Though methotrexate is the first-line drug to be given for Juvenile idiopathic arthritis (JIA), it is only effective or tolerated in half of the children and young people who receive it.

Those patients not helped by the drug have to wait longer to receive second line therapies, potentially prolonging the severe joint pain and other symptoms which often have a devastating impact on children and their families.

The study, published in the journal eBioMedicine, could facilitate more precise research into the identification of response predictors to methotrexate, such as biomarkers, and lead to better forecasting of likely outcomes following drug initiation.

It confirms that one in eight children and young people starting methotrexate will demonstrate improvements in inflammatory features of disease yet have some symptoms.

They also showed that in 16 per cent of children taking methotrexate, improvements in disease activity could be slower than in others over time.

Lead author said: “Giving methotrexate to children who it will not help wastes time, money and effort for healthcare services-  as well as unnecessarily exposing them to potential side effects.

“But now machine learning has opened the door made it  possible to predicting which aspects of a child’s disease would be helped by the drug and so which children should start other therapies either alongside or instead of methotrexate straight away.

“In addition, this work shows how clinical trials are missing the mark in only looking at drug ‘response’ or ‘non-response’ for childhood-onset arthritis.

“This oversimplification could lead to a drug being labelled as ‘effective’ when key symptoms such as pain remain, or ‘ineffective’ where a significant improvement is seen in one aspect of this complex disease.”

The research is funded by the Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children’s Charity, Olivia’s Vision, and the National Institute for Health Research as part of the CLUSTER consortium.

The research team accessed data from four nationwide cohorts of children and young people who began their treatment before January 2018.

Juvenile arthritis disease activity score components (including how many swollen joints, a doctor’s perception of disease, a patient/parent report of wellbeing, results of a blood test for inflammation) were recorded at the start of treatment  and over the following year.

They used machine learning identify clusters of patients with distinct disease patterns following methotrexate treatment, predict clusters; and compare clusters to existing treatment response measures.

From 657 children and young people verified in 1241 patients they identified Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%).

Two other clusters they called Persistent physician global assessment (8%) and Persistent parental global assessment  (13%), were characterised by improvement in all activity score features except one.

Dr Shoop-Worrall added: “The longer-term impact of this slower disease control needs further investigation. Our study also demonstrates the utility of machine learning methods to uncover clusters of children as a basis for stratified treatment decisions.

“This work builds on existing studies of methotrexate treatment response, confirming that response is not bivariate but can be highly variable across different features of disease within individuals.

“At the moment trials of methotrexate in JIA categorise patients into responders and non-responders.

“That misclassification can compromise studies looking to identify predictors of response, such as biomarkers.”

• The paper Towards Stratified Treatment of JIA: Machine Learning Identifies Subtypes in Response to Methotrexate from Four UK Cohorts is available
• Image shows open bottle of methotrexate drug—one of the first chemotherapeutic drugs used in the early 1950s (released by the National Cancer Institute in the US,  part of the National Institutes of Health)

Osteoarthritis (OA) is the most common form of joint disease, affecting more than 250 million people worldwide and representing a major and growing cause of long-term disability. OA is a complex disorder where multiple factors such as obesity, joint injury and genetics contribute to structural deterioration, and potentially failure, of synovial joints. Despite a high burden of disease there are no approved disease-modifying OA drugs (DMOAD) and current strategies for pain relief are inadequate. Eventually many patients progress to late-stage OA and undergo joint replacement surgery with unsatisfactory outcomes in a significant proportion of cases.

The newly published study explored the role of the human TSG-6 protein in osteoarthritis (OA), and evaluated the disease modifying potential of Link_TSG6 (a fragment derived from the TSG-6 protein) in cell, rodent and human cartilage explant models of OA. Results from the study showed that Link_TSG6 suppresses the production of enzymes implicated in cartilage damage - a hallmark of OA. Furthermore, administration of Link_TSG6 reduced cartilage breakdown, underpinning its potential as a DMOAD, and also reduced touch-evoked pain behaviour supporting a possible analgesic effect.

Caroline Aylott, Head of Research Delivery at charity Versus Arthritis, who co-funded the research, said:

“There is a critical need for treatments that slow down the progression of osteoarthritis to delay or avoid joint replacement surgery and to reduce the pain that so many experience. The data is promising and whilst the research is in its early stages, it shows that Link_TSG6 has the potential to offer a new class of disease modifying drugs to treat osteoarthritis."

The study revealed that Link_TSG6 mimics the intrinsic anti-inflammatory and chondroprotective properties of the full-length TSG-6 protein, as well as having greater potency. In addition, it was found that a substantial proportion of cartilage explants from OA donors undergoing knee-replacement surgery were responsive to Link_TSG6 treatment suggesting that this protein biologic may have therapeutic utility for a large number of OA patients.

"This study has identified a potential new treatment for OA with disease modifying and analgesic properties," said Professor Tony Day, a co-corresponding author, from the Wellcome Centre for Cell-Matrix Research, University of Manchester, and Chief Scientific Officer of Link Biologics. “It is extremely rewarding to obtain such compelling preclinical data and we intend to progress this work by advancing Link_TSG6 towards human clinical trials over the next few years.”

The findings, published in the show people with rheumatic and musculoskeletal conditions are often prescribed opioids to manage their pain, and a proportion of them will become long term users with the associated risks of dependence and harmful side effects, point out the authors.

The study published today was funded by the National Institute for Health and Care Research (NIHR) and FOREUM. It was based on over 841,000 anonymised medical records in Clinical Practice Research Datalink (CPRD), a primary care research database representative of the national population.

Most research defines long term opioid use as 90 or more days, although definitions in the scientific literature vary, and there are no contemporary estimates of the scale of long-term opioid use, they add.

To assess the proportion of patients transitioning to long term use among those newly started on an opioid, they drew on the anonymised medical records of 841,047 adults.

Each patient had been newly prescribed an opioid up to 6 months before, or any time after, their diagnosis between January 2006 and end of October 2021 and had been followed up for at least a year.

Long term use was defined as either standard (3 or more opioid prescriptions issued within a 90-day period, or 90+ days’ opioid supply in the first year); or stringent (10 or more opioid prescriptions filled over more than 90 days, or 120+ days' opioid supply in the first year); or broad (more than 3 opioid prescriptions at monthly intervals in the first 12 months).

In all, 1,081,216 new episodes of opioid use were identified among all the patients, just under 17% of whom transitioned to long term use under the standard, 11% under the stringent, and 22% under the broad definitions. 

The highest proportion of long-term opioid users were patients with fibromyalgia—27.5% 21%, and 34% for each of the respective definitions—followed by those with rheumatoid arthritis—26%, 18.5%, and 32%---and those with axial spondyloarthritis—24%, 17%, and 30%. 

The proportion of patients with SLE and fibromyalgia who transitioned noticeably increased between 2006 and 2019. In fibromyalgia patients this was 22% to 33%---reaching 29% in 2020.

A statistically significant decreasing trend was observed for patients with rheumatoid arthritis, although the overall proportion remained high at 24.5% in 2020.

Under the stringent definition, 1 in 5 patients with fibromyalgia and 1 in 6 of those with rheumatoid arthritis or axial spondyloarthritis fulfilled definitions for long term opioid use within 12 months of starting an opioid. 

This proportion could be as high as 1 in 3 for those with fibromyalgia or rheumatoid arthritis and 1 in 3.5 for those with axial spondyloarthritis using the broad definition, say the researchers. 

Dr Joyce Huang, the research associate from The University of Manchester and first author said: “Our study does not intend to stigmatise patients who use opioids. We want to highlight the high frequency of long-term opioid use needs to be optimised and prevent people living with RMDs from opioid-related harm.”

Dr Meghna Jani, an NIHR Advanced Fellow and Senior Lecturer at the Centre for Epidemiology Versus Arthritis, The University of Manchester was the Principal Investigator of the study. “Our study shows that a considerable proportion of patients with RMDs starting opioids for the first time, transition to long-term opioid use. In RMD patients this is much higher than people who are starting an opioid for non-cancer pain in general- has shown that this was around 1 in 7 people.

“Because long-term opioid therapy is associated with poor health outcomes, these findings warrant vigilance when prescribing these drugs. Long term use is particularly pronounced in fibromyalgia patients, who suffer chronic widespread pain for which there are no disease modifying treatment options. This is also more common than we initially thought, in rheumatoid arthritis and axial spondyloarthritis.”

The authors advise prompt interventions such as medication reviews or deprescribing interventions in the community will ensure the appropriateness of long-term opioid therapy.

“Proactive consideration of non-pharmacological treatments for pain relief where appropriate would also be of benefit to reduce avoidable harm to these patients.”

Deborah Alsina MBE, Chief Executive of the charity Versus Arthritis, said:“People with arthritis experiencing relentless and excruciating chronic pain are often desperate for pain relief, and it is sometimes appropriate for doctors to prescribe opioids in the short term. If people benefit from opioids, then they should be able to access these medicines.

"However, there are some who have a negative experience taking opioids, including risk of dependence due to long term use. Others have found that opioids make no difference to their quality of life, for good or bad.

"The decision to take any medicine should always be shared between a person and their doctor. This research can be used by doctors to inform people with arthritis of the possible benefits and risks of opioids and whether it is the right medicine for them.”

High frequency of long-term opioid use among patients with rheumatic and musculoskeletal diseases initiating opioids for the first time doi 10.1136/ard-2023-224118 is published in the Journal Annals of the Rheumatic Disease

The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care 

The authors hope their findings – published today in journal Rheumatology – will ease the concerns of patients before commencing treatment, who often lack knowledge of the drug, its impact and side effects.

Though the study is unable to conclude if the drug causes the side effects they report in arthritis patients, the associations give them and their doctors – valuable information, argue the researchers.

