Telehealth delivery of adapted CBT-I for insomnia in chronic pain patients: a single arm feasibility study.

Objectives: A large proportion of individuals with chronic pain experience insomnia-related symptoms which can be persistent in nature, and negatively impact one's quality of life. This single arm trial aimed to investigate the feasibility and preliminary efficacy of CBT-I, adapted for people with chronic musculoskeletal pain, delivered via telehealth. Methods: We conducted a single arm feasibility trial in which 10 adult women (M age = 50.76 years, SD = 8.03 years) with self-reported insomnia and a diagnosed chronic musculoskeletal chronic pain received six CBT-I individual treatment sessions over 6-10 weeks. Treatment was delivered via telehealth. Participants completed weekly sleep diaries, and self-reported measures of insomnia, pain, anxiety and depression pre-treatment, post-treatment, and one-month follow-up. Results: The trial yielded, high levels of compliance with intervention protocols, and affirmative feedback on satisfaction which demonstrated feasibility. The enrolment rate into the study was 37% (27 participants screened, 10 participants enrolled). The intervention was associated with statistically and clinically meaningful improvements in self-reported insomnia severity. There were statistically significant improvements in sleep efficiency, wake after sleep onset, sleep onset latency, anxiety and depression. Conclusion: Adapted CBT-I delivered via telehealth may be a feasible, acceptable, and efficacious therapeutic approach for individuals with co-existent sleep and chronic pain. Future trials should adopt a randomized design against usual care.

The 2021 NICE guidelines for assessment and management of chronic pain: A cross-sectional study mapping against a sample of 1,000* in the community.

Objectives: To characterise the prevailing pharmacological and non-pharmacological pain management strategies among adults with chronic pain, comparing these against the newly published NICE guidelines NG-193, and examine these pre-NG-193 pain management strategies in relation to pain severity, pain interference, sleep quality and mental health outcomes. Design: This study was conducted using a cross-sectional online survey study design. Setting: This study was conducted on a community-dwelling cohort. Participants: Adults aged 18+, living in the UK, with diagnosis of chronic pain by a health care professional. Main outcome measures: Primary outcomes were characterisation of the pain management strategies utilised. Secondary outcomes were related to pain severity, pain interference, sleep quality, depression and anxiety via validated self-report measures. Results: Several strategies were employed by respondents to manage their chronic pain condition including physical therapy, exercise, psychological therapy and pharmacological therapy. The data also indicated a high level of joint-care planning among patients and their clinicians. Some group differences were found in relation to pain, sleep and mental health outcomes. Conclusion: This study set a comparative starting baseline to which the efficacy of the NG-193 may be compared in future years. There is evidence that NICE recommendations are being followed for the management of chronic primary pain conditions; however, pharmacological use of opioid drugs is still reported by 47%. Despite the confirmed evidence in this study of small efficacy of chronic pain by pharmacological agent, the reduction in the use of pain relief medications be it over the counter medications or prescription opioids, as recommended by NG-193, may be slow to be adopted. The data suggest that more care provision is needed to meet the recommendations around pharmacological management and review.

Impactos da insuficiência cardíaca no sistema de saúde e previdenciário brasileiro: qual é o custo da doença? / Impacts of heart failure on the Brazilian health and pension system: what is the cost of the disease?

Objetivo: Estimar os principais custos indiretos da insuficiência cardíaca (IC) na população brasileira, sobre o sistema de saúde, o custo previdenciário e o quanto se perde em produtividade pelas complicações da doença. Métodos: Estudo ecológico desenvolvido com dados secundários, para a série histórica de 2018 a 2021, minerados do Departamento de Informática do Sistema Único de Saúde (Datasus), do Instituto Brasileiro de Geografia e Estatística (IBGE), e indicadores previdenciários coletados da Previdência Social e Instituto Nacional do Seguro Social (INSS). Resultados: Foram registrados 77.290 óbitos por IC no Brasil para o período, distribuídos uniformemente em relação ao sexo. A taxa de mortalidade foi diversificada entre as regiões brasileiras, com ênfase para Sudeste e Nordeste. As projeções indicam um gasto total de mais de R$ 1 bilhão com hospitalizações, com custo médio hospitalar de R$ 1.725,27 por pessoa. O custo médio por internação ultrapassou os R$ 2 bilhões de reais. Aproximadamente 3% das despesas federais são destinadas a pagamentos de benefícios relacionados a IC. Do total de afastamentos, 65% correspondem a homens e 35%, a mulheres, com custos que podem chegar a R$ 6 bilhões perdidos por ano. Conclusão: Os resultados sugerem um aumento do afastamento de portadores de IC da força de trabalho, o que acarreta maiores dispêndios para o sistema de saúde e pagamentos de benefícios previdenciários, como auxílio-doença e aposentadoria por incapacidade de longa duração. Este é o primeiro estudo que estima e correlaciona os dados socioepidemiológicos e os custos de saúde e previdenciários da IC no Brasil.

