The Pain Relief Foundation has long supported the work of the Pain Research Institute and part funds both the post of Professor of Pain Science and Clinical Senior Lecturer in Pain Medicine at the University of Liverpool.
In addition funding in the form of annual grants is awarded to individuals working both within the Institute and elsewhere on chronic pain research. Grants are awarded each year based on the quality of applications.
PhD Studentship to Dr Liz Cordingly – University of Manchester
One and the same?”: An in-depth investigation into the complexities of pain experiences of children and young people with inflammatory and non-inflammatory conditions
Chronic pain is experienced by up to 40% of children and young people and can have a major impact on function and wellbeing. Pain may last longer than expected through complex biological and psychological processes, many of which are not well understood. Treatment approaches tend to be based on whether the individual is considered to have either ‘inflammatory’ or ‘non-inflammatory’ pain. ‘Inflammatory’ pain is seen as a symptom of an underlying condition (such as juvenile arthritis) and non-inflammatory pain is often used to describe pain where there is no other medical cause. We know very little about whether children or young people experience pain differently depending on the diagnosis, nor do we know about the impact that each of these diagnoses have on individuals, such as the frequency or severity of pain episodes between these groups. This is important to investigate given that each of these diagnoses are managed differently, in ways which may not be appropriate based upon our limited understanding of how pain works within these conditions.
This PhD studentship will be the first project to explore this important ‘pain type’ distinction, both through qualitative and quantitative methods. The candidate will use new and novel data collection tools, alongside well-established methods such as interviews. As part of our team’s ongoing research, we have developed an iPad application called My Pain Tracker (MPT), which captures multiple features of pain. It is preferred by young people, because rather than simply rating their pain severity from 1-10, they can communicate more about their pain experiences, such as its location, quality, intensity, emotional impact or degree of interference with normal activities. MPT now allows us to be able to address more sophisticated research questions than has previously been possible and this studentship will be at the forefront of this exciting field.
A research grant to Dr Stephanie Koch – University College London
Identifying spinal circuits in chronic widespread pain
Unrestricted widespread pain is a hallmark of chronic pain, and is a major therapeutic challenge for clinicians, in part due to the unpredictable nature of spreading pain across multiple body regions. The central nervous system learns to refine its response to pain over the course of early life: infants show whole body responses to painful stimuli, much as is seen in chronic widespread pain. These pain responses subsequently become refined over adulthood, leading to restricted pain responses seen in the healthy adult. Studying the development of pain circuits from the unrefined responses seen in the infant to refined pain responses seen in the adult therefore provides a novel framework to understanding how chronic pain leads to widespread pain responses. This programme will use the developmental maturation of sensory networks to investigate how circuits naturally adapt to control pain, and so how to correct these circuits when they are maladapted in the case of chronic widespread pain. Using cutting edge behavioural analyses, viral tracing, and state-of-the-art genetic technology, I will determine the neurochemical identity of these circuits thus providing potential new pharmacological targets for future chronic widespread pain therapies.
A Research grant to Dr Geoff Woods – Cambridge University
Novel long-acting analgesic for chronic pain’A Pilot project seeking genetic predispositions to fibromyalgia.
The aim of this project is to find out if a persons’ genes influences whether they develop fibromyalgia. Fibromyalgia is a cause of widespread pain and stiffness and fatigue, which usually disrupts sleep. The problems with fibromyalgia are that, it is common, we do not understand the cause, and medical treatments often do not work (and can cause
If we could understand why the condition occurs, then we may be able to,
- Diagnose it more quickly and accurately.
- Be able to tell who will recover quickly (and does not need treatment), and who will get the features long term.
- Know which medicines/therapies to try, and which to avoid.
We want to look for genetic changes that make a person more likely to get fibromyalgia. To do this,
- We have collected two groups of people with severe fibromyalgia (80 altogether),
- From each person we will use a blood sample to look at the DNA of all of their genes.
- Throughout all of our genes are changes that vary from person to person, and most are probably harmless (we ignore these), but some could alter the way a gene works.
- Looking at all 80 people’s results together for only changes that could alter the way genes work we can see if any of the gene changes are much more common than expected.
- If we find these, we will then use (mostly) internet tools to determine which changes are real and existing.
- (we have successfully used this approach twice before in pain conditions).
This is a first step. If it is successful, it will point us towards the genes and processes that cause fibromyalgia, and hopefully also to treatments.
A Research grant to Dr Nick Fallon – Liverpool University
Investigating the relationship between central& peripheral pathophysiology in fibromyalgia symdrome – pilot neuroimaging study.
