PhD Studentships in Arthritis Pain Research

Current Studentships

Personalised approaches to the management of chronic musculoskeletal pain in people with Rheumatoid Arthritis - Aya Ahmed Abd Elkhabir
Prevalence and risk factors of foot OA between ex-professional footballers and the general population - Ahmed Thanoon
Knee pain and multimorbidity in retired male professional football players and general population control men - Monirah Shuaib
Investigating opioid tolerance at the cellular level and its relationship with its behavioural manifestations - Lauren Brown
Epidemiology of Chronic shoulder pain and associated risk factors in the United Kingdom: a population-based study of UK primary care data using clinical practice research datalink (CPRD) - Nouf Al-Otaibi
Role of the gut microbiome and serum metabolome in knee pain in patients with Osteoarthritis - Ojasvi Mehta
Onosi Ifesemen
Postoperative pain assessment and opioid utilisation following colectomy - Reham Baamer
Arthritis damage and pain: VEGF involvement - Roheena Sohail
Understanding pain mechanisms in knee osteoarthritis - Yasmine Zedan
Virtual Reality for Chronic Low Back Pain: A Mixed Methods Feasibility Study in the Kingdom of Saudi Arabia - Fahad Alotibi
Co-Design of Assistive Robotic Systems for Monitoring and Management of Chronic Pain - Angela Higgins
Arabic translation, cultural adaptation, and psychometric validation of a measure of patient’s outcome expectations in the musculoskeletal population - Walid Mohamed
Arabic translation, cultural adaptation, and psychometric validation of ameasure of patient’s outcome expectations in the musculoskeletal population - Maria Alshammari
Investigating the ability of medulloblastoma derived extracellular vesicles to modify the development of mouse primary cortical neurones - Sophie McCann
The effect of inflammatory signalling on DRG sensory neuronal excitability - Rebecca Pope
Age related changes in serotonergic pathways and pain processing - Prajakta Bhoir
Early life exposure to opioids and pain in later life - Neave Smith
Alternative splicing targets in arthritis - Charles Besidonne

Current studentships

Ahmed Thanoon

Commenced: October 2019; Supervisors: Weiya Zhang and Michael Doherty

Prevalence and associated risk factors of foot/ankle OA in male ex-professional footballers compared to men in the general population in the UK

Introduction

Foot and ankle OA (FAO) can significantly impact an individual's quality of life, causing pain, disability, and decreased mobility. However, it is still unclear whether the prevalence of FAO is higher in professional footballers compared to the general population. It is important l to identify the prevalence and risk factors of FAO in footballers to understand the long-term consequences of the sport and to inform the development of potential preventative and treatment strategies. Such information is relevant to football associations, unions, and stakeholders interested in the health of retired and current professional football players. The current study examines whether male retired professional footballers have a higher risk of FAO than control men in the general population.

Objectives

1. To compare the prevalence of self-reported FAO, defined by foot and ankle pain, self-reported FAO, and ankle/toe surgery, between male retired professional footballers in the UK and general population control men in the East Midlands using a postal questionnaire.

2. To determine the prevalence of symptomatic and asymptomatic radiographic FAO in a sample of retired professional footballers and general population control men who returned the questionnaire, irrespective of FAO status.

3. To determine football-related risk factors for radiographic FAO in male retired professional footballers.

4. To compare the differences in self-reported quality of life and performance-related functional outcomes (using four square step test and the 10-metre walk test, undertaken in the same participants that underwent radiographic assessment) between male retired professional footballers and the general population control men.

Walid Mohamed

Commenced: April 2022; Supervisors: Paul Hendrick

Arabic translation, cultural adaptation, and psychometric validation of a measure of patient’s outcome expectations in the musculoskeletal population

BSc, MSc in physiotherapy PhD student at the School of Health Sciences, University of Nottingham, Nottingham.

Mohamed is a senior lecturer at the Faculty of Medical Technology at Bani Waleed University, Bani Waleed, Libya, in the Department of Physiotherapy. He is a senior physiotherapist working either independently or with a variety of clinics in Libya.

He is currently doing a PhD on patient outcome expectations. His research is about translating, cross-culturally adapting, and psychometrically validating a measure of outcome expectations.

He is a researcher who is interested in musculoskeletal disorders, rehabilitation, physiotherapy, self-reported measures, psychometric properties, and patient expectations, with experience in systematic reviews.

Angela Higgins

Commenced: 1st October 2022; Supervisors: Praminda Caleb-Solly, Steve Benford, Holly Blake and Michelle Hall

Co-Design of Assistive Robotic Systems for Monitoring and Management of Chronic Pain

Chronic pain can be difficult to detect and diagnose, as pain levels fluctuate for an individual daily. Therefore, sensors in the home may be suitable for monitoring the effects of pain over a period much longer than a clinical consultation. However, if we are to place sensors within the home, we need to understand how they can collect data which is sufficient to inform the user and clinician about health status, whilst still being acceptable to that end user.