Objective: To estimate the main indirect costs of heart failure (HF) in the Brazilian population, on the health system, social security cost, and how much is lost in productivity due to the complications of the disease. Methods: Ecological study developed with secondary data, for the historical series from 2018 to 2021, mined from the Department of Informatics of the Unified Health System (Datasus), from the Brazilian Institute of Geography and Statistics (IBGE), and social security indicators collected from Social Security and the National Social Security Institute (INSS). Results: There were 77,290 deaths from HF in Brazil for the period, evenly distributed according to sex. The mortality rate was diversified among Brazilian regions, with emphasis on the Southeast and Northeast. Projections indicate a total expenditure of more than BRL 1 billion with hospitalizations, with an average hospital cost of BRL 1,725.27 per person. The average cost per hospitalization exceeded BRL 2 billion. Approximately 3% of federal expenditures are earmarked for IC benefit payments. Of the total number of absences, 65% correspond to men and 35% to women, with costs that can reach R$ 6 billion lost per year. Conclusion: The results suggest an increase in the removal of HF patients from the workforce, which leads to higher expenditures for the health system and payments of social security benefits, such as sick pay and retirement due to long-term disability. This is the first study that estimates and correlates socio-epidemiological data, health and social security costs of HF in Brazil.

Exploring the feasibility and acceptability of a sleep wearable headband among a community sample of chronic pain individuals: An at-home observational study.

Background: Chronic pain conditions affect up to one third of the adult population in the United Kingdom. Sleep problems are prevalent and negatively impact quality of life. Lack of standardised tools for routine screening and assessment of sleep changes have been a barrier for sleep management. Novel sleep wearables offer an exciting and accessible way to measure sleep but have not been tested outside of the consumer-led landscape and are not commonly used in research and clinical settings. Aims: The study aimed to explore the feasibility and acceptability of a sleep monitoring headband (Dreem 2) utilising EEG technology and accompanying smartphone application among a cohort of adults with chronic pain. Results: Twenty-one adults (81% women) completed a one-week home sleep study using a sleep headband and accompanying app. Ninety per cent of participants met the pre-defined requirement of two-night's sleep recording. All participants recorded one night of sleep data via the sleep headband. The majority (76%) of participants were satisfied with the sleep study, and 86% of participants were willing to wear the headband longer than the 2-night minimum requirement. Finally, 76% reported the headband as 'somewhat' or 'extremely' comfortable whist awake; 57% rated the headband as comfortable during sleep. Conclusion: The Dreem 2 headband appears to be a feasible and acceptable means of collecting sleep measurements among individuals with chronic pain, despite common sleep disturbances. These devices may have utility for screening, assessment and monitoring in research and practice. Further research is needed to provide guidelines and training for integration.

Acute impact of a national lockdown during the COVID-19 pandemic on wellbeing outcomes among individuals with chronic pain.

Changes to wellbeing in a community-based sample of 638 adults with non-malignant chronic pain were assessed during a period of mandated lockdown measures in the UK to control the COVID-19 outbreak. Participants completed an online survey pre-lockdown and were followed up during lockdown. Multivariate analysis demonstrated that decreased ability to self-manage pain, restricted access to healthcare and increased dependence on others were associated with negative wellbeing outcomes related to sleep, anxiety and depression. Essential but non-urgent services are required during periods of lockdown to maintain independence and self-management in order to preserve wellbeing in this population.

Good Sleep Quality Improves the Relationship Between Pain and Depression Among Individuals With Chronic Pain.