Fibromyalgia syndrome is a chronic pain disorder which affects 1 in 20 people in the UK. It has a severe impact on quality of life of individuals, and represents a high cost to our NHS. The causes of fibromyalgia are not fully understood and current treatments are often deemed unsatisfactory. Our previous research using brain imaging revealed differences in brain structure and function which contribute to pain in fibromyalgia . However, evidence from our team and others indicates that nerves located throughout the body (peripheral nerves) also play an important role. We believe that both of these mechanisms work together to shape patient experience, This project aims to investigate whether brain and peripheral mechanisms are related to each other. As a pilot study, this represents the first research to measure relevant brain and peripheral nerve activity in the same group.
Our team is made up of experts in brain and peripheral nerve imaging. We have unique access to a suitable group of 77 people with fibromyalgia who are participating in a project to investigate their peripheral nerve function. We propose to utilise a sub-group of these patients who will volunteer for an additional brain scan at the University of Liverpool. We will consider whether patients find this research to be acceptable and perform a preliminary analysis of the relationship between brain and peripheral nerve function. We anticipate that our study will highlight, for the first time, the existence of a positive relationship between these two mechanisms. This will directly contribute to the development of research which investigates the balance of this mechanisms in relation to patient symptoms or treatment response. Our overarching aim is to eventually develop clinical approaches which can categorise individuals to improve diagnosis for fibromyalgia, or to target individualised treatment plans which improve the lives of patients.
A Research grant to Dr Andrew Marshall – The Walton Centre NHSFT, Liverpool
Reversal of EEG theta band rhythm as an objective measure of efficacy of spinal cord stimulation in chronic neuropathic pain – a pilot study.
Chronic neuropathic pain is a very common condition. Some patients suffering this condition are refractory to medical management and are therefore considered for implantation of spinal cord stimulator. Unfortunately, spinal cord stimulation only works for 60-70% patients. Currently, these patients are identified by a trial of spinal cord stimulation and subjective pain relief is used for decision making. This is no always accurate.
Recent studies have shown that brain activity mapping in the form of electroencephalography shows dominance of slow (theta) waves in patients with chronic neuropathic pain. Reversal of this pattern to normal is seen with effective spinal cord stimulation.
In this study we aim to see if the reversal of theta activity could be used as an objective marker of effective spinal cord stimulation. To do this, we aim to record EEG before and during trial and after 6 months of implantation of SCS. The obtained results shall be compared against subjective pain relief to assess the validity of EEG as an objective test. Also there are three main forms of SCS and each is known to affect EEG in specific manner. As a secondary aim of this study we seek to assess if EEG can be used to identify which stimulation type is best suited to a given patient. This shall be achieved by comparing the patient’s baseline EEG with EEG obtained during stimulation with each type of SCS during trial period and comparison will be made to respective subjective scores.
A Research grant to Dr Andreas Goebel – Liverpool University
Autoimmunity informed phenotyping in chronic non specific low back pain sufferers.
Non-specific low back pain (NsLBP) is a common painful condition and refers to the experience of back pain without an identified injury causing it. Despite its common occurrence, we do not fully understand the causes and risk factors and many people suffer from severe, disabling symptoms without effective management.
Recent research from our group has identified the importance of immune factors in the chronic painful conditions complex regional pain syndrome (CRPS) and fibromyalgia. These conditions are associated with severe pain on light touch pressure and local skin signs such as increased sweating, or with widespread pain, respectively.
Some patients with severe NsLBP present with similar skin signs to CRPS, and NsLBP is a risk factor for the development of fibromyalgia. We wish to find out whether sub-groups of NsLBP sufferers may have similar skin immune factors as CRPS and if sufferers can be identified early as being at particularly high risk for the development of fibromyalgia this study will also provide blood samples for later analysis into immune factors,
We will identify 100 patients through back pain physiotherapy clinics at the NHS Walton Medical Centre and Aintree University Hospital and invite them for a single visit for clinical assessment and blood donation. Participants with severe skin symptoms will be asked to return for a re-assessment scheduled at a time of maximal pain flare. In a one-year follow-up telephone consultation we will then assess all patients for the development of widespread pain and will invite those that have developed widespread pain and will invite those that have developed widespread pain (about 1/5) for a repeat assessment visit.
We expect that this study will allow us for the first time to identify subgroups of NsLBP with similarities to CRPS or fibromyalgia, opening new avenues for their future treatment.
A Research Grant to Dr Nick Fallon – University Liverpool
Impact of COVID-19 related lockdown and isolation on chronic pain experience.
