Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-γ (PI3Kγ)

Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3Kγ, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3Kγ in sensory transmission, such as pain and itch has not been examined. In this study, we present the evidence for the first time, that genetic deletion of PI3Kγ enhanced scratching behaviours in histamine-dependent and protease-activated receptor 2 (PAR-2)-dependent itch. In contrast, PI3Kγ-deficient mice did not exhibit enhanced scratching in chloroquine-induced itch, suggesting that PI3Kγ selectively contributes to certain types of behavioal itch response. Furthermore, PI3Kγ-deficient mice exhibited normal acute nociceptive responses to thermal and mechanical noxious stimuli. Behavioral licking responses to intraplantar injections of formalin and mechanical allodynia in a chronic inflammatory pain model (CFA) were also not affected by PI3Kγ gene deletion. Our findings indicate that PI3Kγ selectively contributes to behavioral itching induced by histamine and PAR-2 agonist, but not chloroquine agonist

The INCLUDE study: INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community; identifying multimorbidity: Protocol for a pilot randomized controlled trial.

Background: Patients with inflammatory rheumatic conditions such as rheumatoid arthritis, polymyalgia rheumatica and ankylosing spondylitis are at increased risk of common comorbidities such as cardiovascular disease, osteoporosis and anxiety and depression which lead to increased morbidity and mortality. These associated morbidities are often un-recognized and under-treated. While patients with other long-term conditions such as diabetes are invited for routine reviews in primary care, which may include identification and management of co-morbidities, at present this does not occur for patients with inflammatory conditions, and thus, opportunities to diagnose and optimally manage these comorbidities are missed. Objective: To evaluate the feasibility and acceptability of a nurse-led integrated care review (the INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community (INCLUDE) review) for people with inflammatory rheumatological conditions in primary care. Design: A pilot cluster randomized controlled trial will be undertaken to test the feasibility and acceptability of a nurse-led integrated primary care review for identification, assessment and initial management of common comorbidities including cardiovascular disease, osteoporosis and anxiety and depression. A process evaluation will be undertaken using a mixed methods approach including participant self-reported questionnaires, a medical record review, an INCLUDE EMIS template, intervention fidelity checking using audio-recordings of the INCLUDE review consultation and qualitative interviews with patient participants, study nurses and study general practitioners (GPs). Discussion: Success of the pilot study will be measured against the engagement, recruitment and study retention rates of both general practices and participants. Acceptability of the INCLUDE review to patients and practitioners and treatment fidelity will be explored using a parallel process evaluation. Trial Registration: ISRCTN12765345

Transmitters and Pathways Mediating Inhibition of Spinal Itch-Signaling Neurons by Scratching and Other Counterstimuli

Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABAA and GABAB antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished) by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli

Effects of workplace-based dietary and/or physical activity interventions for weight management targeting healthcare professionals : a systematic review of randomised controlled trials

BACKGROUND: The prevalence of overweight and obesity is high amongst healthcare professionals and there is growing interest in delivering weight loss interventions in the workplace. We conducted a systematic review to (i) examine the effectiveness of workplace-based diet and/or physical activity interventions aimed at healthcare professionals and to (ii) identify and describe key components of effective interventions. Seven electronic databases were systematically searched. RESULTS: Thirteen randomised controlled trials met the inclusion criteria, of which seven had data available for meta-analysis. Where meta-analysis was possible, studies were grouped according to length of follow-up (<12 months and ≥12 months) and behavioural target (diet only, physical activity only or diet and physical activity), with outcome data pooled using a weighted random effects model. Nine studies reported statistically significant (between-group) differences. Four studies reported being informed by a behaviour change theory. Meta-analysis of all trials reporting weight data demonstrated healthcare professionals allocated to dietary and physical activity interventions lost significantly more body weight (-3.95 Kg, [95% CI -4.96 to- 2.95 Kg]) than controls up to 12 months follow up. CONCLUSIONS: Workplace diet and/or physical activity interventions targeting healthcare professionals are limited in number and are heterogeneous. To improve the evidence base, we recommend additional evaluations of theory-based interventions and adequate reporting of intervention content.Peer reviewedFinal Published versio