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Natural products for migraine: Data-mining analyses of Chinese Medicine classical literature.

Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap. We conducted a comprehensive search in the (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised. Among 614 eligible citations, the most frequently used formula was (CXCTS), and the most frequently used herb was . Dietary medicinal herbs including , , , and were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of , , , and . Symptoms of vomiting and nausea were specifically related to herbs of and . The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including , , , , , and can be further explored as nutraceuticals for migraine.

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Predictive Value of Pain Sensitization Associated with Response to Exercise Therapy in Patients with Knee Osteoarthritis: A Prospective Cohort Study.

Knee osteoarthritis (KOA) is a degenerative disease with inflammation, becoming persistent as it progresses, resulting in reduced quality of life. Exercise is the recommended treatment for KOA; however, the extent of pain reduction with exercise is heterogeneous and the prognostic implications of baseline factors in patients undergoing exercise are still unknown. This study examined the association between the response to exercise therapy and clinical outcomes, radiologic severity, and pain sensitization, and investigated the optimal predictive value for the effectiveness of exercise.

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Psychopathological and neuropsychological disorders associated with chronic primary visceral pain: Systematic review.

The World Health Organization (WHO), in its last review of its International Classification of Diseases, established a new classification for chronic pain. Among the principal categories, of particular interest is chronic primary pain as a new type of diagnosis in those cases in which the etiology of the disease is not clear, being termed as chronic primary visceral pain when it is situated in the thorax, abdomen, or pelvis. Due to the novelty of the term, the objective of the systematic review was to examine the psychopathological and neuropsychological disorders associated with chronic primary visceral pain. We carried out a search of the scientific literature following the PRISMA directives using the Pubmed, Medline, PsycInfo and Scopus databases. A total of 33 articles were selected after applying the inclusion and exclusion criteria. The analysis of the studies showed that most persons with chronic primary visceral pain suffer from at least one psychological disorder; the most prevalent being anxiety, depressive or somatoform disorders. The most frequent psychopathological symptoms are anxiety, depression and somatization. Similarly, the findings are insufficient to determine the existence of deficits in the domains of executive functioning, memory and intelligence. However, the existence of attention biases does seem to be clear. This review supposes a starting point for conceptualizing chronic primary visceral pain. It is necessary to continue further research so as to obtain a better understanding of this pathology and the disorders associated.

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Cerium Oxide Nanoparticles Alleviate Neuropathic Pain by Modulating Macrophage Polarization in a Rat SCI Model.

Chronic neuropathic pain (NP) frequently occurs after spinal cord injury (SCI) but lacks effective therapeutic options in the clinic. Numerous evidence indicates the involvement of macrophages activation in the NP, and the modulation of macrophages is promising for NP treatment. In this study, we introduce Cerium oxide nanoparticles (CONPs) and aim to investigate whether it can relieve the NP by modulating macrophage polarization.

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Inhibition of angiogenetic macrophages reduces disc degeneration-associated pain.

Abnormal angiogenesis and innervation in avascular discs during lumbar disc degeneration (LDD) cause severe back pain. These pathological alterations in the degenerating discs are induced by cytokines partially produced and secreted by inflammatory cells, among which macrophages are the most frequently ones detected at the legion site. However, the role of macrophages as well as their polarization in regulation of innervation and angiogenesis in the degenerating discs is unclear. In this study, we analyzed macrophages in the degenerating discs from patients and detected a specific macrophage subtype that expresses high levels of vascular endothelial growth factor A (VEGF-A). Co-expression of M2 macrophage markers in this macrophage subtype suggested that they were a M2d-like subtype. High levels of VEGF-A and genes associated with angiogenesis were also detected in LDD specimens compared to control heathy discs from a public database, consistent with our finding. Moreover, the levels of VEGF-A in disc macrophages were strongly correlated to the pain score of the examined patients, but not to the Thompson classification of the degeneration level of the patients. , overexpressing VEGF-A in macrophages increased the tube formation, proliferation and migration of co-cultured endothelial cells, and increased the innervation of embryonic spinal cord explant into the co-cultured area for macrophages and skeletal myocytes. , an orthotopic injection of adeno-associated virus carrying siRNA for VEGF-A under a macrophage-specific CD68 promoter significantly reduced the number of VEGF-A-positive disc macrophages and alleviated the pain in LDD-mice. Together, these data suggest that inhibition of angiogenetic potential of macrophages may reduce disc degeneration-associated pain through suppression of angiogenesis and innervation, as a promising therapy for LDD-associated pain.

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Classification of elderly pain severity from automated video clip facial action unit analysis: A study from a Thai data repository.

Data from 255 Thais with chronic pain were collected at Chiang Mai Medical School Hospital. After the patients self-rated their level of pain, a smartphone camera was used to capture faces for 10 s at a one-meter distance. For those unable to self-rate, a video recording was taken immediately after the move that causes the pain. The trained assistant rated each video clip for the pain assessment in advanced dementia (PAINAD). The pain was classified into three levels: mild, moderate, and severe. OpenFace was used to convert the video clips into 18 facial action units (FAUs). Five classification models were used, including logistic regression, multilayer perception, naïve Bayes, decision tree, k-nearest neighbors (KNN), and support vector machine (SVM). Out of the models that only used FAU described in the literature (FAU 4, 6, 7, 9, 10, 25, 26, 27, and 45), multilayer perception is the most accurate, at 50%. The SVM model using FAU 1, 2, 4, 7, 9, 10, 12, 20, 25, and 45, and gender had the best accuracy of 58% among the machine learning selection features. Our open-source experiment for automatically analyzing video clips for FAUs is not robust for classifying pain in the elderly. The consensus method to transform facial recognition algorithm values comparable to the human ratings, and international good practice for reciprocal sharing of data may improve the accuracy and feasibility of the machine learning's facial pain rater.

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The Prevalence of Chronic Pain in the Adult Population in Israel: An Internet-Based Survey.

Chronic pain (CP) prevalence in different studies has been inconsistent, ranging from 12% in Spain to 42% in the UK.

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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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