Myself and local colleagues (Dr Christopher Brown, Dr Andrej Stancak, Dr Charlotte Krahe, Miss Eleanor Brian, Dr Hannah Twiddy, Dr Bernhard Frank & Prof. Turo Nurmikko) have initiated some online research to consider the impact of UK responses to the COVID-19 on people living with chronic pain. We believe that the implementation of lockdown measures, social distancing and isolation could exacerbate pain and other symptoms and adversely affect the lives of those living with chronic pain. We hope to capture and understand this using a longitudinal online study that will follow patients from lockdown for at least the next 3 months with an option to follow-up for a longer period.
We are now approaching our study capacity (total 300) for the funding we have available. However, we would really like to continue and collect more patients during this critical period. The data we have accumulated so far is very encouraging (see attached preliminary analysis document). However, greater numbers would allow us to perform more complex analyses in future, e.g., to consider whether particular types of chronic pain patients are more affected than others and require more help and support at this time. This would help us to turn the findings into something that we can utilise to improve the care provision for UK chronic pain patients.
MSc Health Psychology Student Liverpool John Moores University.
A qualitative study on opioids in the management of chronic pain
A PhD Studentship to Dr Abbie Jordan
Exploring resilience in adolescents with chronic pain and their parents.
Research studies have shown us that chronic pain has a harmful effect on the lives of many young people, resulting in emotional distress, physical disability and changed relationships. However, some young people report feeling more able to manage the challenges posed by living with chronic pain than others do, even when levels of pain and disability are similar. Researchers understand this ability to ‘bounce back’ from life challenges and difficulties as ‘resilience’. Yet, we know very little about how resilience is understood and experienced by young people living with chronic pain and their parents.
Through a series of related studies, this studentship will provide a detailed account of how young people with chronic pain and parents understand ‘resilience’, how they experience resilience, and its impact on their lives. Study one will review the evidence surrounding chronic pain in young people and resilience. Using a technique called Q-sort, the second study will ask 20 young people with chronic pain, 20 parents and 20 healthcare professionals to rank statements about resilience and pain. This will help us to understand how different groups think about resilience. Study three will collect questionnaire data over three-time points from 100 young people with chronic pain (10-24 years) and parents regarding their pain-related disability, resilience and well-being. In study four, 20 pairs of young people and parents will tell us about their everyday experiences of resilience by completing daily online diaries for two weeks.
Study findings will provide important insights into how young people and parents understand and experience resilience over time. This new knowledge will inform treatment of chronic pain in young people by enabling the development of resilience-focused treatments, which will provide tools to young people with chronic pain, and parents to enable them to better manage their pain and its impact on their lives.
An investigation into the meaning and differential impact of resilience among adolescents with chronic pain and their parents
A research grant to Dr Francis O’Neil, University Liverpool
‘Corneal Confocal Microscopy in stratifying and tracking Small nerve fibre neuropathy in Burning Mouth Syndrome.
Burning mouth syndrome (BMS) is a painful burning sensation which can affect the tongue, palate or lining of the cheeks. It can be difficult to treat with sufferers being affected long term, causing significant distress.
BMS patients may be divided into subgroups based on their response to either lingual nerve block or blink reflex testing. These methods show patients can be sub-grouped into those that have a predominantly peripheral nerve involvement and those that have a predominantly central nervous system involvement. This is important because some BMS patients may respond better to peripherally acting drugs and others to those acting centrally.
We have shown recently that a new test called Corneal Confocal Microscopy (CCM), which looks
at the surface of the eye that is exclusively innervated by small fibre nerves, can detect small nerve fibre changes in some BMS patients. The numbers were small in our previous study but if we can show that CCM can differentiate subgroups of BMS patients then this rapid, non-invasive method would be useful in guiding personalized treatment options for patients. It would also be useful in research to track small nerve fibre changes in disease progression or response to treatment.
We propose to compare CCM data in healthy controls and BMS patients that have been subgrouped by their response to lingual nerve block and blink reflex testing. We will compare the CCM data to small nerve fibre counts in tongue biopsy samples from the same patients to ensure the findings are similar. Furthermore, we will look at changes in the density of a type of immune cell called Langerhans cells in these biopsies as an increase in Langerhans cell density was detected in our CCM study and this would help us confirm if these changes also occur in the oral mucosa.
A research grant to Dr Franzika Denk, Kings College, London
Cerebrospinal fluid – a window into how our central nervous system processes pain.