Individuals with chronic pain often experience co-existing sleep problems and depression-related states. Chronic pain, sleep problems, and depression interrelate, and have been shown to exacerbate one another, which negatively impacts quality of life. This study explored the relationships between pain severity, pain interference, sleep quality, and depression among individuals with chronic pain. Secondly, we tested whether sleep quality may moderate the relationship between pain and depression. A cross-sectional survey was completed by 1,059 adults with non-malignant chronic pain conditions (M age 43 years, 88% identified as women) and collected measures related to pain severity, pain interference, sleep quality, and depression. Multiple regression analyses found that pain severity, pain interference, and sleep quality are all significantly associated with depression. Secondly, moderated regression analyses revealed that sleep quality moderates the relationship between pain interference and depression among individuals with chronic pain such that good sleep quality attenuates the effect of pain interference on depression, and poor sleep quality amplifies the effect of pain interference on depression. These findings suggest that sleep quality may be a relevant therapeutic target for individuals with chronic pain and co-existing depression.

Zero-hour contracts and stress in UK domiciliary care workers.

The UK domiciliary care workers play a vital role in maintaining and improving the lives of service users who have a variety of needs. Around 60% of these employees work under zero-hours contracts but, while it is known that conditions such as temporary and shift working can influence employee health and performance, zero-hours have not been widely investigated. This project sought to first investigate the stress associated with working as a domiciliary care worker, as well as comparing the experiences of employees contracted to zero-hours with those contracted to at least 16 hr per week. Twenty-nine semistructured interviews (15 zero-hour, 14 contracted hours) were conducted in the West Midlands of the United Kingdom and analysed using thematic analysis. Across all participants, four predominant stressors were found. First, the level of pay for a job with high levels of responsibility was poor. Second, participants described struggling to maintain an adequate work-life balance due to the varied timings of visits, as well as rude and aggressive behaviour from both service users and their families. Lastly, a lack of peer support and poor care from peers was discussed. However, every respondent described the positive relationships that they develop with service users being a distinct stress reliever. Zero-hours respondents discussed two further stressors. Power refers to the relationship between employee and management, with respondents describing the balance of power being with the management. Uncertainty reflected respondents not having set hours of work or pay, and thus not being able to plan their personal lives and sometimes not being able to pay bills. Findings suggest that domiciliary care workers are exposed to a range of stressors, with zero-hours adding to these. Further research should look into methods to improve both the job role for workers, and redress the power relationships for those with zero-hours contracts.

Pain expressiveness and altruistic behavior: an exploration using agent-based modeling.

Predictions which invoke evolutionary mechanisms are hard to test. Agent-based modeling in artificial life offers a way to simulate behaviors and interactions in specific physical or social environments over many generations. The outcomes have implications for understanding adaptive value of behaviors in context. Pain-related behavior in animals is communicated to other animals that might protect or help, or might exploit or predate. An agent-based model simulated the effects of displaying or not displaying pain (expresser/nonexpresser strategies) when injured and of helping, ignoring, or exploiting another in pain (altruistic/nonaltruistic/selfish strategies). Agents modeled in MATLAB interacted at random while foraging (gaining energy); random injury interrupted foraging for a fixed time unless help from an altruistic agent, who paid an energy cost, speeded recovery. Environmental and social conditions also varied, and each model ran for 10,000 iterations. Findings were meaningful in that, in general, contingencies that evident from experimental work with a variety of mammals, over a few interactions, were replicated in the agent-based model after selection pressure over many generations. More energy-demanding expression of pain reduced its frequency in successive generations, and increasing injury frequency resulted in fewer expressers and altruists. Allowing exploitation of injured agents decreased expression of pain to near zero, but altruists remained. Decreasing costs or increasing benefits of helping hardly changed its frequency, whereas increasing interaction rate between injured agents and helpers diminished the benefits to both. Agent-based modeling allows simulation of complex behaviors and environmental pressures over evolutionary time.

O papel da solidariedade intergeracional no âmbito da literacia digital / The role of intergenerational solidarity in digital literacy

No âmbito do envelhecimento e aposta na aprendizagem intergeracional para desenvolver a literacia digital, este trabalho recorre à Teoria da Ação Planeada para analisar a intenção de jovens universitários ajudarem idosos a adquirirem competências digitais. Com aplicação de questionário a 135 estudantes, os resultados enfatizam a promoção de estratégias educacionais pró-sociais que reforcem o valor da solidariedade e o desenho de programas significativos para ambas as gerações.(AU)

In the context of ageing and the need to focus on intergenerational learning to develop digital literacy, this study applies the Theory of Planned Behaviour to analyse university student’s intentions to help seniors acquire digital skills. We applied a questionnaire to 135 students and the results enphasise the need to promote educacional pro-social strategies to enhance the value of solidarity and designing meaningful activities for both generations.(AU)

