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Virtual Reality Animal Rescue World: Pediatric virtual reality analgesia during just noticeable pressure pain in children aged 2-10 years old (crossover design).

Excessive pain during medical procedures is a worldwide medical problem. Most scald burns occur in children under 6, who are often undermedicated. Adjunctive Virtual Reality (VR) distraction has been shown to reduce pain in children aged 6-17, but little is known about VR analgesia in young children. This study tests whether desktop VR (VR Animal Rescue World) can reduce the just noticeable pressure pain of children aged 2-10.

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Distribution of acid-sensing ion channel subunits in human sensory neurons contrasts with that in rodents.

Acid-sensing ion channels (ASICs) play a critical role in nociception in human sensory neurons. Four genes ( and ) encoding multiple subunits through alternative splicing have been identified in humans. Real time-PCR experiments showed strong expression of three subunits , , and in human dorsal root ganglia; however, their detailed expression pattern in different neuronal populations has not been investigated yet. In the current study, using an hybridization approach (RNAscope), we examined the presence of , , and mRNA in three subpopulations of human dorsal root ganglia neurons. Our results revealed that and were present in the vast majority of dorsal root ganglia neurons, while was only expressed in less than half of dorsal root ganglia neurons. The distribution pattern of the three subunits was the same across the three populations of dorsal root ganglia neurons examined, including neurons expressing the REarranged during Transfection (RET) receptor tyrosine kinase, calcitonin gene-related peptide, and a subpopulation of nociceptors expressing Transient Receptor Potential Cation Channel Subfamily V Member 1. These results strongly contrast the expression pattern of in mice since our previous study demonstrated differential distribution of among the various subpopulation of dorsal root ganglia neurons. Given the distinct acid-sensitivity and activity dynamics among different ASIC channels, the expression differences between human and rodents should be taken under consideration when evaluating the translational potential and efficiency of drugs targeting ASICs in rodent studies.

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Research Hotspots and Trends on Acupuncture for Neuropathic Pain: A Bibliometric Analysis from 2002 to 2021.

In this study, we aimed to systematically determine the trend, research hotspots, and directions of the future development of acupuncture for neuropathic pain (NP) by bibliometric analysis.

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Spinal Cord Stimulation in Special Populations: Best Practices from the American Society of Pain and Neuroscience to Improve Safety and Efficacy.

Chronic bleeding disorders, allergy to implants, and chronic infections are all complicating factors when considering neuromodulation therapies. The American Society of Pain and Neuroscience (ASPN) determined a need for clinical guidance in these special patient populations that have increased risk of complications, in order to ensure patient safety and optimal outcomes with device implantation. The purpose of this publication was to review the published literature and explore the unique clinical challenges encountered among several special patient populations with relation to spinal cord stimulation. The executive board of the ASPN appointed a diverse group of well-established physicians to develop best practice guidelines regarding spinal cord stimulation implantation in these special populations. The physicians used the United States Preventive Services Task Force (USPSTF) structured guidelines for grading and level of certainty to make evidence-based recommendations about clinical practice. Where sufficient evidence was lacking to justify a USPSTF ranking, the physicians queried experts in neuromodulation and achieved consensus. These best practices and interventional guideline found the evidence for the use of neuromodulation in specialized patient populations to be relatively modest.

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Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats-A systematic review.

Several studies suggested an informative value of behavioral and grimace scale parameters for the detection of pain. However, the robustness and reliability of the parameters as well as the current extent of implementation are still largely unknown. In this study, we aimed to systematically analyze the current evidence-base of grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats. The following platforms were searched for relevant articles: PubMed, Embase Ovid, and Web of Science. Only full peer-reviewed studies that describe the grimace scale, burrowing, and/or nest building as pain parameters in the post-surgical phase in mice and/or rats were included. Information about the study design, animal characteristics, intervention characteristics, and outcome measures was extracted from identified publications. In total, 74 papers were included in this review. The majority of studies have been conducted in young adult C57BL/6J mice and Sprague Dawley and Wistar rats. While there is an apparent lack of information about young animals, some studies that analyzed the grimace scale in aged rats were identified. The majority of studies focused on laparotomy-associated pain. Only limited information is available about other types of surgical interventions. While an impact of surgery and an influence of analgesia were rather consistently reported in studies focusing on grimace scales, the number of studies that assessed respective effects was rather low for nest building and burrowing. Moreover, controversial findings were evident for the impact of analgesics on post-surgical nest building activity. Regarding analgesia, a monotherapeutic approach was identified in the vast majority of studies with non-steroidal anti-inflammatory (NSAID) drugs and opioids being most commonly used. In conclusion, most evidence exists for grimace scales, which were more frequently used to assess post-surgical pain in rodents than the other behavioral parameters. However, our findings also point to relevant knowledge gaps concerning the post-surgical application in different strains, age levels, and following different surgical procedures. Future efforts are also necessary to directly compare the sensitivity and robustness of different readout parameters applied for the assessment of nest building and burrowing activities.