Current research suggests that chronic pain frequently results from miscommunication between our immune and nervous systems. However, evidence for this interaction in the central nervous system (CNS) comes mainly from experiments in models , since it is difficult to study with imaging. One way to overcome this challenge is to use the human cerebrospinal fluid (CSF). It contains number of immune cell, as well as the proteins they and the CNS release.
Together with collaborators at the Karolinska Institute, we have optimized the latest technologies to study CSF, which we now want to apply to study patients who are undergoing high frequency spinal cord stimulation as a treatment for chronic neuropathic pain.
CSF will be drawn when stimulators are implanted. We want to (1) isolate the different immune cells that are in CSF using a cell-sorting technology called ‘FACS’; (2)Check wihich genes they express; (3) study the proteins that are in the CSF solution. The nature of the pain the patients experience will be well- characterised and include measure of fatigue and quality of life.
We have personnel employed who could dedicate time to this project, but require consumables funding. We would like to answer the following questions.
(1) Is what is true in models also true in people: immune cells release substances that make CNS neurons hyper-sensitive and contribute to chronic pain?
(2) Can we use this information to group patients to identify those whose pain is entirely driven by the CNS compared to those whose pain is still driven by nerves out in the body.
(3) Can we use this information to predict outcomes in our clinical trials?Not all patients respond well to surgery and it would be useful to have a way to save those who are unlikely to benefit from a painful operation.
A research grant to Dr Bazbeck Daveltov, University of Sheffield
Novel long-acting analgesic for chronic pain.
Chronic pain is a major health problem affecting one in five adults. It has a substantial impact on patients’ quality of life and presents a huge socio-economic burden. Despite increased understanding of the biological mechanisms underlying chronic pain, there is still no reliable treatment. Current methods used to treat pain cause a significant number of side effects and they rarely work long-term. It has been recently discovered that botulinum neurotoxins are able to reduce for months certain pain conditions, alongside their paralytic effects on muscles. Our research demonstrated that we can remove the paralytic effects and also enhance the long-lasting analgesia. This provides a new and exciting therapeutic strategy for the treatment of chronic pain, especially neuropathic pain conditions unresponsive to standard treatments.
We have developed a process that is able to re-engineer the native botulinum molecule to target specifically neurons associated with pain signaling. By eliminating the effects at the neuromuscular junction, this results in a safer, non-paralytic molecule that can still silence pain neurons for months after a single application. Using this novel molecule we have shown that it is possible to reverse some aspects of the pain pathway in an animal model of cancer-drug induced neuropathy. Chemotherapy-induced peripheral neuropathy is a severe side effect often associated with several chemotherapeutic agents. Studies on cancer survivors have revealed significant difficulties with activities of daily living and impaired physical and psychological health due to chronic pain.
Our aim now is to elucidate biological mechanisms of long-lasting analgesia and test our novel molecule in additional models of neuropathic pain to determine its suitability as an alternative treatment for prevalent chronic painful conditions. The funding will allow us to complete characterization of the unique long-acting analgesic and prepare a high-quality publication in a peer-reviewed journal facilitating translation towards novel long-lasting pain relief.
Novel long-acting analgesic for chronic pain
Grant to Dr Bernhard Frank, Walton Centre NHS Foundation Trust
Additional funding for TMS operator.
Grant to Dr Andreas Goebel, University Liverpool
Additional Funding for Lab Technician.
A Research Grant to Emma Begley, Liverpool John Moores University
A qualitative study on opioids in the management of chronic pain
A PhD Studentship to Dr U Alam, University of Liverpool
Defining small fibre neuropathy & neuropathic pain in idiopathic fibre neuropathy& chemotherapy.’ induced peripheral neuropathy.
The aim of this PhD studentship is to develop a highly skilled future pain researcher, through novel research and training embedded within a multi-disciplinary team of experts in peripheral neuropathy, pain medicine, neurophysiology and corneal ophthalmology. Moving forward, this PhD studentship will equip the candidate with transferable skills of image analyses, laboratory analyses and clinical techniques in pain assessment.
We hypothesise that the non-invasive real-time ocular imaging technique of corneal confocal microscopy can detect damage to the small nerve fibres (which are the same type of nerve fibres that conduct pain) as accurately as skin biopsy. We also hypothesise that damage detected in small nerve fibres by corneal confocal microscopy and skin biopsy are related to the types of pain felt. This PhD studentship will assess people with the painful conditions of idiopathic small fibre neuropathy (ISFN) and chemotherapy-induced neuropathy (CIPN).