O papel da solidariedade intergeracional no âmbito da literacia digital / The role of intergenerational solidarity in digital literacy

No âmbito do envelhecimento e aposta na aprendizagem intergeracional para desenvolver a literacia digital, este trabalho recorre à Teoria da Ação Planeada para analisar a intenção de jovens universitários ajudarem idosos a adquirirem competências digitais. Com aplicação de questionário a 135 estudantes, os resultados enfatizam a promoção de estratégias educacionais pró-sociais que reforcem o valor da solidariedade e o desenho de programas significativos para ambas as gerações.

In the context of ageing and the need to focus on intergenerational learning to develop digital literacy, this study applies the Theory of Planned Behaviour to analyse university student’s intentions to help seniors acquire digital skills. We applied a questionnaire to 135 students and the results enphasise the need to promote educacional pro-social strategies to enhance the value of solidarity and designing meaningful activities for both generations.

Experimental insights into age-exacerbated cognitive dysfunction after peripheral surgery.

Here I comment on the recent contribution by Barrientos et al. J. Neurosci. 32, 14641-14648 (2012) addressing treatment possibilities for surgery-induced cognitive dysfunction. It has been over 15 years since the publication of a landmark study that indicated age as a major risk factor for postoperative cognitive dysfunction (POCD) (Moller et al., Lancet 351, 857-861 1998). With increasing life expectancy, surgical procedures conducted in elderly persons are becoming more common. The prevalence of POCD may mean that some patients will exchange the incapacitating condition that led them to surgery in the first instance for another such condition, which has been created by the surgical procedure itself. The report by Barrientos and collaborators (2012) is a timely and welcome study that further examines treatment possibilities for surgery-induced cognitive dysfunction. Future studies should address issues such as intensity and onset of inflammation within the brain and additional treatments possibilities beyond IL-1-ra.

The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats.

OBJECTIVE: Xenon provides neuroprotection in multiple animal models; however, little is known about the other noble gases. The aim of the current study was to compare xenon, argon, and helium neuroprotection in a neonatal asphyxia model in rats. DESIGN: Randomized controlled trial. SETTING: Laboratory. SUBJECTS: Seven-day-old postnatal Sprague-Dawley rats. INTERVENTIONS: Seventy percent argon, helium, xenon, or nitrogen balanced with oxygen after hypoxic-ischemic brain injury. MEASUREMENTS AND MAIN RESULTS: Control animals undergoing moderate hypoxic-ischemia endured reduced neuronal survival at 7 days with impaired neurologic function at the juvenile age compared with naïve animals. Severe hypoxic-ischemic damage produced a large cerebral infarction in controls. After moderate hypoxic-ischemia, all three noble gases improved cell survival, brain structural integrity, and neurologic function on postnatal day 40 compared with nitrogen. Interestingly, argon improved cell survival to naïve levels, whereas xenon and helium did not. When tested against more severe hypoxic-ischemic injury only, argon and xenon reduced infarct volume. Furthermore, postinjury body weight in moderate insult was lower in the helium-treated group compared with the naïve, control, and other noble gas treatment groups, whereas in the severe injurious setting, it is lower in both control and helium-treated groups than other groups. In the nondirectly injured hemisphere, argon, helium, and xenon increased the expression of Bcl-2, whereas helium and xenon increased Bcl-xL. In addition, Bax expression was enhanced in the control and helium groups. CONCLUSIONS: These studies indicate that argon and xenon provide neuroprotection against both moderate and severe hypoxia-ischemic brain injury likely through prosurvival proteins synthesis.

Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.

It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the future.

Systemic inflammation enhances surgery-induced cognitive dysfunction in mice.

The activation of the immune system, by either lipopolysaccharide (LPS) administration or surgical trauma, has been shown to be capable of affecting hippocampal function, causing memory impairment. Here, we examined the extent to which LPS-induced infection may aggravate impairment of memory function following orthopaedic surgery. Hippocampal memory function impairment was assessed using fear-conditioning tasks, while IL-1ß levels in plasma and hippocampus were measured using ELISA. LPS-induced inflammation disrupted hippocampal memory consolidation as evidenced by reduced contextual freezing time exhibited by infected mice. Likewise, surgery caused hippocampal-dependent memory impairment, which was associated with increased levels of IL-1ß both in plasma and hippocampus. However, a sub-pyrogenic dose of LPS alone failed to impair memory function. This dose of LPS, when administered prior to surgery, exacerbated surgery-induced cognitive dysfunction as evidenced by further reduction of contextual freezing time. Also, it caused a concomitant additional increase in the levels of IL-1ß in both plasma and hippocampus of those animals. Our data suggest that sub-clinical infection may sensitise the immune system augmenting the severity of post-operative cognitive dysfunction.

