A5046913543- Neuroscience of respiration and sleep
- Heart Rate Variability and Autonomic Control
- Pain Mechanisms and Treatments
- Infection Control and Ventilation
- Neuroendocrine regulation and behavior
- Neuroscience and Neuropharmacology Research
- Cardiovascular Syncope and Autonomic Disorders
- Anesthesia and Pain Management
- Urinary Bladder and Prostate Research
- Anesthesia and Sedative Agents
- Circadian rhythm and melatonin
- Musculoskeletal pain and rehabilitation
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- COVID-19 and healthcare impacts
- Pain Management and Opioid Use
- Anesthesia and Neurotoxicity Research
- Cardiac, Anesthesia and Surgical Outcomes
- Pain Management and Placebo Effect
- Sleep and Wakefulness Research
- Pediatric Pain Management Techniques
- Inhalation and Respiratory Drug Delivery
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Opioid Use Disorder Treatment
University of Bristol
2016-2025
University Hospitals Bristol NHS Foundation Trust
2014-2024
University Hospitals Bristol and Weston NHS Foundation Trust
2023
Bristol Royal Infirmary
2002-2021
At Bristol
2020-2021
Bristol Royal Hospital for Children
2002-2020
Bristol Hospital
2020
North Bristol NHS Trust
2016-2020
University of Cincinnati Medical Center
2020
Erasmus MC - Sophia Children’s Hospital
2020
The locus coeruleus (LC) projects throughout the brain and spinal cord is major source of central noradrenaline. It remains unclear whether LC acts functionally as a single global effector or discrete modules. Specifically, while spinal-projections from neurons can exert analgesic actions, it not known they act independently ascending projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in with (LC:SC) prefrontal cortex (LC:PFC)...
A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that locus coeruleus (LC) norepinephrine (NE) activity during mediates unresponsiveness, and its action promotes awakenings. tested this using electrophysiological, behavioral, pharmacological, optogenetic techniques alongside auditory stimulation in freely behaving rats. found systemic reduction NE signaling lowered probability...
The potential aerosolised transmission of severe acute respiratory syndrome coronavirus-2 is global concern. Airborne precaution personal protective equipment and preventative measures are universally mandated for medical procedures deemed to be aerosol generating. implementation these having a huge impact on healthcare provision. There currently lack quantitative evidence the number size airborne particles produced during aerosol-generating inform risk assessments. To address this gap, we...
Chronic intermittent hypoxia (CIH) in rats produces changes the central regulation of cardiovascular and respiratory systems by unknown mechanisms. We hypothesized that CIH (6% O(2) for 40 s, every 9 min, 8 h day(-1)) 10 days alters modulation sympathetic activity. After CIH, awake (n = 14) exhibited higher levels mean arterial pressure than controls (101 +/- 3 versus 89 mmHg, n 15, P < 0.01). Recordings phrenic, thoracic sympathetic, cervical vagus abdominal nerves were performed situ...
Sympathetic nerve activity (SNA) is elevated in established hypertension. We tested the hypothesis that SNA neonate and juvenile spontaneously hypertensive (SH) rats prior to development of hypertension, this may be due augmented respiratory-sympathetic coupling. Using working heart-brainstem preparation, perfusion pressure, phrenic thoracic (T8) were recorded male SH normotensive Wistar-Kyoto (WKY) at three ages: neonates (postnatal day 9-16), 3 weeks old 5 old. Perfusion pressure was...
Pontospinal noradrenergic neurons are thought to form part of a descending endogenous analgesic system that exerts inhibitory influences on spinal nociception. Using optogenetic targeting, we tested the hypothesis excitation locus ceruleus (LC) is antinociceptive. We transduced rat LC by direct injection lentiviral vector expressing channelrhodopsin2 under control PRS promoter. Subsequent optoactivation evoked repeatable, robust, antinociceptive (+4.7°C ± 1.0, p < 0.0001) or...
The locus coeruleus (LC) in the pons is major source of noradrenaline (NA) brain. Two modes LC firing have been associated with distinct cognitive states: changes tonic rates are correlated global levels arousal and behavioural flexibility, whilst phasic responses evoked by salient stimuli. Here, we unify these two modelling response as a correlate prediction error when inferring states for action planning under Active Inference (AI). We simulate classic Go/No-go reward learning task...