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Analgesic Medication in Fibromyalgia Patients: A Cross-Sectional Study.

There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was "on demand" (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.

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Feasibility study of a LED light irradiation device for the treatment of chronic neck with shoulder muscle pain/stiffness.

Neck with shoulder muscle stiffness/pain is a common disorder. Commonly used physical therapy, pharmacotherapy, acupuncture, and moxibustion only temporarily alleviate the disorder in most cases, thus the disorder often recurs. Low power laser therapy is often used for neck and shoulder stiffness/pain and has been effective in clinical trials. In this study, we evaluated the safety and effectiveness of a newly developed self-care device for disorders including neck with shoulder muscle stiffness/pain. The device incorporates light-emitting diodes (LEDs), which are safer than lasers, as its light source. Ten adults with neck with shoulder muscle stiffness/pain were subject to LED irradiation (wavelength 780 nm ± 15 nm, output 750 mW, power density 3.8 W/cm2, energy density 5.7×102 J/cm2) for 3 minutes on the affected shoulder at a standard acupuncture point (GB21, Jianjing). Immediately after irradiation, the subjective symptoms of the neck with shoulder muscle stiffness and pain evaluated by a visual analog scale were improved from 58.3 mm ± 18.7 mm to 45.5 mm ± 21.5 mm and from 45.8 mm ± 23.3 mm to 39.4 mm ± 21.8 mm, respectively. The symptoms further improved after 15 minutes of irradiation. The skin temperature at the irradiated point increased from 34.3°C ± 1.1°C to 41.0°C ± 0.7°C. The increase in skin temperature was observed within approximately 5 cm of the irradiated area. There was no effect on the heart rate variability, a measure of the autonomic nervous system; however, the baroreflex sensitivity was slightly increased. No irradiation-related adverse skin events were observed. Our LED irradiation device was found to be safe, and it improved the subjective symptoms of muscle stiff neck with shoulders.

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Rheumatoid arthritis and mitochondrial homeostasis: The crossroads of metabolism and immunity.

Rheumatoid arthritis is an autoimmune disease characterized by chronic symmetric synovial inflammation and erosive bone destruction. Mitochondria are the main site of cellular energy supply and play a key role in the process of energy metabolism. They possess certain self-regulatory and repair capabilities. Mitochondria maintain relative stability in number, morphology, and spatial structure through biological processes, such as biogenesis, fission, fusion, and autophagy, which are collectively called mitochondrial homeostasis. An imbalance in the mitochondrial homeostatic environment will affect immune cell energy metabolism, synovial cell proliferation, apoptosis, and inflammatory signaling. These biological processes are involved in the onset and development of rheumatoid arthritis. In this review, we found that in rheumatoid arthritis, abnormal mitochondrial homeostasis can mediate various immune cell metabolic disorders, and the reprogramming of immune cell metabolism is closely related to their inflammatory activation. In turn, mitochondrial damage and homeostatic imbalance can lead to mtDNA leakage and increased mtROS production. mtDNA and mtROS are active substances mediating multiple inflammatory pathways. Several rheumatoid arthritis therapeutic agents regulate mitochondrial homeostasis and repair mitochondrial damage. Therefore, modulation of mitochondrial homeostasis would be one of the most attractive targets for the treatment of rheumatoid arthritis.

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Prescription quantity and duration predict progression from acute to chronic opioid use in opioid-naïve Medicaid patients.

Opiates used for acute pain are an established risk factor for chronic opioid use (COU). Patient characteristics contribute to progression from acute opioid use to COU, but most are not clinically modifiable. To develop and validate machine-learning algorithms that use claims data to predict progression from acute to COU in the Medicaid population, Adult opioid naïve Medicaid patients from 6 anonymized states who received an opioid prescription between 2015 and 2019 were included. Five machine learning (ML) Models were developed, and model performance assessed by area under the receiver operating characteristic curve (auROC), precision and recall. In the study, 29.9% (53820/180000) of patients transitioned from acute opioid use to COU. Initial opioid prescriptions in COU patients had increased morphine milligram equivalents (MME) (33.2 vs. 23.2), tablets per prescription (45.6 vs. 36.54), longer prescriptions (26.63 vs 24.69 days), and higher proportions of tramadol (16.06% vs. 13.44%) and long acting oxycodone (0.24% vs 0.04%) compared to non- COU patients. The top performing model was XGBoost that achieved average precision of 0.87 and auROC of 0.63 in testing and 0.55 and 0.69 in validation, respectively. Top-ranking prescription-related features in the model included quantity of tablets per prescription, prescription length, and emergency department claims. In this study, the Medicaid population, opioid prescriptions with increased tablet quantity and days supply predict increased risk of progression from acute to COU in opioid-naïve patients. Future research should evaluate the effects of modifying these risk factors on COU incidence.

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The history of pain measurement in humans and animals.

Pain needs to be measured in order to be studied and managed. Pain measurement strategies in both humans and non-human animals have varied widely over the years and continue to evolve. This review describes the historical development of human and animal algesiometry.

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