The principle investigator, Dr Suzanne Verstappen from The University of Manchester, is supported by Versus Arthritis and 91ֱ�� BRC. The BRC’s aims to use biomarkers such as patient data, to predict outcomes and personalise treatments for patients with MSK conditions. 

The team evaluated data of 1,069 patients who participated in the Rheumatoid Arthritis Medication 91ֱ�� (RAMS) from 38 hospitals across the UK, including in Greater 91ֱ��. The patients were recruited to the study before starting methotrexate treatment and were followed up for one year.

At six and 12-months, 957 patients (89.5 per cent) and 902 patients (84.4 per cent) were still taking the drug orally, respectively.

However, 106 (9.9per cent) and 169 (15.8per cent) had switched to subcutaneous methotrexate by six and 12 months respectively.

Side effects were common among patients over the first year of methotrexate, though most were not serious.

Overall, 77.5per cent experienced at least one side effect during the 12 months: 250 reported only one, 169 reported two, and the others reported three or more.

Of the side effects associated with taking the drug:

• 42 per cent were gastrointestinal, including nausea (31per cent) and Diarrhoea (15per cent).
• 39.6 per cent were generalised, including fatigue (29 per cent).
• 28.6 per cent were neurological, including headaches (19 per cent) and dizziness (12 per cent).
• 26.0 per cent were mucocutaneous, including alopecia (9 per cent), and mouth ulcers (12 per cent).

Older age was associated with less reporting of gastrointestinal side effects, whereas women were more likely to report gastrointestinal, mucocutaneous, or neurological side effects compared to men.

Alcohol consumption at the start of treatment was associated with nausea, alopecia, and mucocutaneous side effects while taking the drug. Patients who had higher levels of concern about treatment reported more gastrointestinal side effects, particularly nausea.

PI of the RAMS study, Dr Suzanne Verstappen is a Reader in musculoskeletal epidemiology at The University of Manchester and a researcher for 91ֱ�� BRC’s Adult Inflammatory Arthritis research programme. She said: “Methotrexate has transformed the treatment of inflammatory arthritis and improved the lives of almost two  million people worldwide.

“But worrying about side effects could stop patients from initiating this important drug, or reduce adherence to treatment.

“These findings, however, provide patients and clinicians with insight into the management of patients with rheumatoid arthritis starting methotrexate.

“Their concerns can be lessened by stressing the benefits of the treatment alongside a more specific discussion about side effects.”

PhD researcher Ahmad Sherbini and first author of the manuscript from The University of Manchester, said: “Methotrexate is currently the drug of first choice for newly diagnosed patients with rheumatoid arthritis due to its low-cost and established efficacy.

“However, side effects associated with it have a considerable impact on treatment retention rates during the first year of treatment.

“Using the data in this study, patients can make informed decisions whether to start this drug and potentially increasing adherence to treatment.”

“It can also help identifying patients with higher risk of side effects who require frequent monitoring and additional GP visits. Ultimately and with further studies, treatment can be tailored to patients, and better resource utilisation can be achieved.”

Dr Natalie Carter, Head of Research Engagement at Versus Arthritis said: “Methotrexate can be a highly effective treatment in controlling inflammatory arthritis, but for many there can be sides effects and illness which causes worry and distress.

“Research like this is vitally important. It means that people with arthritis are better informed on the medications being suggested and can support them when navigating a sometimes confusing and complicated treatment regime, especially when first diagnosed.

“With a better understanding on the types of side effects caused by medication people with arthritis can have productive conversations with their rheumatology team about their treatments on what is working, what is not, and how they can tailor that treatment to get the best possible result in managing their condition.”

Image: open bottle of methotrexate drug—first used in the early 1950s ()

Placebo pain-relief is reproducible in patients with chronic pain compared to healthy volunteers according to a unique University of Manchester study.

In a research first, patients with high levels of psychological distress such as depression and anxiety experienced pain relief in a placebo experiment with inert cream they thought might help them.

And that, say the research team, could encourage clinicians to think about using alternative strategies other than pain medication. It could also, they say, manage pain better and reduce dependence on pain medication which can have unwanted side-effects.

Pain is experienced as a result of particular brain processes in the brain which are sometimes not fine-tuned as well as they might be. Placebo is a powerful way of positively harnessing the brains ability to take control of how we feel pain.

The study, funded by Versus Arthritis is published in Pain – the world’s leading journal in the field.

The cream was applied to the forearm of 60 osteoarthritis and 79 fibromyalgia patients as well as and 98 Healthy Individuals.

The placebo group was told this may or may not be a local anaesthetic cream, while the control group was told the cream was inactive.

They were then given laser pain and asked to rank the intensity of the pain before, during and after cream application, along with expectation of pain relief and anxiety.

The procedure was repeated after two weeks and the results were found to be the same.

The findings complement the team’s work on enhancing natural pain control, using ‘Alpha brain-wave entrainment’, a light therapy which tunes the brain to a particular frequency of 10 cycles per second – known as alpha frequency.

Alpha brain-wave entrainment was previously shown by the team to be associated with the expectation of pain relief in health volunteers and patients with chronic pain.

Professor Anthony Jones from The University of Manchester is the Director of the Human Pain Research Group (HPRG), which is based at Salford Royal NHS Foundation Trust, part of the Northern Care Alliance NHS Group.

He said “Chronic pain carries a huge socioeconomic burden and substantially impacts the quality of life of affected individuals.

“It is often difficult to treat- and many of these patients have to live with its effects - and resultant impacts on their mental health- day in day out.

“But this study shows for the first time that people with osteoarthritis and fibromyalgia can modulate their responses to experimental pain as efficiently as healthy individuals.

"There might be a way to treat these patients - and that’s exciting.”

Dr Manoj Sivan is an Associate Professor in the Leeds Institute of Rheumatology and Musculoskeletal Medicine at the University of Leeds and honorary senior lecturer at The University of Manchester.

He said: “What was previously considered to be a nuisance variable has now been shown to have substantial potential to improve patient outcomes in chronic pain.

“Understanding the neural mechanisms of placebo response enables us to tap in to this more to modulate pain perception and enhance the analgesic effect of other novel step-change treatments, such as our Smart Neurotherapies Platform.”

He added: “With the current crisis of overuse of opioids a concern for all clinicians, this research strengthens the evidence for using non-drug approaches to manage chronic pain and encourages an important cultural change in managing our patients”

Dr Andrea Power, Honorary Research Associate at the University of Manchester said: “Pain normally increases negative emotions, which in turn increases the subjective experience of pain.

“Conversely, analgesic administration induces the expectation of reduced unpleasant symptoms, which reduces anxiety and, consequently, actual symptoms of unpleasantness.

“That is why chronic pain patients have psychological co-morbidities such as anxiety, depression, pain catastrophizing and cognitive impairments.

“For this reason, the role of expectancy and anxiety in modulation of pain by placebo has a role in treating these patients.”

Val Derbyshire, who has Osteo Arthritis and Fibromyalgia and works with the Salford Fibromyalgia Support Group

She said: “Currently people are offered different treatments - including opioids- with varying levels of success. Some people despair of ever finding resolution for their pain, and will try almost anything however weird and wonderful it may seem, whilst others are suggestible to any option offered.

“Anything which can reduce the use of Opioids and the concomitant side effects has to be welcomed. Placebo has been shown to work for many individuals without any harmful side effects. Therefore I believe that it could be used more widely in the treatment of chronic widespread pain.”

The abstract is available  

People with long-term health conditions are 20 per cent more likely to suffer from pain on days that are humid and windy with low atmospheric pressure according to new research from University of Manchester scientists.

The study, funded by Versus Arthritis, was based on the experience of people with conditions such as arthritis, fibromyalgia, migraine and neuropathic pain from across the UK.

According to the research, the most important factor associated with worsening pain is high relative humidity.

, called , ran throughout 2016 and recruited over 13,000 people from all 124 postcode areas of the UK, from Orkney to the Isles of Scilly.

Using a smartphone app developed by healthcare software company uMotif, participants recorded daily symptoms while the local weather was determined from location data provided by the smartphone’s GPS.

This analysis looked at data from 2,658 people who provided daily data on most days for around six months. The participants had a range of different health issues, predominantly arthritis.

Humid days were most likely to be painful, whereas dry days were least likely to be painful. Low pressure and higher wind speed were also linked to more painful days, although to a lesser extent than humidity.

Despite many people believing pain to be influenced by temperature, there was no association observed, when averaged across the population. That said, cold days that were also damp and windy could be more painful. Rainfall was not associated with pain.

Although the weather is known to influence mood, and mood can influence pain, this pathway did not explain the findings. Even when accounting for mood, the weather-pain association persisted.

Professor Will Dixon, Centre for Epidemiology Versus Arthritis at the University of Manchester, led the study.

He said, “Weather has been thought to affect symptoms in patients with arthritis since Hippocrates. Around three quarters of people living with arthritis believe their pain is affected by the weather.

Yet despite much research examining the existence and nature of this relationship, there remains no scientific consensus. We hoped that smartphones would allow us to make greater progress by recruiting many more people, and tracking daily symptoms across seasons.

“The analysis showed that on a damp and windy days with low pressure the chances of experiencing more pain, compared to an average day, was around 20%. This would mean that, if your chances of a painful day on an average weather day were 5 in 100, they would increase to 6 in 100 on a damp and windy day.

“The results of this study could be important for patients in the future for two reasons. Given we can forecast the weather, it may be possible to develop a pain forecast knowing the relationship between weather and pain. This would allow people who suffer from chronic pain to plan their activities, completing harder tasks on days predicted to have lower levels of pain. The dataset will also provide information to scientists interested in understanding the mechanisms of pain, which could ultimately open the door to new treatments.”