Noradrenergic neurons of the brainstem extend projections throughout neuraxis to modulate a wide range processes including attention, arousal, autonomic control and sensory processing. A spinal projection from locus coeruleus (LC) is thought regulate nociceptive To characterize selectively manipulate pontospinal noradrenergic in rats, we implemented retrograde targeting strategy using canine adenoviral vector express channelrhodopsin2 (CAV2-PRS-ChR2-mCherry). LC microinjection...
Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. Respiratory-linked fluctuations in cardiac give rise to respiratory sinus arryhthmia (RSA), with maximum the post-inspiratory phase respiration. In present study, we investigated whether modulation intrinsically linked control using unanaesthetized working heart-brainstem preparation rat. Abolition post-inspiration, achieved by inhibition pontine Kolliker-Fuse nucleus, removed peaks efferent...
Background Most common anesthetic agents have been implicated in causing neurodegeneration the developing animal brain, leading to warnings regarding their use children. The hypothesis of this study was that exposure general anesthesia and surgery before 4 yr would associate with adverse neurodevelopmental outcomes at age 7 16 yr. Methods This cohort comprised 13,433 children enrolled Avon Longitudinal Study Parents Children, a prospective, population-based birth born between 1991 1993...
It is now generally accepted that SARS-CoV-2 can be spread by aerosols as well larger droplets from the upper respiratory tract, although relative importance of aerosol transmission remains incompletely answered.1Pöhlker ML Krüger OO Förster J-D et al.Respiratory and in infectious diseases.arXiv. 2021; (published online 1 March.)http://arxiv.org/abs/2103.01188Google Scholar Despite this, current UK infection control guidance for hospitals centred on premise are only generated specific...
Pain perception is decreased by shifting attentional focus away from a threatening event. This analgesia engages parallel descending control pathways anterior cingulate (ACC) to locus coeruleus, and ACC periaqueductal grey (PAG) - rostral ventromedial medulla (RVM), indicating possible roles for noradrenergic or opioidergic neuromodulators. To determine which pathway modulates nociceptive activity in humans, we used simultaneous whole brain-spinal cord pharmacological-fMRI (N = 39) across...
Abstract Background and Aims Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin–angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS to minimise hypotension, or continuing avoid hypertension, reduces injury remains unclear. Methods From 31 July 2017 1 October 2021, aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned...
The voltage-gated sodium channel NaV1.7, encoded by the SCN9A gene, is integral to nociceptor excitability and pain sensation. Multiple gain-of-function variants have been reported cause autosomal dominant painful channelopathies, including primary erythromelalgia paroxysmal extreme disorder, they linked pathogenesis of small fibre neuropathies. prevalence impact on carriers these NaV1.7 in wider population has yet be explored. A literature search was performed identify pathogenic...
α2-Adrenoceptors are widely distributed throughout the central nervous system (CNS) and systemic administration of α2-agonists such as dexmedetomidine produces clinically useful, centrally mediated sedation analgesia; however, these same actions also limit utility agents (ie, unwanted sedative actions). Despite a wealth data on cellular synaptic in vitro, it is not known which neuronal circuits modulated vivo to produce analgesic effect. To address this issue, we made recordings membrane...
Abstract The TRPA1 channel has been proposed to be a molecular transducer of cold and inflammatory nociceptive signals. It is expressed on subset small primary afferent neurons both in the peripheral terminals, where it serves as sensor, central nerve endings dorsal horn. substantia gelatinosa (SG) spinal cord key site for integration noxious inputs. SG are morphologically functionally heterogeneous precise synaptic circuits poorly understood. We examined how activation channels affects...
Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology descending control during development a pain phenotype rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at time injury allowing administration selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon expression allodynia...
Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in treatment severe refractory neuropathic pain. We tested hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb or Anaesthesia Dolorosa (n=5)) who obtained long-lasting benefit from were recruited. [11C]DPN and [15O]water PET scanning was performed consecutive sessions; first...
Abstract A role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated regulating energy homeostasis. The nucleus of the solitary tract (NTS), within brainstem dorsal vagal complex (DVC), integrates afferent information from viscera and plays a food intake. We hypothesized that astrocytes this respond to, influence, Mice fed high‐fat chow 12 hr during dark phase showed NTS activation, reflected an increase number...