BJA/RCoA Project Grant
The successful applicants for the BJA / RCoA Project Grant were:
Principal Applicant
Dr A Rice
Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London.
Title of Project
Elucidation of the spino-amygdaloid pathways which drive neuropathic and arthritic pain-related anxiety.
Amount
£50,000
Abstract
Psychological co-morbidities are prevalent in the chronic pain associated with neuropathy and arthritis, and are significant complicating factors in clinical management. We have been successful in modelling the important co-morbidity of anxiety in animal models of persistent pain and now wish to elucidate its underlying neurobiology. This project focuses on the role of the spinal nociceptive input to the amygdala in driving neuropathic and arthritic pain-related anxiety. We will study this in rat models of traumatic and varicella zoster associated neuropathic pain and of osteoarthritis. To do this we will selectively ablate, using saporin based technologies, the two major spinal nociceptive pathways projecting to the amygdala in order to elucidate their relative importance. Selective stimulation studies will be performed to confirm ablation findings. Outcome measures will be anxiety-like behaviour in open field and elevated plus maze paradigms. Finally, we will perform pilot studies examining depression-like behaviour in these animal models.
Final Report from Prof A Rice (1.18 MB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Professor J Hall
School of Medicine, Department of Anaesthetics and Intensive Care Medicine, Cardiff University.
Title of Project
Imaging neural responses to pain related stimuli in patients with chronic non-malignant pain (CNMP) pre and post a pain management programme.
Amount
£50,000
Abstract
Chronic non-malignant pain (CNMP) can pose a major clinical, social and economic problem; improving the understanding and management of CNMP needs to be high on the research agenda. Obtaining reliable objective information related to the individual's subjective pain experience provides a powerful means of understanding CNMP and its management. The aims of the study are to:
- Investigate the neural correlates of changes in attentional processes and emotional responses to pain related stimuli in patients with CNMP.
- Assess whether there is a correspondence between neural activity and standardized self report measures of catastrophising, fear/anxiety and disability.
- Establish whether brain structure and neural activation in response to pain related stimuli changes following a multidisciplinary pain management programme.
The majority of neuroimaging carried out to date has focused on acute experimentally induced pain, which can be very different from CNMP in its characteristics and threat value, hence the importance of this study.
First Year Progress Report from Prof J Hall (36 KB)
Second Year Progress Report from Prof J Hall (318 KB)
Final Report from Prof J Hall (811 KB)
Principal Applicant
Dr I Nagy
Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London.
Title of Project
The role of N-arachidonoyl phosphatidylethanolamine phospholipase D in regulating the activity of primary sensory neurons in naive and inflammatory conditions.
Amount
£49,867
Abstract
Intractable pain of various origins, including inflammation of peripheral tissues, is a major cause of long-term physical and emotional suffering and the lack of well-being, which necessitates the development of new analgesics. Here, we propose to study the role of the anandamide-synthesising enzyme, N-arachidonoyl phosphatidylethanolamine phospholipase D (NAPE-PLD), in the development of inflammation-evoked increased responsiveness of primary sensory neurons (PSN), which underlies the development of inflammatory pain. Using combined immunohistochemistry we will study the expression pattern of NAPE-PLD in dorsal root ganglia (DRG). We will also study inflammation-induced changes in that pattern by using immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction. Finally, we will study the effect of small interference RNA-induced downregulation of NAPE-PLD expression on spontaneous, and mild noxious mechanical-, and thermal, stimulation-evoked expression of phosphorylated extracellular signal-regulated protein kinase 1/2, which is a surrogate marker of noxious stimulus-evoked activation of PSN, in inflammatory conditions.
First Year Progress Report from Dr I Nagy (810 KB)
Final Report from Dr I Nagy (1.93 MB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Professor N Webster
Academic Unit of Anaesthesia and Intensive Care, University of Aberdeen.
Title of Project
Polymorphisms of SP-A and SP-D in patients with ventilator associated pneumonia.
Amount
£30,119
Abstract
Surfactant protein (SP) -A and SP-D may have a role in the development and outcome from ventilator associated pneumonia (VAP) in the critically ill due to the effects of these proteins on the immune system and clearance of bacteria from the lung. Polymorphisms in the SP-A and SP-D genes may influence expression and or function of SP-A/SP-D mRNA and/or proteins and hence development, disease progression and/or outcome from VAP. We therefore propose to determine the allele frequency of selected polymorphisms in SP-A and SP-D genes in critically ill patients with and without VAP. Our hypothesis is that a specific genotype or haplotype will be associated with development, progression or outcome of VAP.
2009 Progress Report from Prof N Webster (32 KB)
2012 RSM Abstract from Prof N Webster (43 KB)
December 2012 Progress Report from Prof Webster (34 KB)
2014 Final report from Prof N Webster (97 KB)
Principal Applicant
Dr R Ni Mhuircheartaigh
Nuffield Dept of Anaesthetics/FMRIB, University of Oxford.
Title of Project
The 'thalamocortical switch' and consciousness: Is interruption of thalamocortical transmission the cause or a consequence of induction of general anaesthesia by Propofol.
Amount
£49,955
Abstract
We propose a collaborative project between investigators with experience in Anaesthesia, Neuroimaging, Physics and Data Analysis to study electroencephalographic (EEG) and functional magnetic resonance imaging (FMRI) findings at increasing levels of propofol anaesthesia and sedation. We will administer propofol to human volunteers and gather simultaneous EEG and FMRI signals at rest and during acoustic and noxious laser stimulation. A target controlled infusion will be used to record data awake and at 1, 2 and 3 mcg ml-1 of Propofol. This data will be used in the first instance to correlate changes in EEG parameters (power spectra, laser evoked potential amplitude and latency) and FMRI responses at each targeted propofol level. This will be used to define depth of sedation by physiological findings rather than pharmacological targets thus identifying appropriate epochs for within subject-between states analysis of differences in effective connectivity between regions of the brain across awake, sedated and deeply sedated states.
First Year Progress Report from Dr N Mhuircheartaigh (35 KB)
Summary Final Report from Dr R Mhuircheartaigh (108 KB)
Principal Applicant
Dr I Moppett
University Department of Anaesthesia, Queens Medical Centre, Nottingham.
Title of Project
Computational modelling of the cerebrovascular behaviour of patients undergoing carotid endarterectomy.
Amount
This is a joint funded project. £38,168 (£10,000 from AAGBI giving total grant of £48,168).
Abstract
Aims
To develop a credible computational model of cerebrovascular behaviour in patients undergoing carotid endarterectomy to provide hypothesis testing and behaviour prediction for future research and clinical management in this high risk patient group.
Methodology
We will refine an existing, validated model of the cerebral circulation using individual patient level data collected in a prospective study by one of the investigators (SH) and published data.
The model will be developed using control systems engineering techniques in several parallel streams: model tuning, validation and robustness analysis; incorporation of baroreflex sensitivity variation; development of effects of vasoactive drugs; initial behaviour prediction testing. A virtual population of experimental subjects will be created who correspond to clinically identifiable subset of the carotid endarterectomy population.
Main Outcome
A credible, validated population of virtual subjects to be used to investigate peri-operative cerebrovascular behaviour.
Final report from Dr I Moppett (55 KB)
