Focus on Nottingham

Published on 01 July 2010
Source: Arthritis Today

Skeleton of pain

Pain is the number one concern for patients with arthritis, yet there have been too few advances in how to manage it. The new Arthritis Research UK Pain Centre at The University of Nottingham aims to achieve a greater understanding of pain – and to come up with more effective ways of dealing with it. Jane Tadman reports. 

Millions of people with arthritis in the UK have to live with chronic pain every day, pain which blights their lives and often makes it difficult to live normally.

Pain-relieving drugs such as paracetamol, anti-inflammatories and opiates all have a part to play, but none are ideal, either lacking effectiveness or bringing with them the risk of unpalatable and sometimes dangerous side-effects.

A new approach is obviously much needed and a team of researchers at the new Arthritis Research UK Pain Centre in Nottingham believe they have enough joint expertise to make some real progress over the next five years.

Their aims are ambitious, but the team are confident they are achievable. Not only do they want to develop a better understanding of how people experience pain, but to also use that knowledge to fully understand the biological basis of pain, to find out which of the existing painkilling drugs work the best in individual patients, and to work towards developing completely new drugs. And by studying the evidence from imaging techniques such as MRI, the team hope to find out how an individual’s way of processing pain signals may explain why their experience of pain may not necessarily match the severity of their joint damage seen on x-ray.

Experts from the fields of rheumatology, neuro-imaging, psychology,
neuropharmacology, neurosciences and orthopaedic surgery will all play a big part in realising the ambitions of the centre, funded over five years by £2.5m from Arthritis Research UK and a further £3m from The University of Nottingham. 

Three distinct approaches

The team are taking three distinct but linked approaches to the problem, using osteoarthritis of the knee as their model.

They plan to:

Look at pain from a social context;finding out from patients their own understanding of what pain is, and what they expect from treatment.
Investigate closely two forms of pain mechanisms: the role of peripheral pain (pain that comes from the nerves in the joints) and central pain (the way that the brain responds to and processes chronic pain) and try to produce new compounds that target these pain pathways.
Run clinical trials aimed at testing existing drug therapies, and any new painkillers that may be produced over the next five years.

The team are taking three distinct but linked approaches to the problem, using osteoarthritis of the knee as their model. They plan to: Look at pain from a social context;finding out from patients their own understanding of what pain is, and what they expect from treatment. Investigate closely two forms of pain mechanisms: the role of peripheral pain (pain that comes from the nerves in the joints) and central pain (the way that the brain responds to and processes chronic pain) and try to produce new compounds that target these pain pathways. Run clinical trials aimed at testing existing drug therapies, and any new painkillers that may be produced over the next five years.

Centre director Dr David Walsh, associate professor in rheumatology, says that while the interplay of various factors that cause pain are already known, our understanding of how all those factors contribute to the final experience of pain is incomplete, which he describes as “our great challenge.” He adds: “Within five years we will have a much better understanding of the mechanisms behind pain, will have piloted trials looking at targeting the effectiveness of existing drugs, and played a big part in the development of new painkilling drugs.” 
                                                                                                                                                    So what will the leading members of the research team be contributing to the work of the centre?

Nadina Lincoln, professor of clinical psychology

Professor Lincoln will be running interviews with patients with osteoarthritis and compiling questionnaires in order to understand more about the psychological side of pain. “We will be asking people about their pain, and their experiences of treatment. The extent to which treatment is consistent with their beliefs will have an effect on their response to treatment. For example if a patient thinks exercise is harmful to their joints, they may not exercise, even if it is recommended to them.”

Victoria Chapman, professor in neuropharmacology, and Sara Kelly, lecturer in neuroscience  

Professor Vicky Chapman and Dr Sara Kelly

Professor Chapman and Dr Kelly are interested in the mechanisms underlying pain in the osteoarthritic joint, and will be using models of osteoarthritis to investigate changes within the joint and the peripheral nervous system, spinal cord and brain. Joints and bones (although not cartilage) have a high number of nerve endings, and there is evidence that the nerve fibres and the central nervous system become sensitised in arthritis. Understanding the mechanisms that lead to this sensitisation will help the identification of novel targets for drugs which can block these changes and decrease pain responses.

Professor Chapman and Dr Kelly are interested in the mechanisms underlying pain in the osteoarthritic joint, and will be using models of osteoarthritis to investigate changes within the joint and the peripheral nervous system, spinal cord and brain. Joints and bones (although not cartilage) have a high number of nerve endings, and there is evidence that the nerve fibres and the central nervous system become sensitised in arthritis. Understanding the mechanisms that lead to this sensitisation will help the identification of novel targets for drugs which can block these changes and decrease pain responses.

 

Dorothee Auer, professor of neuroimaging

Professor Auer aims to gain a greater understanding of central pain and pain relief by looking at the brain’s signature of spontaneous pain and responses to induced pain and acute pain relief. Using functional magnetic resonance (fMRI), the activation in different parts of the brain will be compared to patients’ pain perception and expectation. This will allow them to disentangle the processing of painful stimuli from adaptive brain processes and their influence on the effectiveness of pain relief.

"We all have different personalities, different ways to respond and deal with pain and different experiences of pain that may need to be taken into account for best treatment effect. Our study approach is to investigate the neurobiological underpinnings of such individual pain and treatment response characteristics. Understanding how a person’s brain is likely to adapt to pain stimuli will inform the development and assessment of individual pharmacological and non pharmacological treatment."

Brigitte Scammell, professor of orthopaedic science 

Brigitte ScammellProfessor Scammell is a surgeon specialising in lower limb surgery. She is particularly interested in possible sensitisation of the brain to pain caused by arthritis, particularly as 15 per cent of knee replacement patients still suffer pain after surgery. With Professor Auer, she will study fMRI images of the brains of pre- and post-operative knee replacement patients to see if the brain processes pain differently before surgery compared to after the operation.

Mike Doherty, professor of rheumatology, and Weiya Zhang, associate professor of musculoskeletal epidemiology

Professors Doherty and Zhang will use their extensive experience of running clinical trials into osteoarthritis to run an ambitious clinical trial Weiya Zhang(yet to be funded) which will test several existing treatments – paracetamol, topical ibuprofen, codeine and corticosteroid injections in people with knee osteoarthritis. Explains Mike Doherty: “We will give people four different treatments for each in a random sequence plus a placebo, to measure the response and to also find out how much the placebo effect varies from person to person, and gather robust data on the common treatments which is not currently available.” Other less commonly used drugs such as gabapentin, and any new compounds developed during the course of the five-year research programme, may also be trialled.
Meanwhile, an evidence-based osteoarthritis research database (eBOARD) will be developed to assess the clinical effectiveness and costeffectiveness of all available therapies in the management of pain due to osteoarthritis. This will ensure the translation from research evidence to clinical practice and the optimisation of these therapies.

The Arthritis Research UK National Pain Centre at The University of Nottingham was officially opened on July 1.