Carolyn Gamble who has a form of arthritis called ankylosing spondylitis said: “So many people live with chronic pain, affecting their work, family life and their mental health. Even when we’ve followed the best pain management advice, we often still experience daily pain.

Having taken part in the study, she adds, “knowing how the weather impacts on our pain can enable us to accept that the pain is out of our control, it is not something we have done, or could have done differently in our own self-management.”

Dr Stephen Simpson, Director of Research at Versus Arthritis, said:

“We know that of the 10 million people in the UK with arthritis, over half experience life-altering pain every day. But our healthcare system is simply not geared up to effectively help people with arthritis with their number one concern.

“Supporting effective ways of self-managing pain can make all the difference for people with arthritis, helping them to get and stay in work, to be full members of the community and simply to belong.

“Will Dixon and his team and their collaborators have shown a remarkable spirit of innovation, pushing new boundaries to bring people with arthritis into research. This research will help us understand the bigger picture of the complexity of pain caused by arthritis and how people with the condition can take control of it.”

REFERENCE Dixon, W.G., Beukenhorst, A.L., Yimer, B.B. et al. How the weather affects the pain of citizen scientists using a smartphone app. npj Digit. Med. 2, 105 (2019)  / 

Oldham based doctor, has developed a new blood test which could help local rheumatoid arthritis patients to better manage their illness by keeping to their medication regimes.

Methotrexate is the most commonly prescribed drug for the 400,000 people in the UK suffering from this autoimmune disease. However, around 40% of rheumatoid arthritis (RA) patients do not take the drug as prescribed and, currently, clinical staff have no way of knowing whether a patient is taking their medication as advised.

Thirty eight year old, Dr Bluett practises at the borough’s which provides care for patients in orthopaedics, rheumatology and chronic pain. He is also a researcher for the and a Clinical Senior Lecturer at The University of Manchester.

The new test, developed, refined and assessed over 4 years, measures the methotrexate levels in a patient’s blood over the previous seven days. The final research results from 138 RA patients showed that the test has a 95% sensitivity in detecting whether someone took their methotrexate in the preceding week.

The initial evaluation of the blood test’s effectiveness was carried out in the with 20 patients from the North West.

“Patients may not take their methotrexate as prescribed for several reasons” said Dr Bluett, who splits his time equally between clinical practice and academic research at The University of Manchester. “Methotrexate is a weekly treatment, taken over a long period and can have side effects. Non-adherence means the drug won’t work as effectively and risks a patient’s condition worsening.

“Our new marker will enable doctors to start supportive conversations with patients about the difficulties they may be experiencing with the medication and how to resolve them.”

Dr Bluett was appointed as a consultant at the specialist musculoskeletal service, on New Radcliffe Street, in April 2018. The service, commissioned by NHS Oldham Clinical Commissioning Group, receives nearly 15,000 new referrals a year, mainly from local GPs and provides long term support for nearly 1,500 people with rheumatoid arthritis.

Dr Bluett’s  was published this month in the world’s leading rheumatology journal: the Annals of the Rheumatic Diseases.

“We need to see whether RA patients’ adherence improves when they receive feedback on their methotrexate levels. So, the next step will be a feasibility study to assess how we can gauge this in a clinical trial.

“I hope this further work validates our approach which could then, after appropriate regulatory approval, be incorporated into routine clinical practice. I want to ensure the best outcomes for RA patients” concluded Dr Bluett.

The Medical Research Council  funded 91ֱ�� Molecular Pathology Innovation Centre part funded the work.

A class of drugs which have been successfully treating patients with severe rheumatoid arthritis should be made available for moderate suffers too, University of Manchester scientists say.

A study led by Dr James Gwinnutt reveals that some rheumatoid arthritis patients who do not qualify for biological treatments on the NHS have high levels of disability caused by the condition. It is published in the journal .

The research, funded by Versus Arthritis is part of the Moderate Disease Activity in Rheumatoid Arthritis 91ֱ�� (MODRAS) directed by Dr Suzanne Verstappen from The University of Manchester.

Biologics are genetically engineered compounds which work on our immune system to reduce inflammation.

They have revolutionised treatment since they were introduced in the late 1990s.

Using data from 1,274 patients from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis, the team, looked at disability scores over 3 years of patients with moderate disease activity receiving conventional treatments for rheumatoid arthritis.

The study of the BSRBR-RA , whose Chief Investigator Professor Kimme Hyrich, included researchers from the University of Manchester and King’s College London.

The data revealed that over three years, some of the people with moderate disease which didn’t fulfil the NHS criteria for biologic treatment had very high levels disability.

Previous randomised trials assessed by the team also showed that the treatments can help patients with moderate disease activity.

The NHS currently uses a disease activity score to assess if a patient is eligible for biological therapy treatment. The measure incorporates swollen and tender joint counts, blood test of inflammation and the patient’s assessment of their disease.

Only patients with a score greater than 5.1 and have failed two conventional therapies are currently only able to receive treatment with biologics.

Lead researcher Dr James Gwinnutt said: “Our study has shown that there is a definite mismatch between the levels of disability some patients endure and the criteria by which the NHS measures their eligibility for biological treatments.

“This research does seem to suggest that it this group of patients with moderate rheumatoid arthritis should be entitled to the biological therapies other suffers get.

“Better access to these successful drugs has the potential to change these peoples’ lives for the better.”

Dr Suzanne Verstappen said: “In many countries rheumatoid arthritis patients with moderate disease activity are successfully treated with biologics. This study shows that there are groups of patients with moderate disease activity which have a poor progression of their disease and would benefit from more aggressive disease management including treatment with biologics.”

Results from a large clinical trial indicate that patients with rheumatoid arthritis are likely to experience the same level of cardiovascular benefits from statins as other individuals, without additional risks. The findings appear in , an official journal of The American College of Rheumatology.

The paper’s lead author is Professor George Kitas of Dudley Group NHS Foundation Trust, while co-senior authors are Professor Jill Belch of the University of Dundee and Professor Deborah Symmons of the University of Manchester.

Patients with rheumatoid arthritis have an approximately 50 percent higher risk of experiencing cardiovascular events such as heart attack and stroke compared with the general population. By lowering LDL cholesterol, statins are known to help prevent cardiovascular events in certain high-risk individuals, but it’s unclear whether they are safe and effective for patients with inflammatory conditions such as rheumatoid arthritis.

To investigate the potential risks and benefits of statins in moderate risk patients with rheumatoid arthritis, researchers designed the Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (TRACE RA), a multi-center, randomized, double-blind trial comparing the statin atorvastatin with placebo.

The trial included 3,002 patients with rheumatoid arthritis who were over aged 50 years or had rheumatoid arthritis for more than 10 years, without clinical atherosclerosis, diabetes, or myopathy. Patients were randomized to receive atorvastatin 40mg daily or placebo.

During a median follow-up of 2.5 years, 1.6 percent of patients who received atorvastatin and 2.4 percent of patients receiving placebo experienced cardiovascular death, heart attack, stroke, transient ischemic attack, or any arterial revascularization. After adjustments, there was a 40 percent lower risk of cardiovascular events for patients taking atorvastatin, although the difference was not statistically significant. This was because the overall rate of events was low.

At the end of the trial, patients taking atorvastatin had significantly lower LDL cholesterol as well as significantly lower levels of C-reactive protein, a marker of inflammation, compared with patients taking placebo. Adverse events in the atorvastatin and placebo groups were similar.

The paper’s lead author is Professor George Kitas of Dudley Group NHS Foundation Trust, while co-senior authors are Professor Jill Belch of the University of Dundee and Professor Deborah Symmons of the University of Manchester.

“The trial found that the statin reduced levels of cholesterol by similar amounts as has been seen in other populations studied. The results also show that it is as safe for patients with rheumatoid arthritis to take statins as for the general population,” said Prof. Symmons. “In addition, because of the low overall rate of cardiovascular events in the trial population, there is no indication for all patients with rheumatoid arthritis to be prescribed a statin. This is unlike diabetes where the great majority of patients are recommended to take a statin.”

The study authors recommend that patients with rheumatoid arthritis be prescribed statins according to national or local guidelines for managing cardiovascular risk in the general population.

An accompanying editorial notes that the study provides information that will be useful for researchers and clinicians who focus on rheumatoid arthritis, and the results may be helpful when considering cardiovascular risk across other rheumatic diseases.

“Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (Trace Ra): A Multicenter, Randomized, Placebo Controlled Trial.” George D. Kitas, Peter Nightingale, Jane Armitage, Naveed Sattar, Jill J.F. Belch, and Deborah P.M. Symmons, on behalf of the TRACE RA consortium. Arthritis & Rheumatology; Published Online: April 15, 2019 (DOI: 10.1002/art.40892) is published .

Scientists at The University of Manchester have discovered that most people with osteoarthritis can be subdivided into two distinct disease groups, with implications for diagnosis and drug development.

based at The University’s and says the team has identified two different patterns of disease activity.

The research, funded by , is published in the international journal,

The discovery of the two disease groups was made by using mathematical analysis of the thousands of genes expressed from tissue obtained from 60 individual patients with knee osteoarthritis.

As the stratification is based on active metabolism in the diseased tissue, the team believe it may help predict different patient responses to treatment.

Osteoarthritis is a complex and debilitating disease which affects more than 8 million sufferers in UK, which is increasing as the population ages.

Professor Hardingham said: “This is an important new discovery in Osteoarthritis, which reveals a metabolic basis for developing patient specific treatments targeted at the two different groups

“It will inform the future design, set up and analysis of drug trials and may help predict different patient responses to treatment.

“There is an urgent need for better treatments and we hope this research may help us along that road.