Severe burn injury induces a characteristic activation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons.

We have studied scalding-type burn injury-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the spinal dorsal horn, which is a recognised marker for spinal nociceptive processing. At 5min after severe scalding injury to mouse hind-paw, a substantial number of phosphorylated ERK1/2 (pERK1/2) immunopositive neurons were found in the ipsilateral dorsal horn. At 1h post-injury, the number of pERK1/2-labelled neurons remained substantially the same. However, at 3h post-injury, a further increase in the number of labelled neurons was found on the ipsilateral side, while a remarkable increase in the number of labelled neurons on the contralateral side resulted in there being no significant difference between the extent of the labelling on both sides. By 6h post-injury, the number of labelled neurons was reduced on both sides without there being significant difference between the two sides. A similar pattern of severe scalding injury-induced activation of ERK1/2 in spinal dorsal horn neurons over the same time-course was found in mice which lacked the transient receptor potential type 1 receptor (TRPV1) except that the extent to which ERK1/2 was activated in the ipsilateral dorsal horn at 5 min post-injury was significantly greater in wild-type animals when compared to TRPV1 null animals. This difference in activation of ERK1/2 in spinal dorsal horn neurons was abolished within 1h after injury, demonstrating that TRPV1 is not essential for the maintenance of ongoing spinal nociceptive processing in inflammatory pain conditions in mouse resulting from at least certain types of severe burn injury.

Extracellular signal-regulated kinases in pain of peripheral origin.

Activation of members of the family of enzymes known as extracellular signal-regulated kinases (ERKs) is now known to be involved in the development and/or maintenance of the pain associated with many inflammatory conditions, such as herniated spinal disc pain, chronic inflammatory articular pain, and the pain associated with bladder inflammation. Moreover, ERKs are implicated in the development of neuropathic pain signs in animals which are subjected to the lumbar 5 spinal nerve ligation model and the chronic constriction injury model of neuropathic pain. The position has now been reached where all scientists working on pain subjects ought to be aware of the importance of ERKs, if only because certain of these enzymes are increasingly employed as experimental markers of nociceptive processing. Here, we introduce the reader, first, to the intracellular context in which these enzymes function. Thereafter, we consider the involvement of ERKs in mediating nociceptive signalling to the brain resulting from noxious stimuli at the periphery which will be interpreted by the brain as pain of peripheral origin.

Role of interleukin-1beta in postoperative cognitive dysfunction.

OBJECTIVE: Although postoperative cognitive dysfunction (POCD) often complicates recovery from major surgery, the pathogenic mechanisms remain unknown. We explored whether systemic inflammation, in response to surgical trauma, triggers hippocampal inflammation and subsequent memory impairment, in a mouse model of orthopedic surgery. METHODS: C57BL/6J, knock out (lacking interleukin [IL]-1 receptor, IL-1R(-/-)) and wild type mice underwent surgery of the tibia under general anesthesia. Separate cohorts of animals were tested for memory function with fear conditioning tests, or euthanized at different times to assess levels of systemic and hippocampal cytokines and microglial activation; the effects of interventions, designed to interrupt inflammation (specifically and nonspecifically), were also assessed. RESULTS: Surgery caused hippocampal-dependent memory impairment that was associated with increased plasma cytokines, as well as reactive microgliosis and IL-1beta transcription and expression in the hippocampus. Nonspecific attenuation of innate immunity with minocycline prevented surgery-induced changes. Functional inhibition of IL-1beta, both in mice pretreated with IL-1 receptor antagonist and in IL-1R(-/-) mice, mitigated the neuroinflammatory effects of surgery and memory dysfunction. INTERPRETATION: A peripheral surgery-induced innate immune response triggers an IL-1beta-mediated inflammatory process in the hippocampus that underlies memory impairment. This may represent a viable target to interrupt the pathogenesis of postoperative cognitive dysfunction.