If pain can be sensed and understood, there may be the opportunity to develop assistive technology that can then respond appropriately and be integrated with pain management plans. Robotic pain management interventions using distraction or relaxation techniques have shown promise, but little research has been conducted to understand the desires of older adults experiencing pain, despite this being the largest pain demographic.

Alongside the PhD industry partner, ExtraCare Charitable Trust, this project will include a series of co-design activities alongside older adults living with pain within retirement villages. Using surveys, interviews, focus groups, and other design workshops, we hope to understand the needs of this demographic to develop assistive robotic technologies for pain management, with a particular focus on acceptability, usability, and accessibility.

Fahad Alotibi

Commenced: 01/10/2021 Supervisors: Paul Hendrick and Fiona Moffatt

Virtual Reality for Chronic Low Back Pain: A Mixed Methods Feasibility Study in the Kingdom of Saudi Arabia

Immersive virtual reality (VR) is a computer-generated device that covers all the user’s points of view. Immersive VR is utilised to rehabilitate patients with various conditions associated with pain. However, there is growing interest in utilising immersive VR for musculoskeletal pain. This is important as chronic low back pain (CLBP) has been considered a leading cause of disability among adults for three decades, with limited treatment options approved by international guidelines. In addition, the feasibility of new technology is influenced by contextual and sociocultural factors. Moreover, few studies investigated immersive VR's feasibility, acceptability, and tolerability among patients with CLBP and in the Kingdom of Saudi Arabia (KSA).

Therefore, this study follows the Medical Research Council’s framework for complex interventions. Initially, an overview of systematic reviews was conducted to investigate the effectiveness of VR in patients with musculoskeletal pain and disability. In addition, patients and public involvement groups played an active role in informing the development of the immersive VR protocol designed to test the feasibility of administering the immersive VR intervention for patients with CLBP in the KSA. Therefore, a mixed-methods, explanatory sequential study design is conducted in a single-centre setting, comprising a one-group pre-intervention and post-intervention feasibility trial. Qualitative semi-structured one-on-one interviews with patients and HCPs follow the quantitative phase. The study is expected to lead future research in the field.

Nouf Al-Otaibi

Commensted: 1st April 2021; Supervisors: Michelle Hall, Weiya Zhang, Subhashisa Swain, Michael Doherty

Epidemiology of Chronic shoulder pain and associated risk factors in the United Kingdom: a population-based study of UK primary care data using clinical practice research datalink (CPRD)

Chronic shoulder pain is a common complaint that annually affects between 5% and 47% of the adult population worldwide. In the United Kingdom (UK), it was estimated that 2.4% of people aged between 18 and 60 years consulted their general practitioners (GPs) for shoulder pain in 2005, and the number of consultations in primary care for shoulder pain appears to be increasing. Prevalence of shoulder pain increases with age and is higher in women than in men. However, whether the occurrence of shoulder pain has changed in the past 20 years in the UK, its variations between regions and its major consequences remain largely unknown. This PhD project aims to to investigate the current prevalence and incidence of chronic shoulder pain, the trend in the past 20 years, variation between different areas, and related risk factors in the UK population aged 40 years and over using electronic health record.The project will also include a systematic review to summarise the evidence around the prevalence and incidence of chronic shoulder pain and its related risk factors

Monirah Ali Shuaib

Commenced: 1st February 2021; Supervisors: Prof. Weiya Zhang, Prof. Michael Doherty, Dr Michelle Hall and Dr Subhashisa Swain

Knee pain and multimorbidity in retired male professional football players and general population control men

Retired professional footballers have a higher injury rate of lower limbs joints. These injuries might results to short and long-term effects such as chronic pain and osteoarthritis (OA). However, they may be less likely to have other long-term conditions such as diabetes, cardiovascular disease and cancer due to their levels of physical fitness but a higher prevalence of mental health problems. The presence of multimorbidity (≥2 long-term conditions) is increasing within the general population but whether footballers are more or less likely to have multimorbidity remains unknown. The association between professional footballers and risk of long-term health consequences, including OA and multimorbidity after retirement, is an important concern due to its impact on their health, wellbeing and quality of life. The aim of this PhD is to examine the incidence of knee pain (KP) and multimorbidity in male retired professional footballers compared to men in the general population.

Objectives

To systematically review published observational studies of long-term conditions in professional footballers compared to the general population.
To examine the incidence of KP and multimorbidity in retired professional footballers and general population male controls who undertook postal surveys between 2014 and 2021.
To examine the temporal association between KP and multimorbidity (and specific comorbidity), and to examine the proportional risk contribution of the collected risk factors to multimorbidity.
To examine the association between knee OA and ankle/foot OA within footballers and general population controls using radiographic assessment.