“Musculo-skeletal conditions cost the NHS £4.76 billion per year in 2013-14 and there has been little advance in the treatments for osteoarthritis over that past 30 years; new approaches tested have yielded little benefit.”

The team also developed a more simple method of analysis, generating a list of candidate biomarkers for detection in patients’ synovial fluid - found in the cavities of joints - to distinguish patients in the two Groups

They hope the analysis will help future research.

He added: “This is a significant step forward in our understanding of osteoarthritis, a complex and debilitating disease which has a major socio-economic impact.

“However, the discovery is just the first step in a long process that may lead to developing new drugs and treatments that are targeted to each group.”

“The disease has many clinical criteria and treating it as a single disease has become recognised as unproductive.

“So any new treatments which delayed the onset, or reduced progression of osteoarthritis in either group, would relieve much patient suffering and reduce the healthcare burden.”

Dr Natalie Carter, head of research liaison and evaluation at Arthritis Research UK, comments:

“We know that millions of people live with the daily pain of osteoarthritis. This, coupled with stiffness and fatigue, can make everyday life difficult, limiting a person’s ability to get dressed, go to work or even climb the stairs.

Although it’s still very early days, this study is good news for people with osteoarthritis and helps us to build on our understanding of the condition. We welcome more research, like this study, that has the potential to improve the way we understand, diagnose and treat osteoarthritis and so that people with arthritis can live the pain free life they deserve.”

” is published online in Annals of the Rheumatic Diseases.

The National Rheumatoid Arthritis Society has announced findings from a study conducted in partnership with The University of Manchester that investigates the impact of Rheumatoid Arthritis and adult Juvenile Idiopathic Arthritis  in the workplace.

NRAS surveyed more than 1,500 people in the UK to see how the life-long, debilitating illness affects their career and employers’ attitudes. NRAS last ran such a wide-ranging survey in 2007.

Despite 97% of people with RA feeling that they are being more open about their condition at work, a rising number of employers still do not understand the illness and its symptoms. Working participants believe having “time off when feeling unwell or experiencing a flare up” is the biggest barrier that they currently face at work, with more than a third (37%) ranking this as either a serious or very serious problem.

This is closely followed by “lack of support from an employer or line manager” and one in four of those working with RA find the “lack of understanding from their colleagues” to be a serious problem.

Musculoskeletal illnesses are amongst the highest causes of lost workdays in the UK and although more than 400,000 people in the UK are living with RA, awareness for the debilitating condition remains low – as once again proven by this comprehensive study.

There has been notable progression in the workplace over the last decade – nearly two thirds (63%) of people with RA are in employment today compared to 55% in 2007. Yet, more than half of the participants would feel unable to continue work if their job became more physically or emotionally demanding, highlighting the need for appropriate support in the workplace.

More than a third (39%) of respondents cite that their employer doesn’t understand the disease, compared to 29.5% in 2007. Awareness levels are critically low at small and medium-sized enterprises (SMEs) in particular, which are unlikely to have an internal HR department.

Short of half of those surveyed (41.5%) have had to change jobs since the onset of the illness and 15% were even forced to stop working altogether. The survey has revealed that, unfortunately, only half of those working were offered adjustments such as flexible working, reduced hours or special equipment in their last job.

RA also impacts on financial and job security – 39% of people with RA find themselves having had to take on part-time positions and 48.5% of respondents would feel “rather or very insecure” if their condition prevented them from working for a longer period of time. This can, in turn, lead to anxiety and depression – with mental health issues being the second-highest cause of lost workdays in the UK.

Matthew Bezzant, Policy and Public Affairs Manager at NRAS, commented on the findings: “It’s really interesting to see how the evolving workplace is affecting people with auto-immune conditions like RA. As the adoption of flexi-working increases and new laws to protect employees come into place, there is still a need for companies to invest time understanding these conditions, especially as desk-based work is continuing to increase.”

Bezzant added: “To be progressive, HR teams around the UK and managers of smaller businesses need to understand that conditions like RA are manageable in the workplace. Our Work Matters survey highlights that businesses in the UK need access to information on how to create a flexible and supportive working environment in order to adopt this. Sadly, less than half of those surveyed were offered supportive changes in their last job; easy adjustments like flexible working hours, shorter days or special equipment. Ultimately, a physical disability should not limit individual career success.”

Dr Suzanne Verstappen, Reader at the Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, School of Biological Sciences at the University of Manchester, added: “For many people with rheumatoid arthritis and adult juvenile idiopathic arthritis (JIA) work is important. I have been researching people with arthritis and the workplace for more than 15 years now. Although it seems there is growing awareness of the impact RA has at work, this survey highlights again that many people struggle in their careers and have to retire early. It also shows that there are various factors that determine whether people find it difficult to perform their job (e.g. understanding and help from colleagues and/or manager, reasonable adjustments, demands of job, flexible hours).”

She concluded: “In addition, this research provides a unique insight into the experiences of young adults planning their career and early employment. Results indicate a lack of structured support within schools/universities for young people with chronic condition(s). The results of this are very important and will inform patients, employers, health care professionals and policymakers about possible interventions in the workplace and future policies to prevent problems at work and job loss.”

The University of Manchester is part of a national consortium which has been awarded a £1.7 million grant to create the world’s largest Immune-Mediated Inflammatory Disease (IMID) Biobank, in excess of 40,000 patients.

The Medical Research Council (MRC) funded project will be delivered by the IMIDBio-UK consortium, which brings together researchers from the University of Glasgow, Newcastle University, the University of Cambridge, Queen Mary University of London and the University of Manchester.

The biobank will enable more precise treatment of immune-mediated inflammatory diseases, common medical conditions that cause substantial pain, distress, loss of function and early death. They include rheumatoid arthritis (RA), psoriasis, systemic lupus erythematosus (SLE), Sjogren's syndrome and autoimmune hepatitis. 

Led by Professor Iain McInnes, Director of the University of Glasgow’s Institute of Infection, Immunity and Inflammation, the IMIDBio-UK project will incorporate MRC, National Institute for Health Research and Scottish Government Chief Scientist  funded biobanks and clinical datasets into one single, searchable and analysable ‘superhighway’, allowing unprecedented access to information about IMIDs across the UK.

The University of Manchester will provide expertise on inflammation medicine particularly with respect to inflammatory skin and joint disease. It also hosts the 91ֱ�� Molecular Pathology Innovation Centre which facilitates the translation of personalised medicine research into usable tests that can be implemented within the NHS (a remit reliant on access to high quality patient samples).

Professor Chris Griffiths, University of Manchester, Foundation Professor of Dermatology and IMIDBio-UK Co-Investigator, said: “The formation of IMID-Bio UK is an important first step in uniting the UK’s resources and expertise in personalised care for inflammatory disease. The 91ֱ�� team is delighted to be part of this consortium and the opportunities it will provide to enhance patient care.”

This superhighway of information will provide the kind of large scale data needed to apply a precision medicine approach to these health conditions. Researchers hope that it will soon be possible to create a 'molecular map' of a patient, which would ultimately allow doctors to be able to prescribe more effective, less toxic drugs to patients, based on their individual condition.

Professor Iain McInnes, Muirhead Chair of Medicine, said: “IMIDBio-UK is a unique opportunity to bring together the strengths of inflammation medicine from across the United Kingdom.

“By working together we will learn from cohorts of patients with seemingly different conditions, such as psoriasis, arthritis, kidney and liver disease, and bring them together to shed new light on the specific causes of each condition individually, but also we hope to find common pathways that drive them collectively.

“Using this knowledge in future we will be able to seek new medicines, and importantly, by applying the principles of precision medicine, we will be able to use these new medicines in the right person, at the right time, and at the right dose.”

The IMIDs are clinically diverse, variously targeting the skin, joints, or kidneys, but share some common genetic features, environmental triggers and inflammatory mechanisms. Since the 1990s, drugs and improved treatment strategies have revolutionised the treatment of a significant proportion of people with some IMIDs. However some IMIDs have not really progressed and even in those in which advances are notable, many patients do not yet respond to treatment or lose their responses over time.

Until now, most IMID collections of data have been specific to only one disease, leading to a narrow approach to the broader inflammation medicine field. 

Researchers hope that this project will enable wider, safer use of biologics and new medicines across the IMID spectrum. By bringing together samples and comparing data and clinical practice, it will optimise clinical pathways for common IMIDs, and provide much needed insight into biologic use in rarer or poorly characterised IMIDs, ultimately delivering patient benefit and health care savings.

The University of Manchester is part of a new consortium which will develop new CT and MRI scan techniques and biomarkers to look at the accumulation of compounds in the body caused by drugs and the harm they may cause – potentially improving patients’ safety and the development of new treatments.

The TRISTAN project, (Translational Imaging in Drug Safety Assessment) is a public-private partnership supported by involving organisations across Europe. The University of Manchester is a major part of this, receiving funding to develop scanning techniques for so-called imaging biomarkers for drug-induced liver and lung disease.

The researchers believe that by refining these techniques to adapt scans for specific compounds they can spot the early signs of disease, tailor individual treatments and identify problems with new drugs early in their development – potentially saving time and money.

One part of the package will be to develop a trial in rheumatology and patients who have drug induced lung toxicity. By scanning them, the researchers hope to refine techniques to spot this early on and identify which patients are most susceptible.

, a National Institute for Health Research Clinical Lecturer in Rheumatology, who is leading this part of the research in 91ֱ��, said: "Some drugs can cause inflammation and damage in the lungs. We hope to develop scans that can identify early lung changes so that quick action can be taken to minimise harm to the patient. The scans may also help identify drugs which are at high risk of causing lung problems so they are not developed further.”

