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Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.
Gudbergsen, H, Overgaard, A, Henriksen, M, Wæhrens, EE, Bliddal, H, Christensen, R, Nielsen, SM, Boesen, M, Knop, FK, Astrup, A, et al
The American journal of clinical nutrition. 2021;(2):314-323
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Abstract
BACKGROUND Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.
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Lamiaceae in Mexican Species, a Great but Scarcely Explored Source of Secondary Metabolites with Potential Pharmacological Effects in Pain Relief.
Hernandez-Leon, A, Moreno-Pérez, GF, Martínez-Gordillo, M, Aguirre-Hernández, E, Valle-Dorado, MG, Díaz-Reval, MI, González-Trujano, ME, Pellicer, F
Molecules (Basel, Switzerland). 2021;(24)
Abstract
The search for molecules that contribute to the relief of pain is a field of research in constant development. Lamiaceae is one of the most recognized families world-wide for its use in traditional medicine to treat diseases that include pain and inflammation. Mexico can be considered one of the most important centers of diversification, and due to the high endemism of this family, it is crucial for the in situ conservation of this family. Information about the most common genera and species found in this country and their uses in folk medicine are scarcely reported in the literature. After an extensive inspection in bibliographic databases, mainly Sciencedirect, Pubmed and Springer, almost 1200 articles describing aspects of Lamiaceae were found; however, 217 articles were selected because they recognize the Mexican genera and species with antinociceptive and/or anti-inflammatory potential to relieve pain, such as Salvia and Agastache. The bioactive constituents of these genera were mainly terpenes (volatile and non-volatile) and phenolic compounds such as flavonoids (glycosides and aglycone). The aim of this review is to analyze important aspects of Mexican genera of Lamiaceae, scarcely explored as a potential source of secondary metabolites responsible for the analgesic and anti-inflammatory properties of these species. In addition, we point out the possible mechanisms of action involved and the modulatory pathways investigated in different experimental models. As a result of this review, it is important to mention that scarce information has been reported regarding species of this family from Mexican genera. In fact, despite Calosphace being one of the largest subgenera of Salvia in the world, found mainly in Mexico, it has been barely investigated regarding its potential biological activities and recognized bioactive constituents. The scientific evidence regarding the different bioactive constituents found in species of Lamiaceae demonstrates that several species require further investigation in preclinical studies, and of course also in controlled clinical trials evaluating the efficacy and safety of these natural products to support their therapeutic potential in pain relief and/or inflammation, among other health conditions. Since Mexico is one of the most important centers of diversification, and due to the high endemism of species of this family, it is crucial their rescue, in situ conservation, and investigation of their health benefits.
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Prioritizing Pain-Associated Targets with Machine Learning.
Jeon, M, Jagodnik, KM, Kropiwnicki, E, Stein, DJ, Ma'ayan, A
Biochemistry. 2021;(18):1430-1446
Abstract
While hundreds of genes have been associated with pain, much of the molecular mechanisms of pain remain unknown. As a result, current analgesics are limited to few clinically validated targets. Here, we trained a machine learning (ML) ensemble model to predict new targets for 17 categories of pain. The model utilizes features from transcriptomics, proteomics, and gene ontology to prioritize targets for modulating pain. We focused on identifying novel G-protein-coupled receptors (GPCRs), ion channels, and protein kinases because these proteins represent the most successful drug target families. The performance of the model to predict novel pain targets is 0.839 on average based on AUROC, while the predictions for arthritis had the highest accuracy (AUROC = 0.929). The model predicts hundreds of novel targets for pain; for example, GPR132 and GPR109B are highly ranked GPCRs for rheumatoid arthritis. Overall, gene-pain association predictions cluster into three groups that are enriched for cytokine, calcium, and GABA-related cell signaling pathways. These predictions can serve as a foundation for future experimental exploration to advance the development of safer and more effective analgesics.
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The Analgesic Properties of Corydalis yanhusuo.
Alhassen, L, Dabbous, T, Ha, A, Dang, LHL, Civelli, O
Molecules (Basel, Switzerland). 2021;(24)
Abstract
Corydalis yanhusuo extract (YHS) has been used for centuries across Asia for pain relief. The extract is made up of more than 160 compounds and has been identified as alkaloids, organic acids, volatile oils, amino acids, alcohols, and sugars. However, the most crucial biological active constituents of YHS are alkaloids; more than 80 have been isolated and identified. This review paper aims to provide a comprehensive review of the phytochemical and pharmacological effects of these alkaloids that have significant ties to analgesia.
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Analgesic effects of breast- and formula feeding during routine childhood immunizations up to 1 year of age.
