapy and the use of cyclobenzaprine hydrochloride) led to the normalization of behavioral and motor reactions by the 28th day: 56% of rats didn’t feel any pain and 44% had a low level of pain. The animals with the same trauma, which weren’t treated, showed a high and moderate level of pain. On the 28th day these animals could lean on their hind limbs while they were moving. However, they could not fully move due to a sharp restriction of their left hind limb function. The obtained results are the basis for the development of new approaches to improving the methods of prevention and rehabilitation treatment of contractures using magnetic laser therapy and central muscle relaxants. Conclusion. It was found that the use of magnetic laser therapy and cyclobenzaprine hydrochloride inhibited the development of an acute inflammatory reaction in the damaged muscle tissue of the hind limb of animals, accelerated and optimized reparative processes, which prevented excessive, functionally significant growth of connective tissue

Optimizing Pediatric Induction Experiences Using Human-centered Design

PurposeAnesthesia inhalation induction (falling asleep for a surgery using a medical mask) is often stressful for children. When children become anxious about induction, they may resist wearing the anesthesia mask. High anxiety during induction is associated with poorer outcomes after surgery, such as increased emergence delirium, increased pain and negative behavioral changes after discharge. The purpose of this project was to design an optimal anesthesia induction experience for children, with a focus on decreasing patient anxiety during inhalation induction. DesignDesigning for the perioperative environment requires in-depth knowledge of existing processes, needs of key stakeholders, strengths/shortcomings of existing approaches, and iterative testing of design concepts. We used a human centered design model (design research) to approach this challenge. MethodsHospital staff partnered with a design team at the Live Well Collaborative. Families and staff were consulted during all phases of the design process. The iterative design research process (research, ideation, refinement) was used to develop product and process concepts for optimizing the induction experience. Requirements for an optimal induction experience were defined during the research phase through reviewing the scientific literature, process mapping and benchmarking with other products. Product and process concepts were developed during the ideation phase. Concepts were tested and refined during the refinement phase. FindingsThe research phase provided insights about the current anesthesia induction process and what interventions help engage children in medical care. Key insights included normalizing the anesthesia mask through medical play, providing patients with an increased sense of control preoperatively and during induction, and engaging multiple senses during the process. The ideation phase led to the development of several design concepts, including an app that is activated by breathing into the anesthesia mask. During the refinement phase, concepts were shared and refined with input from families and clinical staff. This phase led to the development of a novel zoo-themed gaming app. ConclusionsThe design research process facilitated the creation of a new anxiety reduction tool for the perioperative environment. The breath-controlled induction app simultaneously employs multiple evidence-based anxiety reduction techniques and is designed to seamlessly integrate into the fast-paced perioperative workflow during key stress points. Testing in the clinical setting is needed to determine the effectiveness of the app for preoperative anxiety reduction.

Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-κB pathway.

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathway-associated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathway-related proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.