The clinical translational research focus of the CTPR via the integration of basic and multidisciplinary clinical research is organised under five main research themes

Pain Classification and Clinical Pain Phenotyping

Dr Catherine Doody

Research is focussed on the identification and classification of Musculoskeletal related pain states according to underlying neurophysiological pain mechanisms. The effects of Physiotherapy and other multidisciplinary interventions are investigated using quantitative sensory testing, clinical testing and patient reported outcome measures.

View Dr Catherine Doody's Research Publications

Pain Management-Rehabilitation and Intervention

Dr Brona Fullen

Collaborations between physiotherapists, occupational therapists, anaesthetists and psychologists to investigate the impact of rehabilitation strategies (cognitive behavioural therapy and acceptance and commitment therapy programmes) on function, mood, sleep and quality of life in people with chronic pain, diabetic neuropathy and spinal cord injuries using questionnaires and objective testing.

View Dr Brona Fullen's Research Publications

Chronic pain is common after spinal cord injury (SCI) and dedicated SCI cognitive behavioural therapy pain management programmes (CBT-PMPs) are being used more frequently in clinical settings. Developing internet-delivered treatment options may overcome barriers to the access and uptake of centre-based programmes. This study examined the impact of an internet-delivered CBT-PMP on quality of lie (QoL), pain, mood and sleep. Adults with SCI pain (>3 months) were recruited and randomly assigned to the intervention or control group. The intervention comprised a six module CBT-PMP delivered once weekly.

Thirty-five participants were recruited to the intervention and 34 to the Control group. At 3 months the drop-out rate was 26%. On average, participants accessed three (SD 2.1) of six modules. No difference in QoL was found, although differences were found for current and worst pain ratings and Brief Pain Inventory (interference) sub-scale. Almost half (48%) of the intervention group rated themselves improved or very much improved.This approach demonstrates the potential of an internet-delivered SCI specific CBT-PMP in reporting significant statistical and clinical benefit in pain intensity and interference. Strategies to improve engagement are needed.

Musculoskeletal (MSK) pain is a common issue in people who are obese. Multidisciplinary weight management services (WMS) are effective in reducing weight; however, MSK pain as an outcome is not routinely reported. This study sought to establish the prevalence of MSK pain and the impact of a WMS on pain. Data from a national WMS was examined to establish changes in anthropometric and pain prevalence and intensity scores as well as establishing variables predictive of achieving clinically significant changes (CSC) in pain scores.

Over half of the 806 patients attended their reassessment at 6 months (59%, n = 476). At baseline 70% reported low back pain (LBP) and 59% had knee pain. At reassessment 37.3% of patients lost ≥5% body weight, 58.7% were weight stable (5% weight loss or gain) and 4.0% gained ≥5% body weight. Low back and knee pain prevalence reduced significantly for those who lost ≥5% body weight. Variables predictive of a CSC in LBP numerical rating scale (NRS) score included a higher baseline NRS score, weighing more, and rating losing weight as being important (p < 0.05). Higher baseline NRS and being younger resulted in higher odds of a CSC in knee pain NRS (p < 0.05).

Weight loss can reduce MSK pain, particularly for those who lose more weight. Including pain management strategies within WMS may provide a more holistic approach to obesity management.

Stratifying people with low back pain (LBP) has been shown to demonstrate improved outcomes as well as being cost effective. This study aimed to examine this approach using group-based stratified care in Primary care. Patients recruited from 60 Primary Care practices were recruited and stratified using the Startback tool and offered risk-matched group care. Outcomes included functional disability, pain, psychological distress and beliefs. The stratified care group were compared with a historical generic group intervention.

Overall 251 patients were recruited in the stratified care group and 332 in the historical care group. At 12 weeks post programme those in the high-risk stratified group demonstrated better outcome over the controls, those in the medium-risk stratified group did equally well and even though the low risk group had less treatment they did as well as the historical group. Incorporating this model into Primary care provides an early and effective management for those with LBP.

Health literacy (HL) is a person’s ability to seek, understand and implement health-related information, which is particularly important for those with chronic disease. This study aimed to establish if health literacy is linked to poorer outcomes and behaviours in people with chronic pain. New patients attending one of three university teaching hospital out-patient pain services were recruited and completed questionnaires relating to demographics, HL, quality of life, beliefs And disease-related knowledge. Of the 131 people recruited more than half (54%) had inadequate HL. Following multivariate analysis disease-related knowledge and beliefs about ability to control their pain were independently associated with their HL status. Overall, low HL is prevalent in those with chronic pain and may impact on their ability to independently self-manage their condition.