Another part of the project will investigate drug interactions and drug-induced liver disease. Specifically the researchers will look for the presence of imaging biomarker gadoxetate in liver cells. This will enable them to develop predictive models to help with the development of new drugs with less safety concerns.

, principal investigator and Reader in the School of Health Sciences/ Pharmacy, is leading this section of the project. She said: “Quite often drugs are far down the line of development before potential harmful side-effects are discovered. Use of imaging biomarkers and predictive models could help identify a drug that is not a good candidate much earlier, saving a lot of money and research time.”

Overall the five-year, European-wide project is budgeted at €24m. TRISTAN is led by Bayer and coordinated by the European Organisation for Research and Treatment of Cancer (EORTC). The University of Manchester will receive around £1.1m. Partners in this part of the work will be the University of Leeds, University of Sheffield/Sheffield Teaching Hospitals NHS Trust.

It will also involve The University of Manchester spin-out company Bioxydyn, a specialist provider of ground-breaking MRI applications and imaging services.

, a co-investigator and Director of (BRC) said: “Researchers across Greater 91ֱ�� are working towards a more personalised approach that matches individuals to the treatment most likely to work for them. This grant from the European Commission will complement the funding for our new BRC and support research into the use of advanced imaging biomarkers to better predict targeting of treatment and reduce the risk of side effects.”

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 is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet. #ResearchBeacons

People living with Rheumatoid Arthritis have experienced significant improvements in their daily lives which is probably down to early and more aggressive treatment of the disease, according to new research from The Universities of Manchester and East Anglia.

James Gwinnutt, first author of this study from The University of Manchester, conducted the Arthritis Research UK study, led by Dr Suzan Verstappen University of Manchester, into the devastating disease which examined 20 years of data from 1990 to 2010.

The 602 patients in this study, Published in Arthritis and Rheumatology, were recruited to the Norfolk Arthritis Register (NOAR: Chief Investigator Professor Alex MacGregor University of East Anglia) and assessed at regular intervals over the course of 20 years.

The team found that patients who were prescribed disease modifying drug therapies such as sulfasalazine, methotrexate and steroids within 6 months of symptom onset experienced significantly better ability to walk, grip and dress themselves over the course of 20 years compared, to patients who were treated later.

And patients who received these disease modifying drug therapies within the first 6 months had a lower risk of dying, after controlling for the severity of the disease.

Mr Gwinnutt said: “This research shows that patients who received treatment early after symptom onset had similar levels of disability over the subsequent 20 years compared to patients who were judged by clinicians not to require treatment, after accounting for the differences in disease severity between the groups.

“Though there is a broad range in terms of how people are affected by the disease, the number of patients whose lives have improved has increased thanks in part to early treatment.”

He added: “The good news is that early intervention has become more and more common in the NHS over these past 20 years.

“In the early 1990s early intervention would happen in about 30% of cases. Nowadays, that figure is probably more like 60-70%.

“There’s no reason why this improvement could not extend further.”

Dr Natalie Carter, head of research liaison and evaluation at Arthritis Research UK, comments;

“Rheumatoid arthritis is an incredibly painful condition that can be diagnosed at any age and can have an impact on a person’s everyday life. This study confirms how important early diagnosis and the commencement of treatment is. It is also encouraging to hear about the progress that has been made over the last 20 years.

Now the scientific community must continue to build on this so that together we can continue to harness the power of exceptional science and make everyday life better for all people with arthritis.”

Rheumatoid arthritis is an autoimmune disease that causes joint inflammation and pain.

It is the second most common form of arthritis in the UK and around 1% of the adult population suffer from it.

There have been major advances in available treatments and strategies for the management of RA over the past 20 years.

People taking a common rheumatoid arthritis medicine are not at increased risk of liver damage if they stick to 14 units of alcohol a week or fewer, a new study from The University of Manchester has found.

Methotrexate is a drug taken, often over long periods of time, to limit or prevent joint damage and disability. People who take methotrexate are often advised to abstain from alcohol as both methotrexate and alcohol are known to increase the risks of liver damage. However, it is not known whether drinking modest amounts of alcohol is safe during methotrexate therapy.

The new study by The University of Manchester, published in the journal Annals of the Rheumatic Diseases and funded by , has drawn upon the medical records of almost 12,000 people with rheumatoid arthritis taking the drug who had a record of the levels of alcohol they drank and who had routine blood monitoring test results.

The researchers found that increased use of alcohol did indeed correspond to increased liver damage, but at 14 units or fewer there was no heightened risk.

Dr Natalie Carter, Head of Research Liaison and Evaluation at Arthritis Research UK, said: “We know that methotrexate can be an effective drug for treating arthritis. As it can interact with other medicines and alcohol it is important that people with arthritis have information about their medication in order to manage their arthritis safely and effectively.

Arthritis Research UK invests in exceptional science to find treatments and information that let people push back the limits these conditions cause. This research adds to the knowledge we have around methotrexate and its effects in people with rheumatoid arthritis, which can help people make informed decisions about their treatment. We would recommend that people who take methotrexate to speak to their rheumatologist for advice about drinking alcohol whilst on this drug.”

, an NIHR Clinical Lecturer at The University of Manchester’s , led the study. She said: “In the past there’s not been clear guidance on what effects different amounts of alcohol have on these people, so doctors often err on the side of caution and recommend abstinence.

“As a result, some people choose to decline methotrexate so they can continue to enjoy a drink, thereby missing out on the possible benefits of the medication. Alternatively, some people may go totally without alcohol after starting methotrexate: if they like to drink in moderation, the quality of their life may be affected.”

With a pint of 5.2% ABV beer containing three units and a 250ml glass of 14% ABV wine containing 3.5, the findings show that people can drink in moderation, while still benefitting from the drug.

The data used in the study came from the , a UK general practice database. The researchers identified 11,839 people with rheumatoid arthritis who were taking methotrexate and had at least six liver function test results per year. Of these, 530 developed abnormal liver function tests.

Although there was no increased risk associated with drinking 14 units or less compared to people who drank no alcohol, people who drank 15-21 units had a 33% increased probability of liver damage and this rose to 81% in the group that drank more than 21 units.

, Director of the Arthritis Research UK Centre for Epidemiology at The University of Manchester, who is also a rheumatologist at Salford Royal NHS Foundation Trust, believes that the results can provide important guidance for doctors who are prescribing methotrexate.

Paper: , Jenny H Humphreys, Alexander Warner, Ruth Costello, Mark Lunt, Suzanne MM Verstappen, William G Dixon. Published in the Annals of Rheumatic Diseases.

91ֱ�� researchers have established a new social enterprise, , to support the development of new tests and treatments for musculoskeletal conditions, including rheumatoid arthritis.

Musculoskeletal conditions have a significant impact on people’s quality of life and are a huge burden on society. In the UK, around 21% of the population consults with a GP about musculoskeletal complaints each year and this figure is set to rise, as the population ages.

Over the past 20 years, researchers at The University of Manchester have established a uniquely rich collection of biological samples and data. This resource is now being opened up to other researchers through Inspiral Biomedical Limited.

Professor of Rheumatology at The University of Manchester and Chairperson of Inspiral Biomedical Limited, , explains: “We know that our bank of biological samples and data holds an unprecedented opportunity to gain a better understanding of these conditions and how best to treat those individuals affected.

“In 91ֱ��, we are already utilising this resource, but by making it available to other academic and industry researchers across the world will be able to bring new tests and treatments to patients more quickly.”

The researchers believe that the richness of the data and samples available from patients spanning a variety of musculoskeletal conditions, obtained before, during and after treatment, make this resource globally unique.

Further information about the samples and data available, and how to make an application to access the resource is available at: .

A biologic drug which treats rheumatoid arthritis has been shown by new research to reduce the risk of heart attacks in arthritis sufferers by up to 40 per cent.

Patients with rheumatoid arthritis (RA) have a 60 per cent higher risk of heart attacks than the public, thought to be linked to the inflammation caused by the disease on affected joints. Reducing inflammation is a key goal of medical interventions, and several types of treatments are used.

Biologic drugs, such as tumour necrosis factor inhibitors (TNFi), work by reducing or eliminating certain proteins that cause inflammation. Synthetic disease modifying therapies (sDMARD) are used to slow down progression of rheumatoid arthritis and include drugs like methotrexate.

Current guidelines in the UK restrict the prescribing of TFNi in RA patients only to those with a sustained and highly active disease which has failed to respond to therapeutic doses of sDMARDS. Other patients with persistent inflammation which is at a more moderate level despite sDMARDs are not eligible. It is estimated that around 15% of patients with RA are receiving biologic therapies.

Researchers from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) at the Arthritis Research UK Centre for Epidemiology at The University of Manchester, studied two groups of RA patients to determine both heart attack risk and the severity of attack when occurred.

The first group, 11,200 strong, was for those receiving TNFi drugs, while remaining 3,058 patients were taking only sDMARDs.

Over three to five years of clinical and records follow-up, the researchers noted that risk of heart attacks was reduced by almost 40 per cent in patients who received TNFi compared to those who had received sDMARD only.

Kimme Hyrich, Professor in The University of Manchester’s Division of Musculoskeletal & Dermatological Sciences, led the BSRBR-RA’s research team and said: “Rheumatoid arthritis patients already have to endure a debilitating condition, but to have an elevated risk of heart attacks because of their disease is a very worrying complication. In addition to managing risk factors such as high blood pressure and high cholesterol, achieving excellent control of inflammation can also reduce this risk.

“Our team has been able to show that this elevated risk can be reduced significantly by using biological drug therapies such as TNFi. The prescribing guidelines for TFNi therapies are very specific, and for good reason.

