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Byline: Min. Zhao, Jionglin. Wu, Fengtao. Ji, Deng. Li, Jichao. Ye, Zheyu. Wang, Yanni. Fu, Lin. Huang, Liangbin. Gao Background: Multimodal intraoperative monitoring (MIOM) is a useful tool to warn [...]

The purpose of this study was to explore the protective effect of BW373U86 (a [delta]-opioid receptor (DOR) agonist) on ischemia-reperfusion (I/R) injury in rat cardiomyocytes and its underlying mechanism. Primary rat cardiomyocytes were cultured and pretreated with BW373U86 for intervention. The cardiomyocytes were cultured under the condition of 94% [N.sub.2] and 5% C[O.sub.2] for 24 h to perform hypoxia culture and conventionally cultured for 12 h to perform reoxygenation culture. The cell viability of cardiomyocytes was detected by an MTT assay (Sigma-Aldrich). The autophagy lysosome levels in cardiomyocytes were evaluated by acidic vesicular organelles with dansylcadaverine (MDC) staining (autophagy test kit, Kaiji Biology, kgatg001). The protein expression levels of LC3, p62, and factors in the PI3K/Akt/mTOR signaling pathway were detected by Western blot. Pretreatment with BW373U86 could improve the cell viability of cardiomyocytes with hypoxia-reoxygenation (H/R) injury (p < 0.05). Interestingly, after coculture of BW373U86 and PI3K inhibitor (3-methyladenine), the protein expression levels of p-Akt in cardiomyocytes were markedly increased in comparison with those in the BW373U86 group (p < 0.05). However, there were no significant differences in the protein expression levels of mTOR between the coculture group and the BW373U86 group (p > 0.05). BW373U86 upregulated autophagy to protect cardiomyocytes from H/R injury, which may be related to the PI3K/Akt/m TOR pathway. Key words: hypoxia-reoxygenation injury, cardiomyocytes, BW373U86, PI3K/Akt/m TOR pathway. Cette etude avait pour but d'explorer l'effet protecteur du BW373U86 (un agoniste des recepteurs aux opiaces [delta] (ROD)) sur les lesions d'ischemie-reperfusion (I/R) dans des cardiomyocytes de rat, ainsi que son mode d'action sousjacent. Nous avons cultive des cardiomyocytes primitifs de rat et exposes au prealable au BW373U86 comme intervention. Nous avons cultive les cardiomyocytes sous des condition de [N.sub.2] a 94 % et de C[O.sub.2] a 5 % pendant 24 h afin d'obtenir une culture en hypoxie et de maniere conventionnelle pendant 12 h afin d'obtenir une culture en reoxygenation. Nous avons etabli la viabilite des cellules a l'aide de l'epreuve MTT (Sigma-Aldrich). Nous avons evalue les taux d'autophagie lysosome dans les cardiomyocytes avec des organites vesiculaires acides a l'aide de la coloration par la dansylcadaverine (MDC) (trousse d'epreuve autophagy, Kaiji Biology, kgatg001). Nous avons detecte les taux d'expression en proteines du LC3, du p62 et de facteurs de la voie de signalisation PI3K/Akt/mTOR a l'aide de l'immunobuvardage de western. L'exposition prealable au BW373U86 permettait d'ameliorer la viabilite des cardiomyocytes touches par des lesions d'hypoxie-reoxygenation (H/R) (p < 0,05). Il est interessant de noter qu'apres la culture conjointe avec le BW373U86 et un inhibiteur de la PI3K (3-methyladenine), les taux d'expression en proteines de la p-Akt dans les cardiomyocytes augmentaient de facon plus marquee que dans le groupe BW373U86 (p < 0,05). Cependant, nous n'avons pas observe de difference appreciable des taux d'expression en proteines de la mTOR entre le groupe en culture conjointe et le groupe BW373U86 (p > 0,05). En conclusion, le BW373U86 entrainait une regulation a la hausse de l'autophagie permettant de proteger les cardiomyocytes contre les lesions d'H/R, phenomene qui pourrait etre lie a la voie de signalisation PI3K/Akt/mTOR. [Traduit par la Redaction] Mots-cles: lesions d'hypoxie-reoxygenation, cardiomyocytes, BW373U86, voie de signalisation PI3K/Akt/mTOR., Introduction Ischemic heart disease has high morbidity and mortality, with acute myocardial infarction having the highest disability and mortality rates (Moran et al. 2014; Hausenloy and Yellon 2013). Currently, although [...]

