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Ibuprofen efficacy, tolerability and safety in obese children: a systematic review.

Childhood obesity can affect drug disposition and efficacy of ibuprofen. The primary objective was to assess efficacy of ibuprofen in obese children.

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Opioid-reduced anesthesia based on esketamine in gynecological day surgery: a randomized double-blind controlled study.

Opioid-reduced anesthesia may accelerate postoperative rehabilitation by reducing opioid-related side effects. The objective was to investigate the feasibility of opioid-reduced general anesthesia based on esketamine and to observe postoperative nausea and vomiting (PONV), postoperative pain, hemodynamics and other adverse reactions in gynecological day surgery compared with the traditional opioid-based anesthesia program.

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Associations of poor sleep quality, chronic pain and depressive symptoms with frailty in older patients: is there a sex difference?

Sleep disturbance, chronic pain and depressive symptoms later in life are modifiable risk factors and may contribute to frailty. However, much less is known about sex differences in the association between these concurrent symptoms and frailty in older patients. Therefore, we conducted this study to explore the associations of poor sleep quality, chronic pain, and depressive symptoms with frailty in older patients, and the sex-specific associations.

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Pitavastatin attenuates neuropathic pain induced by partial sciatic nerve in Wistar rats.

Pitavastatin is a competitive HMG-CoA reductase inhibitor for lowering of cholesterol level and low density lipoprotein cholesterol. This study was designed to evaluate the effect of pitavastatin in neuropathic pain induced by partial sciatic nerve ligation along with neuronal changes in Wister rats.

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Morphine upregulates Toll-like receptor 4 expression and promotes melanomas in mice.

Morphine and other opioids are used to manage cancer-related pain; however, the role of these drugs in cancer progression remains controversial. Emerging evidence indicates that morphine can activate Toll-like receptor 4 (TLR4) and its signaling pathways, by the way the activation and expression of TLR4 can promote melanoma. In this study, we investigated the effects of morphine on the expression of TLR4 and promotion of melanoma in mice.

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Peri-operative management of neuromuscular blockade: A guideline from the European Society of Anaesthesiology and Intensive Care.

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient's outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research (n = 24 000) to the finally relevant clinical studies (n = 88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg kg-1 or rocuronium 0.9 to 1.2 mg kg-1 (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications. (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i.e. TOF ratio >0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained. (1C).

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The Emerging Pro-Algesic Profile of Transient Receptor Potential Vanilloid Type 4.

Transient receptor potential vanilloid type 4 (TRPV4) channels are Ca-permeable non-selective cation channels which mediate a wide range of physiological functions and are activated and modulated by a diverse array of stimuli. One of this ion channel's least discussed functions is in relation to the generation and maintenance of certain pain sensations. However, in the two decades which have elapsed since the identification of this ion channel, considerable data has emerged concerning its function in mediating pain sensations. TRPV4 is a mediator of mechanical hyperalgesia in the various contexts in which a mechanical stimulus, comprising trauma (at the macro-level) or discrete extracellular pressure or stress (at the micro-level), results in pain. TRPV4 is also recognised as constituting an essential component in mediating inflammatory pain. It also plays a role in relation to many forms of neuropathic-type pain, where it functions in mediating mechanical allodynia and hyperalgesia.Here, we review the role of TRPV4 in mediating pain sensations.

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Analgesic tolerance and cross-tolerance to the bifunctional opioid/neuropeptide FF receptors agonist EN-9 and μ-opioid receptor ligands at the supraspinal level in mice.

The chimeric peptide EN-9 was reported as a κ-opioid/neuropeptide FF receptors bifunctional agonist that modulated chronic pain with no tolerance. Many lines of evidence have shown that the effect of the κ-opioid receptor is mediated by not only its specific activation but also downstream events participation, especially interaction with the μ-opioid receptor pathway in antinociception and tolerance on most occasions. The present study investigated the acute and chronic cross-tolerance of EN-9 with μ-opioid receptor agonist EM-2, DAMGO, and morphine after intracerebroventricularly (i.c.v) injection in the mouse tail-flick test. In the acute tolerance test, EN-9 showed symmetrical acute cross-tolerance to DAMGO but no cross-tolerance to EM2. In the chronic tolerance test, EN-9 had no tolerance after eight days of repeated administration. However, EN-9 illustrated complete cross-tolerance to morphine and symmetrical cross-tolerance to EM2. In addition, inhibition of NPFF receptor could induce the tolerance development of EN-9. These findings indicated that supraspinal EN-9-induced antinociception contains additional components, which are mediated by the downstream μ-opioid receptor pathway both in acute and chronic treatment, whereas the subtypes of μ-opioid receptor or NPFF system pathway involved in antinociceptive effects induced by EN-9 are complex. Identifying the receptor mechanism could help design preferable bifunctional opioid compounds.

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Pulsed Radiofrequency for the Treatment of Trigeminal Neuralgia.

Trigeminal neuralgia is a sudden, unilateral, stabbing pain in the distribution of one or more branches of the fifth cranial nerve, with an overall prevalence ranging between 0.03 and 0.3%. While conservative treatments may offer temporary relief, many patients experience chronic headaches associated with their neuralgia. Invasive treatments are available for patients with intractable neuralgia; however, they may cause permanent tissue damage and often do not provide relief. This article examines pulsed radiofrequency (PRF) ablation (RFA) of the trigeminal nerve as a minimally invasive procedure that offers a promising alternative to invasive procedures for relief of trigeminal neuralgia while minimizing tissue damage.

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Trigeminal afferents sense locomotion-related meningeal deformations.

The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice. Surprisingly, a large subset of afferents was activated during non-noxious conditions such as locomotion. We estimated locomotion-related meningeal deformations and found afferents with distinct dynamics and tuning to various levels of meningeal expansion, compression, shearing, and Z-axis motion. Further, these mechanosensitive afferents were often tuned to distinct directions of meningeal expansion or compression. Thus, in addition to their role in headache-related pain, meningeal sensory neurons track the dynamic mechanical state of the meninges under natural conditions.

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