Xenon pretreatment attenuates anesthetic-induced apoptosis in the developing brain in comparison with nitrous oxide and hypoxia.

BACKGROUND: Administration of certain general anesthetics to rodents during the synaptogenic phase of neurodevelopment produces neuronal injury. Preconditioning (pretreatment) can reduce tissue injury caused by a severe insult; the authors investigated whether pretreatment strategies can protect the developing brain from anesthetic-induced neurotoxicity. METHODS: Seven-day-old Sprague-Dawley rats were pretreated with one of the following: 70% xenon, 70% nitrous oxide, or 8% hypoxia for 2 h; 24 h later, rats were exposed to the neurotoxic combination of 70% nitrous oxide and 0.75% isoflurane for 6 h. Cortical and hippocampal neuroapoptosis was assessed using caspase-3 immunostaining. Separate cohorts were maintained for 40 days at which time cognitive function with trace fear conditioning was performed. In other pretreated cohorts, rat cortices were isolated for immunoblotting of caspase-3, Bcl-2, cytochrome C, P53, and mitogen-activated protein kinases. To obviate physiologic influences, organotypic hippocampal slices harvested from postnatal rat pups were cultured for 5 days and exposed to the same conditions as obtained for the in vivo studies, and caspase-3 immunostaining was again the measured outcome. RESULT: Xenon pretreatment prevented nitrous oxide- and isoflurane-induced neuroapoptosis (in vivo and in vitro) and cognitive deterioration (in vivo). Contrastingly, nitrous oxide- and isoflurane-induced neuroapoptosis was exacerbated by hypoxic pretreatment. Nitrous oxide pretreatment had no effect. Xenon pretreatment increased Bcl-2 expression and decreased both cytochrome C release and P53 expression; conversely, the opposite was evident after hypoxic pretreatment. CONCLUSIONS: Although xenon pretreatment protects against nitrous oxide- and isoflurane-induced neuroapoptosis, hypoxic pretreatment exacerbates anesthetic-induced neonatal neurodegeneration.

The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction.

INTRODUCTION: The impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide (LPS) challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 (HMGB-1), microglial activation, and cognitive dysfunction. Disabling the interleukin (IL)-1 signaling pathway is sufficient to reduce inflammation and ameliorate the disability. METHODS: Endotoxemia was induced in wild-type and IL-1R-/- mice by intra peritoneal injection of E. Coli LPS (1 mg/kg). Markers of inflammation were assessed both peripherally and centrally, and correlated to behavioral outcome using trace fear conditioning. RESULTS: Increase in plasma tumor necrosis factor-alpha (TNFalpha) peaked at 30 minutes after LPS challenge. Up-regulation of IL-1beta, IL-6 and HMGB-1 was more persistent, with detectable levels up to day three. A 15-fold increase in IL-6 and a 6.5-fold increase in IL-1beta mRNA at 6 hours post intervention (P < 0.001 respectively) was found in the hippocampus. Reactive microgliosis was observed both at days one and three, and was associated with elevated HMGB-1 and impaired memory retention (P < 0.005). Preemptive administration of IL-1 receptor antagonist (IL-1Ra) significantly reduced plasma cytokines and hippocampal microgliosis and ameliorated cognitive dysfunction without affecting HMGB-1 levels. Similar results were observed in LPS-challenged mice lacking the IL-1 receptor to those seen in LPS-challenged wild type mice treated with IL-1Ra. CONCLUSIONS: These data suggest that by blocking IL-1 signaling, the inflammatory cascade to LPS is attenuated, thereby reducing microglial activation and preventing the behavioral abnormality.

Role of transient receptor potential and acid-sensing ion channels in peripheral inflammatory pain.

Pain originating in inflammation is the most common pathologic pain condition encountered by the anesthesiologist whether in the context of surgery, its aftermath, or in the practice of pain medicine. Inflammatory agents, released as components of the body's response to peripheral tissue damage or disease, are now known to be collectively capable of activating transient receptor potential vanilloid type 1, transient receptor potential vanilloid type 4, transient receptor potential ankyrin type 1, and acid-sensing ion channels, whereas individual agents may activate only certain of these ion channels. These ionotropic receptors serve many physiologic functions-as, indeed, do many of the inflammagens released in the inflammatory process. Here, we introduce the reader to the role of these ionotropic receptors in mediating peripheral pain in response to inflammation.