Viggiano, C, Occhinegro, A, Siano, MA, Mandato, C, Adinolfi, M, Nardacci, A, Caiazzo, AL, Viggiano, D, Vajro, P
Pediatric research. 2021;(5):1179-1184
Abstract
BACKGROUND Data on analgesic effects of breast/formula milk sucking while receiving routine childhood immunizations are available only in early infancy, have rarely been compared in the same study, and are not accompanied by information on mothers' satisfaction/acceptance. Here we aimed to compare the analgesic effect of both methods vs. held-only controls up to 1 year of age, and verify mothers' satisfaction. METHODS Two to 12 months children subjected to vaccine were allocated into three groups: breastfed, formula-fed, and held-only controls. A video recording was performed to analyze pain parameters: crying latency/duration and specific scales [FLACC (Face, Legs, Activity, Cry, and Consolability), NIPS (Neonatal Infant Pain Scale)]. After the procedure, mothers filled in a satisfaction questionnaire. RESULTS One-hundred and sixty-two children were recruited: 54 breastfed, 35 formula fed, and 73 controls. Breastfed showed the longest crying latency, and together with formula fed, had the shortest duration and lowest pain scores. Most mothers appreciated not only the respective feeding-mediated pain mitigation method used, but also the simply-holding procedure. In all cases, they felt reassured, with an unexpected frequent underestimation of their child's pain during the shot. CONCLUSIONS The analgesic effect of breastfeeding during vaccination extends also to children >6 months old, and is obtained by formula too. Embracing the child may help to reassure mothers. IMPACT We confirmed the analgesic effect of breastfeeding during the vaccination procedures in early infancy. We show for the first time that this effect is extended also to children up to 1 year of age, and it may be obtained by formula feeding as well. Most mothers appreciated pain mitigation not only through feeding, but also the simply-holding procedure. In all cases, mothers felt reassured, with an unexpected frequent underestimation of their child' pain during the shot. The promotion of these easily feasible and well-accepted strategies should be further encouraged within health professionals during vaccination procedures.
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Neuropathic and Psychogenic Components of Burning Mouth Syndrome: A Systematic Review.
Orliaguet, M, Misery, L
Biomolecules. 2021;(8)
Abstract
The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogenic components of primary BMS for a better understanding of the disease. This systematic review (SR) was registered in PROSPERO (CRD42021224160). The search was limited to articles in English or French from 1990 to 01 December 2020. A total of 113 articles were considered for data extraction. We divided them into four subgroups: pharmacological and nonpharmacological management studies (n = 23); neurophysiological studies (n = 35); biohistopathological studies (n = 25); and questionnaire-based studies (n = 30). Several of these studies have shown neuropathic involvement at various levels of the neuraxis in BMS with the contribution of quantitative sensory testing (QST), functional brain imaging, and biohistopathological or pharmacologic studies. On the other hand, the role of psychological factors in BMS has also been the focus of several studies and has shown a link with psychiatric disorders such as anxiety and/or depression symptoms. Depending on the patient, the neuropathic and psychogenic components may exist simultaneously, with a preponderance of one or the other, or exist individually. These two components cannot be dissociated to define BMS. Consequently, BMS may be considered nociplastic pain.
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An Investigation into the Effects of a Curcumin Extract (Curcugen®) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study.
Lopresti, AL, Smith, SJ, Jackson-Michel, S, Fairchild, T
Nutrients. 2021;(1)
Abstract
Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen®) or placebo. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee pain ratings, Japanese Orthopaedic Association Score for Osteoarthritic Knees (JOA), PROMIS-29, and performance-based testing comprising the 40-m fast-paced walk test, 6-min walk test, timed up-and-go test, and 30-s chair stand test. Compared to the placebo, curcumin significantly reduced the KOOS knee pain score (p = 0.009) and numeric knee pain ratings (p = 0.001). Curcumin was also associated with greater improvements (p ≤ 0.05) than the placebo on the timed up-and-go test, 6-min walk test, and the JOA total score; but not the 30-s chair stand test or 40-m fast-paced walk test. Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo. The findings support the potential efficacy of curcumin for the treatment of osteoarthritis of the knee but studies of longer duration, varying treatment doses, differing curcumin extracts, and the use of other objective outcome measures will be helpful to expand on these findings.
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Ibuprofen Safety at the Golden Anniversary: Are all NSAIDs the Same? A Narrative Review.
