Effects of selective opiate antagonists on morphine-induced hyperalgesia in domestic fowl

Morphine typically produces analgesia in a variety of species by acting as an agonist at mu and perhaps delta opioid receptors. Recent research, however, has identified a biological model in which morphine produces a naloxone-reversible, paradoxical hyperalgesic response to a noxious thermal stimulus in young domestic fowl. The development of opiate receptor antagonists with selective activity at heterogeneous populations of opioid sites may be a useful tool to differentiate the action of an opiate at a particular receptor. In this study, the hyperalgesic actions of morphine (1.25 to 5.0 mg/kg im) on a standard hot-plate test were examined following administration (10 ug/5 ul icv) of the mu antagonist beta-funaltrexamine, the delta antagonist naltrindole, or the kappa antagonist nor-binaltorphamine in 15-day old White Leghorn cockerels. Morphine produced a dose-dependent decrease in mean jump latencies (i.e., hyperalgesia). Mu receptor antagonism attenuated morphine-induced hyperalgesia. Kappa receptor antagonism attenuated morphine-induced hyperalgesia only at the highest morphine dose (i.e., 5.0 mg/kg) and delta receptor antagonism failed to attenuate morphine-induced hyperalgesia. These results support the notion that atypical morphine-induced hyperalgesia, like morphine-induced analgesia, is mediated primarily by mu receptor activation

Do I sound anxious? Emotional arousal is linked to changes in vocalisations in domestic chicks (<em>Gallus gallus</em> dom.)

\ua9 2024A major goal in animal welfare science is the development of methods that quantify or ‘read-out’ current affective states in freely behaving animals. In mammalian models, changes in acoustic parameters within vocalisations have been linked to differences in emotional arousal, although there are very few studies showing changes in vocalisations that act as indicators of valence (positive or negative affect). Currently, there are very few studies on vocal indicators of emotion in birds. To determine the link between acoustic parameters within vocalisations and emotion in domestic chicks (Gallus gallus dom.), we used a well-validated paradigm that purports to elicit two distinct, negative emotional states: anxiety and depression. In this paradigm, chicks in social isolation initially show high rates of distress calls (anxiety-like phase: high arousal/negative affect) that decrease over the next 20–30 minutes to a depression-like phase (low arousal/negative affect). We analysed acoustic parameters of distress vocalisations from Legbar chicks (4–7 days old) that were placed in social isolation for 30 minutes, either with or without a mirror (Isolated: n=18; Mirror: n=16), (a mirror is known to reduce the negative behavioural and physiological indicators of isolation). Chicks in the Isolated condition produced louder calls, of a higher frequency, and calls were individually longer, and more ‘degraded’ (higher entropy and lower harmonics-to-noise ratio) compared to the Mirror condition. However, the call rate did not drop below 50 % of the initial rate in either condition, indicating the chicks in this study did not reach the criteria for the depression-like phase of the paradigm. To investigate further we analysed vocalisations at times during a trial when calls were at a high rate per minute (indicating a higher level of emotional arousal at that point in time) and we found those vocalisations were louder, more ‘degraded’, longer and higher in frequency across both conditions. These results are consistent with findings across several species of mammal, indicating that changes in emotional arousal in negatively valanced situations give rise to consistent changes in vocal parameters across a wide range of species. Indeed, further work could look to see if the same links are found in groups such as chelonians, crocodilians and geckos, as their vocal production mechanisms share some similarities. There could also be scope to use these changes to automatically detect shifts in emotion in captive animals

Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>Recent research has established correlations between stress, anxiety, insomnia and excess body weight and these correlations have significant implications for health. This study measured the effects of a proprietary blend of extracts of <it>Magnolia officinalis </it>and <it>Phellodendron amurense (</it>Relora^®) on anxiety, stress and sleep in healthy premenopausal women.</p> <p>Methods</p> <p>This randomized, parallel, placebo controlled clinical stud<b>y </b>was conducted with healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scores above the national mean for women on self-reporting anxiety. The intervention w<b>as </b>Relora (250 mg capsules) or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety. The study was conducted by Miami Research Associates, a clinical research organization in Miami, FL.</p> <p>Results</p> <p>The intent-to-treat population consisted of 40 subjects with 26 participants completing the study. There were no significant adverse events. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments conducted in this study including salivary cortisol and amylase levels, appetite, body morphology and sleep quality/latency were not significantly changed by Relora in comparison to placebo.</p> <p>Conclusion</p> <p>This pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.</p