A PhD Studentship to Dr Abbie Jordan, University of Bath
A double burden? A multi method investigation into the experience of paediatric chronic pain and mental health symptoms.
Through a series of novel yet related studies, this studentship will provide a detailed account of the challenges that youth who experience chronic pain and mental health symptoms face and how these challenges form barriers to their treatment. The first study will include a review of the current literature to better understand the evidence concerning the relationship between chronic pain in youth and mental health symptoms. The second study will involve collecting questionnaire and interview data over two-time points from 100 youth aged 11-19 years and their parents/caregivers regarding their pain-related disability, mental health symptoms and social relationships. The final study will use interviews and an online survey to explore how 50 clinicians think about treating youth with chronic pain and mental health symptoms and associated challenges faced in this treatment process.
Study findings from this series of PhD studies will be used to provide important insights into the challenges and impact of living with chronic pain and mental health symptoms in youth. This new knowledge will inform the existing treatment of chronic pain and mental health in youth, enabling healthcare professionals to better support youth and their families
(2018 – 2021)
A research grant to Dr David Andersson, Kings College, London
Neuronal basis of pain produced by passive transfer of Fibromyalgia from patient to model.
Fibromyalgia is one of the most common causes of chronic pain worldwide. There is no diagnostic test available and patients are diagnosed on how severe and widespread their pain is and whether they have other symptoms, e.g. fatigue, sleep problems and depression. Treatment of fibromyalgia is focused on exercise and education, which help patients become more active and cope better with pain. Drugs that are used to treat pain in fibromyalgia are effective in some patients, but often cause problematic side effects and regularly become less effective with time. Fibromyalgia has a serious impact on quality of life, and the fact that patients look healthy, can make it difficult for them to convince their environment about how they feel and to qualify for benefits. The cause of fibromyalgia remains unknown, but an improved understanding of the condition will accelerate development of treatments and diagnostic tests.
Neuronal basis of pain produced by passive transfer of Fibromyalgia from patient to model During this project, we will identify how fibromyalgia antibodies cause pain and sensitivity by acting at pain-sensing nerves, and whether a subgroup or all patients have these antibodies. It is likely that our work will lead to improved treatment of fibromyalgia in the future.
A research grant to Dr Paul Strutton,Imperial College London
The effects of non-invasive brain stimulation on chronic pain & central sensitisation in patients with radicular low back pain(sciatica) randomised sham-controlled proof of principle.
The body has pain control systems in the brain which can alter the changes in the spine and many drugs used to treat chronic pain work in this way. However, they are associated with side effects and often do not work. There are now new, drug-free ways to treat chronic pain which involve activating the brain with a safe, easy to deliver electrical stimulus applied to the head. This approach has been used many times in patients with chronic pain, however we still do not know if the pain relief is due to changes in the spine.
In this study, we will investigate the effects of brain stimulation on the changes in the spine that lead to chronic pain in patients with sciatica. To do this, we will note patients’ chronic pain and will use a simple pain test on the leg. These assessments will be done before and after brain stimulation on 5 consecutive days. The patients will return 7 and 21 days later and will have the same assessments, this time without brain stimulation. This will be done to see if the daily treatment has any longer lasting effects on their chronic pain. A longer term follow-up at 2 months will also be carried out.The new knowledge that we will generate will help us understand how this new treatment works to reduce chronic pain.
A PhD Studentship to Dr Abbie Jordan, University of Bath
Keeping on track: Exploring socio-developmental challenges faced by young people with ongoing pain and their families
This PhD studentship will involve conducting a number of related studies to examine some of the particular difficulties that young people with ongoing pain report with engaging with everyday teenage activities. Such difficulties might include visiting friends or becoming more independent from parents. We will use a variety of different research methods to examine exactly what these challenges look like for young people and how these challenges affect the lives of young people who experience ongoing pain and families. Study findings will help healthcare professionals to work with young people and their families to identify ways of supporting young people to engage with age appropriate teenage activities despite experiencing pain
(2017 – 2020)
A PhD Studentship to Dr Sarah Flatters, Kings College, London
‘Causal mechanisms of chemotherapy- induced painful neuropathy’
Chemotherapy-induced painful neuropathy (CIPN) is the major dose-limiting side-effect of several widely-used, first-line chemotherapeutics impacting survival and quality of life in millions of patients worldwide, every year. There is no treatment to prevent or reverse CIPN. Thus, the emergence of neuropathy causes dose reduction or cessation of effective cancer treatment, limiting patient survival. This studentship aims to facilitate the development of adjunct therapies for CIPN by understanding how CIPN occurs.
(2017 – 2020)