Pain Measurement and Outcome Assessment

Dr Catherine Blake

Assessment of the multidimensional nature of pain is required for descriptive, discriminative, prognostic and evaluative purposes. This underpins the ability to measure change and evaluate intervention efficacy. Collaboration between clinicians and statisticians to test and develop robust measurement protocols, determine clinically important change and develop algorithms to identify predictors and prognostic indicators for treatment outcome in people of all ages.

View Dr Catherine Blake's Research Publications

Basic Science Pain Research

Professor Gerry Wilson

Personalised medicine will be promoted through the use of biomarker profiling with patient stratification and therapeutic targeting to maximise health and minimise disability. Research into the genetic basis of musculoskeletal diseases (rheumatoid arthritis and osteoarthritis), discovery of biomarkers predictive of disease outcome, pharmacogenetics of anti-rheumatic therapies and epigenetic regulation of inflammatory cytokines

View Professor Gerry Wilson's Research Publications

The immune system is often looked upon as a response to infection. While it has this function, it also does so much more, including being crucial for the normal growth and replenishment of the cells in the body. We looked at a type of immune cell, called a macrophage, that has a role in the inflammation stage but also in the growth and healing phase. These cells are like conductors of an orchestra: they tell the other immune cells when to fight infection but also when to turn off “fight” mode and to turn on “healing” mode. Therefore, when they stop working properly, the whole immune system can go out of tune.

This happens in many auto-immune diseases, including rheumatoid arthritis. We previously found a difference in the DNA of people living with rheumatoid arthritis compared to those without it. We showed that people with this difference made less of a protein then called C5orf30 in their macrophages (those conductors of the immune system). As a result of this research, the protein was given the official name MACIR (MACrophage Iimmunometabolism Regulator).

Rheumatoid arthritis (RA) is a widespread chronic disease affecting about 45,000 people in Ireland.  Without proper treatment, it is associated with disability and lower life expectancy. Organizations such as Arthritis Ireland and the Health Service Executive offer self-management education programmes, yet many people choose not to take part in these kinds of programmes.  This study will help us to understand why, how these people currently self-manage their condition and what can be done to better support them.

This study uses photography to capture people’s experience of living with RA.  Participants will receive cameras and training from a photographer.  They will be asked to take photos of their experiences of living with the condition.  They will discuss their photos with the researcher and share their perspectives and insight as a group. Several exhibitions of the images have been organized so that participants - if they wish - can “voice” their experience of self-manging RA with a wider community.  Findings of the study will be presented to relevant people who influence the care of people with RA (such as researchers, healthcare practitioners or technical experts).  Together we will discuss the needs of the community and how to develop better solutions to support people with RA in the future.

Rheumatoid Arthritis (RA) varies from a mild to a severe, unremitting illness characterized by uncontrolled inflammation with consequent damage to cartilage and bone of joints. It is now known that our DNA determines the likelihood of severity of disease. The study of patients DNA can then facilitate personalized approach where patients likely to develop severe disease will receive more aggressive treatment compared to the patients with mild disease.

My project will identify genetic variants associated with severity of RA which will help us to establish a risk prediction score for early identification and stratification of patients. The results obtained during this study will also assist the clinicians in determining the optimal treatment to be given to patients, more quickly and efficiently. 

Down syndrome is a chromosomal disorder caused by full Trisomy 21 (95%), Robertsonian Translocation or Mosaicism. Approximately 110 babies with Down syndrome are born in Ireland each year, making Ireland’s birth rate of children with Down syndrome the highest in Europe. This puts Irish researchers in a unique position to engage in robust research into conditions that affect children with Down syndrome.