Ventures

https://openspace.dmacc.edu/ventures/1000/thumbnail.jp

Omicron variant infection in inflammatory rheumatological conditions – outcomes from a COVID-19 naive population in Aotearoa New Zealand

Background: Due to geographic isolation and border controls Aotearoa New Zealand (AoNZ) attained high levels of population coronavirus disease-19 (COVID-19) vaccination before widespread transmission of COVID-19. We describe outcomes of SARS-CoV-2 infection (Omicron variant) in people with inflammatory rheumatic diseases in this unique setting. Methods: This observational study included people with inflammatory rheumatic disease and SARS-CoV-2 infection in AoNZ between 1 February and 30 April 2022. Data were collected via the Global Rheumatology Alliance Registry including demographic and rheumatic disease characteristics, and COVID-19 vaccination status and outcomes. Multivariable logistic regression was used to explore associations of demographic and clinical factors with COVID-19 hospitalisation and death. Findings: Of the 1599 cases included, 96% were from three hospitals that systematically identified people with inflammatory rheumatic disease and COVID-19. At time of COVID-19, 1513 cases (94.6%) had received at least two COVID-19 vaccinations. Hospitalisation occurred for 104 (6.5%) cases and 10 (0.6%) patients died. Lower frequency of hospitalisation was seen in cases who had received at least two vaccinations (5.9%), compared to the unvaccinated (20.6%) or those with a single vaccine dose (10.7%). In multivariable adjusted models, people with gout or connective tissue diseases (CTD) had increased risk of the combined outcome of hospitalisation/death, compared to people with inflammatory arthritis. Glucocorticoid and rituximab use were associated with increased rates of hospitalisation/death. All patients who died had three or more co-morbidities or were over 60 years old. Interpretation: In this cohort with inflammatory rheumatic diseases and high vaccination rates, severe outcomes from SARS-CoV-2 Omicron variant were relatively infrequent. The outcome of Omicron variant infection among vaccinated but SARS-CoV-2 infection-naive people with inflammatory rheumatic disease without other known risk factors were favourable. Funding: Financial support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) included management of COVID-19 Global Rheumatology Alliance funds

Clinically Relevant Behavioral Endpoints in a Recurrent Nitroglycerin Migraine Model in Rats

BACKGROUND: This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. METHODS: Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip. RESULTS: The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner. CONCLUSIONS: These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies

The impact of COVID-19 on rheumatology training—results from the COVID-19 Global Rheumatology Alliance trainee survey

Objective: The aim was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the clinical experiences, research opportunities and well-being of rheumatology trainees. / Methods: A voluntary, anonymous, Web-based survey was administered in English, Spanish or French from 19 August 2020 to 5 October 2020. Adult and paediatric rheumatology trainees were invited to participate via social media and email. Using multiple-choice questions and Likert scales, the perceptions of trainees regarding the impact of the COVID-19 pandemic on patient care and redeployment, learning and supervision, research and well-being were assessed. / Results: There were 302 respondents from 33 countries, with 83% in adult rheumatology training. An increase in non-rheumatology clinical work was reported by 45%, with 68% of these having been redeployed to COVID-19. Overall, trainees reported a negative impact on their learning opportunities during rheumatology training, including outpatient clinics (79%), inpatient consultations (59%), didactic teaching (55%), procedures (53%), teaching opportunities (52%) and ultrasonography (36%). Impacts on research experiences were reported by 46% of respondents, with 39% of these reporting that COVID-19 negatively affected their ability to continue their pre-pandemic research. Burnout and increases in stress were reported by 50% and 68%, respectively. Physical health was negatively impacted by training programme changes in 25% of respondents. / Conclusion: The COVID-19 pandemic has had a substantial impact on rheumatology training and trainee well-being. Our study highlights the extent of this impact on research opportunities and clinical care, which are highly relevant to future curriculum planning and the clinical learning environment

Neuroethics, Painience, and Neurocentric Criteria for the Moral Treatment of Animals

Neuroscience affords knowledge that can be leveraged in the ontological valuation of individuals, groups, and species. Sociocultural sentiments, norms, and mores may impede embracing such knowledge to revise moral attitudes, ethics, and policies. We argue that the practices of neuroethics will be valuable in that they ground ethico-legal discourse in (1) naturalistic philosophy; (2) the current epistemological capital of neuroscience; (3) the issues, problems, and solutions arising in and from neuroscientific research and its applications; and 4) the use of neurocentric criteria—such as painience—to define and resolve ethical decisions regarding attitudes toward and treatment of nonhuman animals