“However, the biologically plausible explanation for our findings – not only that TFNi reduces the inflammation associated with atherosclerosis but that it also may inhibit the accumulation and progression of plaque leading to fewer heart attacks – could be used to review existing guidelines and in particular, extend the use to patients with moderate levels of disease activity.”

Another member of the research team, the majority of whose research is funded by the British Heart Foundation is University of Leeds Associate Professor of Cardiovascular Health Sciences and Honorary Consultant Cardiologist, Dr Chris Gale. He said: “This study, which linked the national registry of patients with rheumatoid arthritis with the national health attack registry, shows a striking relationship between the use of biological treatments for rheumatoid arthritis and reduced risk of heart attack.

“Clearly, further research is needed to investigate the cellular mechanisms behind this, but also to test whether immunosuppressive agents may reduce the risk of heart attack in other high risk populations.”

Stephen Simpson, Director of Research and Programmes at Arthritis Research UK, said: “This promising research could make a real difference to people with arthritis who live with the knowledge that they are have an increased risk of having a heart attack. We are delighted that our funding is helping find ways to understand and reduce that risk and help give people the everyday freedom they need from the limits of arthritis.”

Another research outcome related to the severity of heart attacks that did occur in the total study cohort. There was no difference in the severity of heart attacks among those who did suffer a myocardial infarction while on either drug therapy. So while TNFi treatments did reduce the risk of experiencing a heart attack, it showed no impact on the severity – and overall survivability – of heart attacks among RA patients.

The research team worked with the Myocardial Ischaemia National Audit Project, as mentioned by Professor Gale, to assist in grading heart attack severity and also the Health and Social Care Information Centre to access reporting of deaths.

Dr Mike Knapton, associate medical director at the British Heart Foundation, said:

“Patients with the painful and disabling condition rheumatoid arthritis also have a 60 to 70 per cent increased risk of a heart attack. This research is interesting, showing a clear association between receiving TNFi and risk of heart attack, however, it does not actually confirm that the biological drug causes the reduction in risk of heart attack.

“This research will inform future work, as we discover new ways to reduce heart attacks in people living with rheumatoid arthritis.

"In the meantime it is important that patients with rheumatoid arthritis should not only be offered treatment for their condition, but also offered management to reduce their risk of a heart attack – including managing blood pressure, cholesterol and lifestyle factors such as diet and exercise.”

A group of young designers from 91ֱ�� are launching a new exhibition on Monday, 5 December, showcasing innovative designs at 91ֱ�� Art Gallery to help raise awareness of musculoskeletal disorders.

#DesignforMSK, is supported by NIHR 91ֱ�� Musculoskeletal Biomedical Research Unit, jointly run by The University of Manchester and was delivered by the Public Programmes Team at Central 91ֱ�� University Hospitals NHS Foundation Trust. It aims to highlight the experiences of young people with musculoskeletal conditions via an exhibition of new products designed collaboratively to support the daily life of those with the conditions.

Many believe that musculoskeletal conditions only affect older generations, but thousands of young people are also living with these painful and debilitating conditions.

Musculoskeletal conditions in young people include autoimmune diseases, such as lupus and arthritis. This means that the body’s own immune system, which normally protects us against harmful bacteria and other pathogens, starts attacking the body. This can lead to pain, swelling and damage to the joints and other parts of the body. Along with fatigue and other limitations, this can make daily life a challenge.

The group, made up of four designers, three medical researchers, twelve young people and three curators, have held numerous workshops over the past few months to develop attractive but functional products to help overcome the obstacles young people with musculoskeletal conditions face every day.

A key feature of many of the products is their ability to be personalised or to adapt to fit the user’s own style. A seat and back support, with the appearance of a large, geometric necklace, can be adjusted by the user to suit their individual needs.

Another design is adaptable bag straps, which have been created to attach to any fashionable bag. Often, thin straps cause discomfort for people with musculoskeletal conditions, so the wide strap attachment helps to spread the weight of the bag across a wider area as well as containing pockets for either heat or ice packs to soothe joint pain.

Zainab Saleem, 23 years old from Chorlton, was diagnosed with Rheumatoid Arthritis at 19. She explains: “We met as a group for the first time in August to talk about the day-to-day issues young people with musculoskeletal conditions face. It was great to hear all the suggestions and solutions that came out of the group. Being a young person with a condition, you don't want to be treated differently when in groups or with friends. This can be the case if you need to use certain products, such as a walking stick or wrist splint.

“I think that product design can give users more confidence when using these products. The highlight of the #DesignforMSK process for me would be making a number of friends. After participating in the workshops I now feel I'm not alone and I am glad I can provide support to others.”

Susannah Williams, #DesignforMSK Project Manager from the Public Programmes Team, said: “This has been a really exciting and rewarding project for all involved. It has been wonderful to see the product ideas grow and develop, as well as to see the personal benefit being involved in the project has had for the participants.

“Because of the varied themes that came up in our group discussions, we have expanded the exhibition to include artists’ interpretations of being a young person with a musculoskeletal condition, as well as the product prototypes. We hope that #DesignforMSK: the Invisible (Visible) raises awareness that musculoskeletal conditions don’t just affect older people, and showcases designs that really could make a difference to young people’s lives.”

More details on the exhibition are available on .

Twitter / Instagram: @DesignforMSK

Facebook:

Preliminary findings from a mass participation study have indicated a link between weather conditions – specifically rain and lack of sunshine – and chronic pain.

Daily data inputted from over 9000 UK participants in The University of Manchester-led ‘’ project has been viewed at the halfway stage of the 18-month study; these early results suggest a correlation between the number of sunny days and rainfall levels and changes in pain levels.

Professor Will Dixon, who leads the study, spoke at at on Wednesday 7 September about this novel study and the interim findings.

Members of the public who have long-term pain record their daily pain symptoms on a special app. The app also independently captures hourly weather conditions using the smartphone GPS, thus joining pain data with real-time local weather events. The study is still open to new participants and the researchers are keen to recruit as many people as possible who are willing to track their symptoms.

At the halfway stage the research team reviewed the interim data, looking specifically at data sets collected from participants in three cities – Leeds, Norwich and London.

Across all three cities, as the number of sunny days increased from February to April, the amount of time spent in severe pain decreased. However, the amount of time spent in severe pain increased again in June when the weather was wetter and there were fewer hours of sunshine.

, Professor of Digital Epidemiology at The University of Manchester’s School of Biological Sciences and scientific lead for the Cloudy project, said the early results were encouraging but urged more people to take part in the study in order to allow robust conclusions at the end of the study.

“Once the link is proven, people will have the confidence to plan their activities in accordance with the weather. In addition, understanding how weather influences pain will allow medical researchers to explore new pain interventions and treatments.

“To work out the details of how weather influences pain, we need as many people as possible to participate in the study and track their symptoms on their smartphone.

“If you are affected by chronic pain, this is your chance to take do something personally – and easily – to lead to a breakthrough in our understanding of pain.”

People interested in joining the Cloudy with a Chance of Pain project – and who have access to a smartphone – can sign up at .

An exciting new project called #DesignforMSK has been launched by (BRU), inviting young people to work with product designers, and researchers to design new products to help improve daily issues faced by those with musculoskeletal conditions.

#DesignforMSK is looking for volunteers aged between 16-26 years old who have a musculoskeletal condition, to take part in three fun and interactive lunchtime workshops on the 12th, 27th August and 1st October at , Edge Street, 91ֱ��, to work together to design products to be turned into prototypes.

Many believe that arthritis and other musculoskeletal conditions only affect older generations, but thousands of young people are also living with these painful and debilitating conditions.

Musculoskeletal conditions in young people include autoimmune diseases, such as lupus and arthritis. This means that the body’s own immune system, which normally protects us against harmful bacteria and other pathogens, starts attacking the body. This can lead to pain, swelling and damage to the joints and other parts of the body. Along with fatigue and other limitations, this can make daily life a challenge.

University of Manchester graduate Simon Stones was diagnosed with juvenile idiopathic arthritis at the age of three and fibromyalgia at the age of 18. Simon explains why this project is so important in raising awareness of musculoskeletal conditions in young people: “This project is a great initiative whereby patients can work alongside researchers and designers to design solutions for people living with musculoskeletal conditions, to make everyday life a little bit easier.”

Working in collaboration with , the NIHR 91ֱ�� Musculoskeletal BRU aims to not only raise awareness about musculoskeletal conditions in young people but gives those with such conditions an active role in finding solutions.

, Professor of Genetic Epidemiology at The University of Manchester and NIHR 91ֱ�� Musculoskeletal BRU Theme Lead for Inflammatory Arthritis in Children said: “#DesignforMSK provides an opportunity for young people, alongside designers and researchers, to get involved in finding practical solutions to difficulties faced every day as a result of their conditions.

“We hope the workshops will also promote discussion amongst the groups, inspiring researchers to explore new ways to improve the quality of life for individuals with these conditions and to actively involve young people in developing innovative research projects in the future.”

The very best ideas from the workshops will be developed into prototypes of products and will go on display at an exhibition in 91ֱ�� later in the year.

Those who can’t attend can join in on Instagram, Twitter and Facebook by submitting images that depict the way musculoskeletal conditions affect your life, just search for #DesignforMSK. The images will then be used by art students at 91ֱ�� Metropolitan University to inspire new products that could make lives easier and more enjoyable.

Further information about the workshop:

The design workshop is open to anyone between the ages of 16-26 with a musculoskeletal condition. Reasonable travel costs will be covered, refreshments will be provided, and participants will be given a shopping voucher as a thank you for taking part.

• Friday 12th August 11am-2pm
• Sat 27th August 1-4pm
• Sat 1st October 1-4pm

For more details or to sign up, please visit , follow us on or Instagram @designforMSK, find us on or email publicprogrammes@cmft.nhs.uk.