A variety of medical conditions and immunological abnormalities are associated with Down syndrome. Immune dysregulation predisposes children with Down syndrome to high frequencies of haematologic malignancies, increased susceptibility to infections, and, most remarkably, a high incidence of autoimmune diseases, including arthritis. DA is an inflammatory joint condition affecting children with Down syndrome. The NCPR at OLCHC provides care to 40 children with DA, the largest reported cohort worldwide. Our research has demonstrated that the prevalence of DA is 18-21 times greater than Juvenile Idiopathic Arthritis (JIA) (JIA prevalence 1/1000)

Chronic nonbacterial osteomyelitis (CNO) is a serious, rare auto-inflammatory disease.  The cause of CNO is not known.  Some patients’ CNO is worse than others’.  We want to know why.  We will use state-of-the-art technology to look at patients’ genes.  We will see if there’s an association between certain genes, certain bone biopsy findings and how bad the CNO is. This might help us figure out why CNO happens.  Then we might be able to treat it more effectively. We think that slight differences in genes might help explain why CNO happens because some patients with CNO have a brother or sister or parent with CNO.  In CNO, bones get inflamed without a good reason.  This can make them painful, swollen and hard to use.

Some patients don’t have swelling that we can see which makes it hard to diagnose.  Patients have scans done to help us to diagnose CNO.  We often need to take a sample or biopsy of the bone to make sure it is not cancer or infection. CNO is treated by paediatric rheumatologists.  If we don’t treat CNO, it can lead to poor growth or fracture

Auto-inflammatory conditions commonly cause patients to have episodes of unprovoked inflammation that can affect one or multiple organs in the body. These conditions can be caused by a mutation (change) in a gene (part of their DNA) that controls what is called the innate immune system.  The innate immune system manages the body’s rapid response to threats; it acts as the first responder to an infection caused by pathogens; pathogens are germs that can cause disease, such as viruses and bacteria. In response to a pathogen, inflammatory signals are released in the infected area which prepares the body to fight the infection. In patients with an auto-inflammatory condition, the body acts as if an infection were present, even when there is none.

Although many of these auto-inflammatory conditions are very severe, they are often very responsive to new anti-inflammatory medicines. These medicines work by blocking the chemical signals that trigger inflammation in our bodies. Identifying the genetic cause (i.e. mutations in patient DNA) of these conditions can help doctors choose the best treatment for patients.  Behçet’s Disease (BD) is an auto-inflammatory condition where patients’ symptoms include ulcers in the mouth or genitals, inflammation in the eye, rashes and, less commonly, inflammation of the bowels, large blood vessels and the brain. It is believed to be caused by a combination of a large number of variations in the DNA sequence, each contributing small but accumulative biological effects, and unknown environmental exposure(s)

Psoriatic arthritis, a form of inflammatory arthritis that is associated with psoriasis, presents with heterogeneous clinical manifestations making it challenging to diagnose. A range of classification criteria has been developed but diagnosis relies heavily on the experience and expertise of the treating clinician. Furthermore, treatment is often selected on a “trial and error” basis with the patient cycling through various treatments in the hope that one will prove effective and safe. With no specific diagnostic test to discriminate psoriatic arthritis from other arthrophathies and unpredictable patient response to treatment it is accepted widely that there is an urgent and significant as yet unmet need for biomarkers for both.  Despite widespread excitement and expectation that ‘omics technologies will deliver novel multiplexed biomarkers to herald a new era of personalized medicine only a few such ‘omics-derived tests have reached clinical use.

Having established an excellent local clinical research capability and multi-disciplinary teams (including clinical investigators, biomedical researchers and statisticians) the we have undertaken focused proteomic biomarker discovery programmes and applied statistical algorithms to identify a panel of novel potential protein biomarkers for psoriatic arthritis. Notably to assemble this novel panel we have taken competitive advantage of excellent local clinical samples, a ‘quantitative proteomics’ mass spectrometry platform and access to a superb multiplex (Luminex) immunoassay facility.

Osteoarthritis (OA) is the most common form of joint disease globally and is associated with significant morbidity and disability. Increasing evidence points to an important inflammatory component in the development and progression of OA. The precise pathways involved in OA inflammatory processes remain to be clarified. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals can induce inflammation and arthritis and recent studies point to a potential pathogenic role in OA. This long-standing project seeks to explore the relationship and potential mechanistic pathways linking calcium-containing crystals and OA.

Evidence Based Medicine

Professor Laserina O’Connor

Collaborations between general practitioners, statisticians and physiotherapists to conduct systematic reviews and meta-analyses in order to interpret research evidence which informs our programmes of research, in addition to the wider interdisciplinary scientific community and clinical colleagues. Evidence based medicine will also be used to develop and implement national guidelines for acute and chronic non-cancer pain.

View Professor Laserina O’Connor's Research Publications