Byline: Sandeep. Muzumder, S. Nirmala, H. Avinash, M. Sebastian, Prashanth. Kainthaje Aim: The aim of the study is to find the incidence of analgesic and opioid use in pain associated [...]

Abstract Evidence suggests that children who are in pain and who present to emergency departments receive sub-optimal pain assessment and relief. Many factors contribute to this unacceptable quality of care, [...]

Purpose The purpose of our study was to compare the equipotent doses of ropivacaine and levobupivacaine for walk-out criteria and the characteristics of spinal anesthesia in inguinal herniorrhaphy surgery. Methods Combined spinal-epidural anesthesia was performed. Adult patients were randomly allocated to receive 5 mg 0.5% ropivacaine plus 25 [micro]g fentanyl (group RF, n = 25) or 3.75 mg 0.75% levobupivacaine plus 25 [micro]g fentanyl (group LF, n = 25). Each solution was hypobaric, and the same volume, 3 ml, was administered. Sensory and motor block characteristics, hemodynamic changes, side effects, number of patients having ability to stand and walk at the end of the operation, time to first analgesic requirement, time to urination, time to getting out of bed (ambulation), and time to home discharge were determined. Results Sensory block onset time and time to reach the T6 dermatome were significantly shorter in group LF, whereas time to the two-segment regression and time to first analgesic requirement were significantly shorter in group RF. All patients in group LF were Bromage 0. Time to home discharge was shorter in group LF, but this difference was not statistically significant. Conclusion We suggest that both local anesthetics can be used in walking spinal technique. Levobupivacaine may be an alternative local anesthetic for walking spinal anesthesia as it provides minimum motor block and a long duration of postoperative analgesia, even if its use is not associated with a shorter home discharge time. Keywords Walking spinal * Ropivacaine * Levobupivacaine, Introduction 'Walking spinal' is a new regional anesthesia technique that became popular after the selective spinal anesthesia (SSA) methods were developed. Ganapathy [1] improved SSA so that the patients could [...]

Summary The UK population is ageing and a significant proportion of older people experience persistent pain. However, pain assessment in this group can be challenging, particularly when the older person [...]

Summary This article, the sixth in a series on pain, aims to provide nurses with information about neuropathic pain, its causes, clinical presentation and treatment approaches, to assist in the [...]

Endogenous opioids generate analgesic signals in the periaqueductal gray (PAG). However, because cell types in the PAG are difficult to identify, its neuronal mechanism has remained poorly understood. To address this issue, we characterized PAG neurons by their electrical properties using differentially labeled GABAergic and output neurons in the PAG. We found that GABAergic neurons were mostly fast-spiking cells and could be further divided into two distinct classes: with or without low-threshold spikes (LTS) driven by T-type channels. In contrast, the PAG output neurons lacked LTS and showed heterogeneous firing patterns. To reveal the function of the LTS, we examined the mutant mice lacking the [alpha]1G T-type channels ([alpha][1.sup.G-/-]). The mutant mice lacked LTS in the fast-spiking GABAergic neurons of the PAG and unexpectedly showed impaired opioid-dependent analgesia; a similar phenotype was reproduced in PAG-specific [alpha]1G-knockdown mice. Electrophysiological analyses revealed functional expression of [mu]-opioid receptors in the low threshold-spiking GABAergic neurons. These neurons in the mutant lacking LTS showed markedly enhanced discharge activities, which led to an augmented inhibition of output neurons. Furthermore, the impaired analgesia observed in [alpha]1[G.sup.-/-] mice was reversed by blocking local [GABA.sub.A] receptors. These results indicate that [alpha]1G T-type channels are critical for the opioidergic descending analgesia system in the PAG. opioid-descending analgesia | [alpha]1G | morphine | stress | calcium-activated potassium channel | afterhyperpolarization doi/ 10.1073/pnas.1009532107