The University of Manchester team behind a ground-breaking study recording how thousands of people with chronic pain react to the weather is seeking help from the public to come up with explanations for the results.

More than 8,000 people from all over the UK have downloaded the Cloudy with a Chance of Pain app and over a million pieces of data have been entered since the launch in January. Now the scientists are seeking to public’s help to draw links between the weather data and the recordings of pain.

Dr Will Dixon, Director of The University of Manchester’s and Honorary Consultant Rheumatologist at , had the original idea for the experiment. He said: “This project is all about getting people involved in the scientific process.

“We don’t have the answers for this important question, but by getting large numbers of people to look at the results, we hope that someone will have a flash of insight that could lead to a breakthrough.”

Anyone can take part in the study by visiting and looking at the data which can be displayed as symptom and weather landscapes. People can explore reported symptoms such as pain intensity alongside weather parameters such as barometric pressure using graphics developed by in New York. They can then enter their hypotheses about any relationships they spot (or not).

Suggestions will be assessed by the research team and may form part of the final results of the study next year. The team will be highlighting some of the hypotheses it receives on the website and social media channels.

Dr Dixon said: “The project got global attention when it was launched and this led to us receiving dozens of possible explanations from the public and seeing hundreds more on social media. Now people have a chance to have a good look at the study data and give us their theories about if and how the weather affects pain.”

Cloudy with a Chance of Pain is the world's first smartphone-based study to investigate the association between pain and the weather. The study is being carried out during 2016 using a smartphone platform called which people will use to record how they’re feeling, whilst local weather data is automatically collected using the phone's GPS.

Anyone in the UK with arthritis or other chronic pain and aged 17 or over can take part. All participants need is a smartphone. Once the project ends in January 2017, the research team will also carry out a formal analysis and hope to use the information for generating pain forecasts, allowing people to plan their weekly activities.

Dr Dixon added: “There are many variables at work here. For example, does temperature affect people’s pain? And if so, is it an increase or decrease? The rate of increase or the absolute value? And is it instantaneous or is there a lag of a few days?

“These are all questions that need to be answered and we need as many people to take part as possible.”

The University of Manchester will be showcasing the citizen science project at Cheltenham Science Festival on Saturday 11 June, and at 91ֱ�� Day on Sunday 19 June.

Visit to take part.

91ֱ�� researchers and  (PRUK) have published research exhibiting the valued role pharmacists can play in supporting young people with juvenile arthritis to self-manage their condition.

Researchers, including The University of Manchester’s Dr Janet, explored the role of pharmacy for young people with long term conditions (LTCs) through the exemplar of juvenile arthritis. It builds on an earlier PRUK funded project (Arthriting) exploring young people and parents’ experiences of using medication to treat juvenile arthritis by bringing together pharmacists and rheumatology staff to explore how pharmacy might develop and promote a vision for the care of young people with long term conditions.

Although 59 per cent of young people with LTCs take medication, there is limited evidence around young people’s experiences and use of pharmacy services. The study demonstrated the potential for pharmacists to support young people in better self-managing their condition. Establishing positive relationships is at the heart of the results – pharmacists building trust and rapport with young people, better communication between hospital and community pharmacists, and meaningful integration of pharmacists into multidisciplinary clinical teams.

Rheumatology lead, who also works at the , said: “The previous Arthriting project showed us that young people with arthritis were largely unaware of the pharmacist’s skills and relevance to their medicine-related needs. Parents generally go in to collect prescriptions alone, and opportunities to build relationships with a very accessible healthcare professional are missed.”

The project lead, pharmacist Dr Nicola Gray, said that: “We know that young people find it difficult to access health services and that young people with arthritis are largely unaware of the pharmacist’s skills and relevance to their medicine-related needs. This new project shows that pharmacists have the potential to help young people to build general healthcare skills, and to respond to their queries and concerns about their medication.”

Miss Lamis Mullgrave, one of the original Arthriters (youth participant) and advisor to the project, said: “From my own experiences and from speaking to other young people, it is clear there is not enough information out there to promote the role of pharmacists, or awareness of the pharmacy services currently available.

“It is important for young people and their families to have easy, accessible support with regards to medicines, and help with managing them, so to highlight this issue I believe is important as a means of improving healthcare for young people, [and] to encourage building relationships with pharmacists to support them in managing not only their medicines, but their health. I feel the findings from this project are of great value, and we should seek to implement these recommendations to improve health services for not only young people, but for service users of all ages.”

Glucocorticoid (or steroid) therapy, prescribed to around half of patients with rheumatoid arthritis, is a known risk factor for developing diabetes. A study from The University of Manchester has found how the risk of diabetes increases in relation to the dosage, duration and timing of steroids.

In a paper published in the journal Arthritis and Rheumatology, the researchers looked at the records of more than 20,000 patients with rheumatoid arthritis in the UK and compared rates of new-onset diabetes in those who were prescribed glucocorticoids to those who didn’t receive glucocorticoids.

They found that glucocorticoids were associated with one new case of diabetes for every 150-200 people treated per year. However, within this group, risk was affected by the dose only in the most recent six months. Each increase of 5mg prednisolone per day carried a 25-30 percent increase in diabetes, although a dose of less than 5mg wasn’t associated with any measurable risk of diabetes compared to no treatment.

Dr Will Dixon, Director of at The University of Manchester and Honorary Consultant Rheumatologist at , led the study. He said: “Doctors treating people with arthritis have to make a decision how best to prescribe glucocorticoids by balancing the benefits against the risks. However, until now, no studies have considered how the risk changes with the dose and duration of treatment.

“This research provides important evidence for doctors to make this decision.”

As well as the 21,962 patients from the UK database, the research team also checked their results against a further 12,657 records held in the USA. Results also took into account patients’ BMI and smoking status, as well as their disease severity.

The research does not advocate that people stop using glucocorticoids as they have been used effectively since 1948 to treat flare-ups in joint pain and for longer periods at a low dose to help people who don’t respond to other treatments.

Mrs Stones is a patient with rheumatic diseases that have required steroid therapy for several decades. In this time, she has developed multiple steroid-related side effects including fractures and diabetes. She said: “It is important that health professionals communicate clearly, and transparently with patients, so that decisions can be made together. Understanding the risk of long-term steroids needs to be better communicated, as they can have life-long implications on quality of life.”

Dr Dixon said: “This research shows that low doses of steroids (below 5mg/ day) do not increase the risk of diabetes. However, there is an increased risk of acquiring diabetes for people who use them for long periods or at high doses which can now be quantified.”

The paper, ‘’, was published in the journal Arthritis and Rheumatology.

DOI: 10.1002/art.39537

Research from The University of Manchester has found a shortfall in the uptake of influenza and pneumococcal vaccinations among those diagnosed with rheumatoid arthritis (RA), potentially increasing their infection risk.

The team from looked at data from over 15,000 patients diagnosed with the disease who were being treated with certain types of immunosuppressive drugs, and found that one in five patients received no influenza vaccinations and one in two patients received no pneumonia vaccine over a five year follow-up period.

Patients with rheumatoid arthritis have double the normal risk of infection, due to a range of factors, compared to the rest of the population. Guidelines recommend that vaccinations should be used to protect against certain infections, such as influenza and pneumonia.

, who led the study, said: “There is no national data on vaccination uptake broken down in a way that allows us to pull out those with RA. Only one study in the US has looked at whether patients with rheumatic diseases are being vaccinated prior to starting immunosuppressive therapy.”

This large study used information from electronic patient records to assess the take-up of the two vaccines. It looked at 15,724 patients diagnosed with RA between 2000 and 2013.

The group found that those who were younger, who did not meet another clinical risk category, and who visited their GP less often were least likely to be vaccinated.

, a GP who was also part of the study team, added: “Guidance on influenza and pneumococcal vaccination for RA patients is unclear, and payment to carry it out in primary care is variable.

“In future it may be beneficial for rheumatologists to provide GPs with specific advice about appropriate vaccination for individual patients, or to consider administering the vaccinations themselves in their own clinics – either way, both approaches should be adequately funded.”

Richard Francis, head of research liaison and evaluation at , said: “Around 400,000 people in the UK live with the excruciating pain of rheumatoid arthritis. The impact of rheumatoid arthritis and the drugs used to treat the condition on the ability to fight infection is significant, and this study underscores the importance of vaccination in helping prevent the impact of influenza and other infections.”

Paper entitled ‘’, published in the journal PLoS One

University of Manchester-led research has found new evidence to suggest that, not only is smoking associated with earlier deaths in those with rheumatoid arthritis, but also those who stop smoking dramatically reduce their risk of earlier death, as published in Arthritis Care and Research journal.

Although there is a lot of evidence to show the association between smoking and increased risk of early death in the general population, researchers at were keen to find out the relationship between stopping smoking and subsequent mortality in patients with rheumatoid arthritis.

It has been previously shown that smoking plays a role in the development of rheumatoid arthritis, and so the prevalence of smoking is higher in these patients than in the general population. Those with rheumatoid arthritis also have an increased risk of dying earlier due to developing other health conditions such as cardiovascular disease, cancer, severe infection and respiratory diseases.

The research, led by Rebecca Joseph, Research Assistant at at The University of Manchester, analysed anonymised patient information from an electronic UK-based GP database, which included information on hospital admissions and death certificates.

Researchers found that the risk of death was almost two times higher in patients who smoked compared to those who never smoked, whilst the risk of death for former smokers was similar to that for never smokers. Furthermore in the patients who stopped smoking, the risk of death fell for each additional year they had given up.

, Professor of Rheumatology and Musculoskeletal Epidemiology at The University of Manchester explained: “This research provides important evidence that the risk of early death starts to decline in patients who stop smoking, and continues year on year.