Varrassi, G, Pergolizzi, JV, Dowling, P, Paladini, A
Advances in therapy. 2020;(1):61-82
Abstract
Ibuprofen first came to market about 50 years ago and rapidly moved to over-the-counter (OTC) sales. In April 2019, the National Agency for the Safety of Medicines and Health Products (ANSM) of France issued a warning for NSAID uses by patients with infectious diseases based on an analysis of 20 years of real-world safety data on ibuprofen and ketoprofen. Nevertheless, ibuprofen remains a mainstay in the analgesic armamentarium and with numerous randomized clinical trials, head-to-head studies, and decades of clinical experience. The authors offer a review of the safety of ibuprofen and how it may differ from other NSAIDs. Ibuprofen is associated with certain well-known gastrointestinal adverse effects that are related to dose and patient population. Among nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen has a comparatively low risk of cardiovascular adverse effects. It has been associated with renal and hepatic adverse effects, which appear to depend on dose, concomitant medications, and patient population. The association of ibuprofen with infections is more complex in that it confers risk in some situations but benefits in others, the latter in cystic fibrosis. Emerging interest in the literature is providing evidence of the role of ibuprofen as a possible endocrine disrupter as well as its potential antiproliferative effects for cancer cells. Taken altogether, ibuprofen has a favorable safety profile and is an effective analgesic for many acute and chronic pain conditions, although it-like other NSAIDs-is not without risk. After 50 years, evidence is still emerging about ibuprofen and its unique safety profile among NSAIDs. FUNDING The Rapid Service Fee was funded by Abbott Established Pharmaceuticals Division (EPD).
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The effect of aromatherapy with rose and lavender on anxiety, surgical site pain, and extubation time after open-heart surgery: A double-center randomized controlled trial.
Babatabar Darzi, H, Vahedian-Azimi, A, Ghasemi, S, Ebadi, A, Sathyapalan, T, Sahebkar, A
Phytotherapy research : PTR. 2020;(10):2675-2684
Abstract
To determine the effect of aromatherapy with rose and lavender on the patient outcomes after open-heart surgery (OHS). In the clinical trial, patients were randomized to four groups. One group received routine care, the placebo group received a cotton swab soaked in water and the other two groups received either a cotton swab containing three drops of rose or lavender essence (0.2 ml). A total of 160 patients were randomized into four groups. Intergroup anxiety was not significantly different; however, the reciprocal time-group effect was significant among the four groups. The extubation time was significant among the four groups which related to rose essence group compared with the control group (p < .001) and placebo group (p = .029). The surgical site pain was significant in the rose essence and lavender groups compared to the control group. Aromatherapy can reduce extubation time, surgical site pain severity, and anxiety in patients undergoing OHS.
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Effect of nipple shield use on milk removal: a mechanistic study.
Coentro, VS, Perrella, SL, Lai, CT, Rea, A, Murray, K, Geddes, DT
BMC pregnancy and childbirth. 2020;(1):516
Abstract
BACKGROUND Concerns about reduced milk transfer with nipple shield (NS) use are based on evidence from studies with methodological flaws. Milk removal during breastfeeding can be impacted by infant and maternal factors other than NS use. The aim of this study was to control electric breast pump vacuum strength, pattern and duration across multiple study sessions to determine if NS use reduces milk removal from the breast. METHODS A within-subject study with two groups of breastfeeding mothers (infants < 6 months) were recruited; Control Group (CG): no breastfeeding difficulties; Pain Group (PG) used NS for persistent nipple pain. Mothers completed three randomised 15 min pumping sessions using the Symphony vacuum curve (Medela AG); no NS, fitted NS, and a small NS. Sessions were considered valid where the applied vacuum was within 20 mmHg of the set vacuum. Milk removal was considered as pumped milk volume, and also percentage of available milk removed (PAMR), which is calculated as the pumped volume divided by the estimated milk volume stored in the breast immediately prior to pumping. RESULTS Of 62 sessions (all: n = 31 paired sessions) a total of 11 paired sessions from both PG (n = 03) and CG (n = 08) were valid (subset) with and without a fitted NS. Only 2 small shield sessions were valid and so all small shield measurements were excluded. Both pumped volumes and PAMR were significantly lower with NS use for all data but not for subset data. (All: Volume and PAMR median: no NS: 76.5 mL, 69%, Fitted NS: 32.1 mL, 41% respectively (volume p = 0.002, PAMR p = 0.002); Subset: Volume and PAMR median: no NS: 83.8 mL, 72%; Fitted NS: 35.2 mL, 40% (volume p = 0.111 and PAMR p = 0.045). The difference in PAMR, but not volume, was statistically significant when analysed by linear mixed modelling. A decrease of 10 mmHg was associated with a 4.4% increase in PAMR (p = 0.017). CONCLUSIONS This experimental data suggests that nipple shield use may reduce milk removal. Close clinical monitoring of breastfeeding mothers using nipple shields is warranted.