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.
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)
A research grant to Prof Qasim Aziz, Queen Mary University of London
‘Partnered study: A prospective, randomized study of PARAsympathetic modulation with slow deep breathing for the management of oesophageal pan hypersensitivity in Non o Erosive Reflux Disease’
Slow deep breathing has long been recognised to be important for relaxation and has been used in yoga, and mindfulness strategies. There has been recent evidence that this technique can also be helpful in pain management. We have done a pilot study in health subjects and shown that it works in reducing oesophageal (gullet) pain to acid infusion.
We now want to do a study of slow deep breathing in patients who have increased oesophageal sensitivity due to recurrent acid reflux to see if we can improve their symptoms without the use of drugs that tend to cause side effects. Success in our studies will open the way for this method to be used in other painful conditions such as Irritable Bowel Syndrome and Fibromyalgia.
(2017 (6 months))
A research grant to Dr Andrew Marshall, Liverpool John Moores University
‘Investigating the second order spinal projection pathway of C- Tactile afferents and their contribution to pain processing’
(2017-2019) (15 months)
A research grant to Dr Michael Bonello, Walton Centre NHS, Foundation Trust, Liverpool
‘Open-label pilot study using repetitive transcranial magnetic stimulation as a treatment for pain in Parkinson’s disease’
Transcranial magnetic stimulation (TMS) is a procedure that has been shown to improve pain in chronic sufferers. It is a well-tolerated procedure that can be performed on an outpatient basis. It uses a plastic covered coil that sends a magnetic pulse through the skull into the brain and by targeting particular areas in the brain it can be used to help modulate the perception of pain.
We intend to study the use of this technique to treat such a disabling symptom in patients who suffer from Parkinson’s Disease (PD). Initially we want to study this technique in ten patients who are suffering from pain and have PD. These patients would initially require an MRI scan which allows us to map the brain and target the correct brain areas for the delivery of the stimulation. The stimulation would be performed over twelve sessions and the patients would be assessed by a clinician using well recognised clinical tools.
We anticipate a meaningful improvement in pain. We also anticipate it is a safe technique to use in patients with PD. We intend to use this study to help plan a future study that compares TMS with sham technique to prove whether TMS could be an option in the treatment of such a disabling condition.
A research grant to Jilly Horner , Liverpool John Moores University
‘Living with Fibromyalgia- the patient perspective’
A Grant to Prof Nurmikko and Dr Bernhard Frank
‘Transcranial magnetic stimulation (TMS) for clinical use’
A research grant to Dr Fionnuala Lundy, Queens University Belfast
Epithelia Exosomes: Key Modulators of neural function in human trigeminal nerve
A research grant to Professor John Quinn, University of Liverpool
The potential for retrotransposon mobilisation to modulate sensory loss in ageing
A research grant to Dr Sandrine Geranton, University College London
Treating chronic pain by inhibiting SKBP51:An investigation in clinically relevant models
A research grant to Dr Andrew Marshall, Dr Francis O’Neill and Professor Francis McGlone, Salford Royal NHS Foundation Trust and Liverpool John Moores University
Developing a model to evaluate C-tactile fibre contribution to allodynia and for testing new topical medications
A research grant to Dr Andreas Goebel, Department of Translational Medicine, Liverpool University
Development of the Complex Regional Pain Syndrome (CRPS), Passive-Transfer-Trauma Model for Drug Research
A research grant to Dr David Anderson, King’s College London
The effects of Complex Regional Pain Syndrome (CRPS) Patient Serum-igG on Rodent Sensory Nerves