“We hope that this research can be used by public health professionals and rheumatologists to help more people quit smoking and reduce premature deaths, particularly for newly diagnosed patients with rheumatoid arthritis.”

Commenting on the study which was supported by the charity , Stephen Simpson, Director of Research and Programmes said: “Rheumatoid arthritis is a debilitating and painful condition affecting over 400,000 people in the UK, it can begin at any age and is unpredictable - one day you can feel fine and the next day be confined to bed, unable to get up to dress, even go to the toiled unaided.

“As a charity, we are committed to preventing, transforming and curing arthritis and musculoskeletal diseases, and this research shows that cutting out smoking is one intervention which can help this condition from developing.”

The paper, ‘’ was published in the journal Arthritis Care and Research.

doi: 10.1002/acr.22882

It’s a mystery that’s perplexed people for over 2,000 years, but now University of Manchester scientists are on the verge of working out if the weather affects pain in people with arthritis and other conditions, all thanks to the British public and their smartphones.

, which launches today (26 January) is the world's first smartphone-based study to investigate the association between pain and the weather. The study will be carried out during 2016 using a smartphone platform called which people will use to record how they’re feeling, whilst local weather data is automatically collected using the phone's GPS.

Anyone in the UK with arthritis or chronic pain and aged over 17 can take part. All participants need is a smartphone.

Click to download the app and take part.

, Director of The University of Manchester’s and Honorary Consultant Rheumatologist at , came up with the idea. He said: “This question has been around for more than 2,000 years, but it’s only now with widespread modern technology that we have the ability to answer it.

“And we’re not just inviting people to submit data – we want their ideas about the association between weather and pain too. We will be running a big citizen science experiment where anyone can explore the data and try and spot patterns and relationships in the data. We’ll gather ideas and theories from everyone to come up the best possible conclusion.”

The University of Manchester research is supported by , uMotif in London, and h in New York. It is being carried out in association with the University’s .

Those who choose to use the uMotif app will record their symptoms each day, which will be tied into automatically collected local weather information. Even people who don’t have pain will be able to participate by browsing through the data and submitting their own ideas.

Once the project ends in January 2017, the research team will also carry out a formal analysis and hope to use the information for generating pain forecasts, allowing people to plan their weekly activities.

Stephen Simpson, Director of Research & Programmes at Arthritis Research UK said: “Many people with arthritis believe that changes in the weather affect the level of pain they experience, however there is currently no scientific evidence to support this relationship.

“This exciting study will for the first time enable us to investigate the link between pain and the weather. We’re delighted to support this project and we hope that the use of the uMotif app will help encourage a wide group of participants to take part, both in terms of submitting their data but also examining the results themselves to help our scientists reach a conclusion.”

Dr Dixon added: “People taking part in this study will be helping to answer a question that even the father of modern medicine, Hippocrates, couldn’t resolve, and which hasn’t been resolved since. That’s what epidemiology is all about – drawing patterns and inspiration from large groups of people to provide insights which we couldn’t otherwise achieve –this time with the help of their smartphones.”

Follow the project on Twitter

Click to download the app and take part.

A new collection of artworks on display in Salford (21-24 January) has been inspired by x-rays taken from Salford’s coal-miners in the 1950s which helped establish a world-wide method of classifying the severity of osteoarthritis.

worked as artist in residence at The University of Manchester’s during 2015 and was inspired by the x-ray archive held in the Centre.

Between 1950-1952, the University’s Dr John Lawrence studied the relationship between occupation and arthritis. He collected x-rays from local miners (the majority from Salford) and his study found that miners had more degenerative spinal disease.

The x-rays underpinned the ‘Kellgren & Lawrence’ classification system for osteoarthritis, still in worldwide use today.

Taking Dr Lawrence’s x-rays as her starting point, Nicola has created a new body of work that encompasses sculpture, collage and photography. It is primarily concerned with the idea of illumination: from the lightbox needed to read x-rays and the flickering of the miner’s lamp, to the lightbulb moments that inspire scientists and artists alike. 

Through interviews and workshops, she has also engaged with local miners and current arthritis patients to create a mysterious and beautiful exhibition.

She said: “Speaking to miners has been like getting the x-rays to talk to me – it’s really bought them to life. I have learned so much about what it was like to work in such a tough job. The miners’ memories have been really inspiring.”

Dr Will Dixon is Director of the Arthritis Research UK Centre for Epidemiology and an Honorary Consultant Rheumatologist at . He said: “Nicola’s inspirational artwork encapsulates the science of epidemiology: the study of the occurrence and determinants of disease in populations.

“Drawing on the strong heritage of arthritis research in 91ֱ�� and Salford, it captures the insight derived from populations, as well as highlighting the importance of individuals. It is a truly wonderful celebration of this important archive.” 

Opening night                      6-8pm, 21st Jan 2016

Exhibition continues           12-6pm, 22nd – 24th Jan 2016

Artist’s talk                 1-2pm, 23rd Jan 2016

Audience       This event is FREE, suitable for all ages and open to anyone with an interest in science, medicine, local history, mining, arthritis or art

Please note: the exhibition floor has no disabled access

New research from The University of Manchester and the Babraham Institute has revealed how gaps between genes interact to influence the risk of acquiring diseases such as arthritis and type 1 diabetes.

Writing in Nature Communications, the scientists show gap regions within the folds of DNA that have a crucial effect on turning genes on and controlling their expression, actually physically interact with genes not previously thought to be important in disease.  Many of these genes are now thought to increase the risk of people developing diseases such as arthritis, psoriasis and type 1 diabetes.

Lead researcher from The University of Manchester said: “It used to be the case that researchers would seek to identify a gene which caused a particular disease by a ‘nearest gene’ approach, to the gap regions.
 

“The reality is much more complex than that.  Not only do the gaps between genes have an effect but, as we show in the new study, the gaps don’t necessarily affect the nearest gene – they can work over longer distances to turn distant genes on or off.”

This process is caused by the folding of the two metre DNA to make it fit within a cell. This folding, brings gap regions close to the ‘more important’ regions, and therefore controls the levels of genes. In certain parts of the folded DNA, regions that increase risk to different diseases can ‘meet’ at the same gene.

The findings also open up the possibility that some genes may be increasing the risk of more than one disease, depending on how they are regulated by the gaps and from where in the DNA structure.  This knowledge could lead to greater understanding of the diseases and insights into potential treatments. 

The next steps in the research are to identify more of these complex interactions and in different types of cell in order to build a more complete picture of how genes and gaps interact to increase disease risk. 

Dr Eyre added: “This research shows just how complicated the interactions within our cells are – much more so than was previously thought.  However, by gaining a better understanding of this process we open up many more possibilities for research into cures and treatments in the years ahead.”

The research was funded through and a Fellowship and has had support from The National Institute for Health Research (NIHR) . Researchers from the University of Cambridge and the Babraham Institute also contributed to the work.

The paper, ‘Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci’ was published in the journal . DOI:

Scientists at The University of Manchester have shown for the first time that the numbers of opiate receptors in the brain increases to combat severe pain in arthritis sufferers. 

Chronic pain – pain which lasts for more than six months – is a real problem for many people with approximately 46% of the UK population estimated to suffer from it (comprising 20% of consultations in general practice).   However, some people seem to cope better than others with pain, and knowing more about how these coping mechanisms work might help to develop new ways of treating this distressing symptom.

It has been known for a long time that we have receptors in our brains that respond to natural painkilling opiates such as endorphins, but the researchers in 91ֱ�� have now shown that these receptors increase in number to help cope with long-term, severe pain.

By applying heat to the skin using a laser stimulator, Dr Christopher Brown and his colleagues showed that the more opiate receptors there are in the brain, the higher the ability to withstand the pain.

The study used Positron Emission Tomography (PET) imaging on 17 patients with arthritis and nine healthy controls to show the spread of the opioid receptors.

This suggests that the increase in opiate receptors in the brain is an adaptive response to chronic pain, allowing people to deal with it more easily.

Dr Brown said: “As far as we are aware, this is the first time that these changes have been associated with increased resilience to pain and shown to be adaptive. 

“Although the mechanisms of these adaptive changes are unknown, if we can understand how we can enhance them, we may find ways of naturally increasing resilience to pain without the side effects associated with many pain killing drugs.”

is the director of the 91ֱ�� Pain Consortium which is focused on improving the understanding and treatment of chronic pain. He said: “This is very exciting because it changes the way we think about chronic pain. 

“There is generally a rather negative and fatalistic view of chronic pain.  This study shows that although the group as a whole are more physiologically vulnerable, the whole pain system is very flexible and that individuals can adaptively upregulate their resilience to pain.

“It may be that some simple interventions can further enhance this natural process, and designing smart molecules or simple non-drug interventions to do a similar thing is potentially attractive.”

Val Derbyshire, a patient with arthritis said: “As a patient who suffers chronic pain from osteoarthritis, I am extremely interested in this research.  I feel I have developed coping mechanisms to deal with my pain over the years, yet still have to take opioid medication to relieve my symptoms. 

“The fact that this medication has to be increased from time to time concerns me greatly, due to the addictive nature of these drugs. The notion of enhancing the natural opiates in the brain, such as endorphins, as a response to pain, seems to me to be infinitely preferable to long term medication with opiate drugs. 

“Anything that can reduce reliance on strong medication must be worth pursuing.”

Professor of Cognitive Neuroscience at the University, said: “Receptor imaging is challenging and requires the co-ordination of a large team to collect and analyse the images.   We are very lucky to have this technique in 91ֱ��. There are very few places in the world where this study could have been done.”

The paper, ‘’, featured in , published by Wolters Kluwer. doi: 10.1097/j.pain.0000000000000299

The research was funded by .