Byline: Nectaria Xirouchaki (1), Eumorfia Kondili (1), Maria Klimathianaki (1), Dimitris Georgopoulos (1) Keywords: Ventilator settings; Sedatives; Analgesics; Vasoactive medications; Critically ill Abstract: Objectives The aim of this study was to compare the number of interventions (ventilator settings and sedatives, analgesics and vasoactive medication dose manipulations) between critically ill patients on proportional-assist ventilation with load-adjustable gain factors (PAV+) and those on pressure support (PS). Design Retrospective analysis of data from a previous randomized clinical trial. Methods A total of 208 patients who were mechanically ventilated on controlled modes and met criteria for assisted breathing were randomized to receive either PS (n = 100) or PAV+ (n = 108). Changes in ventilator settings and in the dose of sedatives, analgesics, and vasoactive medications were identified during the period in which the patients were ventilated either with PS (30.4 +- 17.4 h) or PAV+ (30.0 +- 18.1 h) and classified as changes to facilitate weaning (CFW) or changes to respond to deterioration (CD). Results The mean number of changes in ventilator settings was significantly higher with PS than that with PAV+ (10.7 +- 5.7 vs. 8.9 +- 4.6). With PS the proportion of these changes classified as CFW was significantly lower than that with PAV+ (59.8% vs. 69.2%). Dyssynchrony as a cause of CD was more likely to occur with PS than with PAV+ (42 vs. 3%). The mean number of changes in the dose of sedatives, analgesics, and vasoactive medications was higher with PS than with PAV+, the difference being significant only for sedatives (4.06 +- 3.8 vs. 2.82 +- 3.4). Conclusions Compared to PS, PAV+ is associated with fewer intervention in terms of ventilator settings and sedative dose changes. Author Affiliation: (1) Department of Intensive Care Medicine, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete, Greece Article History: Registration Date: 28/05/2009 Received Date: 19/03/2009 Accepted Date: 20/05/2009 Online Date: 16/06/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1524-2) contains supplementary material, which is available to authorized users.

Abstract In the past 30 years, significant improvements have been made in the management of children's pain, with most children receiving analgesia post-operatively. However, the amount of analgesia administered to [...]

Nonmedical use of prescription stimulants and analgesics was assessed from personal interviews with a stratified random sample of 1,253 first-year college students ages 17 to 20 attending a large public university (86% response rate). Lifetime and past-year prevalence of nonmedical use of stimulants, analgesics, or both was [19.6%.sub.wt] and [15.6%.sub.wt], respectively. Nonmedical users had significantly lower grade point averages (GPAs) in high school as compared with nonusers; in college they skipped classes more often, spent more time socializing, and spent less time studying. For example, nonmedical users of both stimulants and analgesics skipped 21% of their college classes whereas nonusers skipped 9%. Controlling for high school GPA and other factors, past-year nonmedical use independently predicted lower college GPA by the end of the first year of college; this effect was partially mediated by skipping more classes. Nonmedical users of prescription drugs comprise a high-risk group for academic problems in college.

Objective: Multiple studies conducted over many years have demonstrated that pain is poorly managed in the emergency department (ED). This phenomenon has been referred to in the medical literature as [...]

[alpha]9[alpha]10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of [alpha]9[alpha]10 nAChRs is not known. Here we show that selective block (rather than stimulation) of [alpha]9[alpha]10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of [alpha]9[alpha]10 nAChRs in the pathophysiology of peripheral nerve injury. Conus | lymphocytes | neuropathic pain | RgIA | Vc1.1

Untreated pain is a serious problem in the United States. Given the difficulties in measuring a condition that is untreated, estimates of the number of people affected vary, but most [...]

Abstract Background Effective pain management following day surgery is a challenging issue. For the majority of patients severe pain is uncommon. However, a number of patients experience considerable pain following [...]

Byline: Rita Moretti (1,2), Paola Torre (2), Antonio Bava (1), Rodolfo M. Antonello (2) Keywords: Medication abuse; Overuse; Headache; Depression; Serotonin; SSRI; Citalopram Abstract: Abstract Medication-overuse headaches are a relevant medical and social problem, for which specific treatments have not yet been defined. In patients with chronic daily headache who take analgesics every day, this headache is most likely to be caused by drugs and will vanish with abstinence. Nonetheless, there is anecdotal evidence that selective serotonin reuptake inhibitors (SSRI) are effective in chronic daily headache, because of the concomitant presence of psychiatric comorbidities (depression, anxiety, or a combination of both). Six migraineurs were admitted to the Neurology Clinic for medicationoveruse headache and associated depression, anxiety and behavioural changes. Treatment consisted in suppressing other drugs and by using an SSRI, citalopram, at modest dosage (a$?30 mg daily). Analgesic withdrawal was performed in hospital and was not particularly problematic. Over a 1-year follow-up, pain coping strategies ameliorated and depression decreased drug withdrawal was easy, even from barbiturates, and pain control was good. Further investigation into the possible use of citalopram or other SSRIs in medication-overuse headache is waranted. Author Affiliation: (1) Department of Physiology and Pathology, University of Trieste, Trieste, Italy (2) Department of Clinical and Neurological Medicine, Neurology Clinic, Cattinara Hospital, University of Trieste, I-34149, Trieste, Italy Article History: Registration Date: 01/01/2003 Received Date: 08/08/2002 Accepted Date: 09/05/2003