Reham Baamer

Commenced: 1 October 2019 Supervisors: Roger Knaggs, Li Shean Toh, Dileep Lobo

Postoperative pain assessment and opioid utilisation following colectomy

Opioid analgesics have an established role in managing acute pain following surgery and may facilitate recovery. However, several factors have recently contributed to an increase in persistent postoperative opioid use in some countries. These factors include the reliance on unidimensional pain assessment tools, use of different types and formulations of opioids along with varying patterns of opioid prescribing. Persistent opioid use is now widely acknowledged as a surgical complication which can be associated with a range of harms, including physical dependence, tolerance, and opioid diversion. Despite the risk of persistent opioid use after colectomy being assessed in the US and Canada, the extent to which this complication exists within the UK remains unexplored. This PhD project aims to identify trends of opioid prescribing, and the prevalence and predictors of persistent post-discharge opioid use following colectomy using linked electronic healthcare data from England. The project will also include a systematic review to summarise the evidence around pain assessment tools used following surgery and identify novel tools that assess how pain interferes with functional recovery

Ojasvi Mehta

Start date: October 2019. Supervisor: Prof. Ana Valdes

Role of the gut microbiome and serum metabolome in knee pain in patients with Osteoarthritis

Knee osteoarthritis (OA) is a multifactorial disease initiated with inflammation and pain which later progress to joint deformation and disability. There has been an increase in the global burden of knee pain and OA reducing the quality of life over the past few years. The available treatments of pain-analgesics, however, have been reported to be having certain side effects. With the growing evidence of gut microbiome associated with many other inflammatory diseases, the gut microbiota has been regarded as a crucial contributing factor in the development of OA. It's already established that gut microbes are responsible for degrading the dietary compounds or the host-produced compounds and converting them to a diverse range of metabolites. This project aims to investigate the association of gut microbiome and serum metabolome with knee pain in OA patients. This is further explored by looking into the metabolic pathways that are relevantly involved in knee pain and OA that could be targeted for potential metabolites-based therapeutics.

Aya Abd Elkhabir

Start date: October 2021. Supervisors: Prof. David Walsh and Dr Daniel McWilliams

Personalised approaches to the management of chronic musculoskeletal pain in people with Rheumatoid Arthritis

Chronic pain is a major cause of disability worldwide. There is discrepancy between the pain level and the actual tissue damage. Central sensitisation, defined by IASP as increased responsiveness of nociceptive neurons in CNS to their normal or subthreshold stimuli, has been implicated in this discrepancy. Various rheumatological conditions showed features of central sensitisation (CS) such as fibromyalgia, rheumatoid arthritis, and osteoarthritis. Central sensitisation is usually associated with poor treatment outcomes, so it is important to reduce it. Exercise has the potential to decrease CS. This effect is robust in pain-free population, however in people with chronic pain it might be more dependent on exercise dosage. Although the mechanisms underlying exercise-induced hypoalgesia are not completely understood, it was found by many researchers that it has a robust effect on the descending inhibitory pathways. Other studies showed that exercise inhibits the facilitatory pathway by investigating the effect of exercise on temporal summation. Additionally, it was observed by neuroimaging that exercise might have effects on brain neurobiology in a chronic musculoskeletal pain population. My hypothesis is that Exercise reduces central nervous system mechanisms that increase pain in people with rheumatoid arthritis. My aim is to design the optimal exercise program to reduce central sensitisation.I will start my research project by doing a systematic review to underpin the exercise intervention/s types and dosage/s associated with the greatest reductions in indices of CS. After that, an RCT in people with rheumatoid arthritis will be designed comparing exercise with control to explore the effect of the exercise therapy on central sensitisation mechanisms of pain in RA population.

Previous studentship

Portrait picture of Dimitris Amantis

Dimitros Amantis

Commenced: October 2017

Supervisors: Lucy Donaldson

Peripheral contributions to the developing and maintenance of chronic pain in osteoarthritis in the knee joints

Practically I will aim to understand how pain progresses during the disease specifically in the peripheral nervous system in conjunction with the signalling to the CNS.

Moreover, given the inconsistency of the drugs that currently exist against OA, I will focus my research on understanding the basic mechanisms of VEGFA isoforms when used against OA, since there are evidence that targeting VEFGA can reduce pain. However the question of what happens to the inflammation still stands. Moving forward in the next steps of the PhD I will try to tackle the question of how inflammation progresses and alters in conjuction to pain.

Wendy Chaplin

Commenced: October 2019

Supervisors: David Walsh, John Gladman and Dan McWilliams

Investigating musculoskeletal pain and frailty

As the average lifespan increases, the number of years in good health struggles to keep pace. Accumulation of currently incurable conditions with increasing age leads to increasing health impairment and reduced quality of life. Musculoskeletal pain, for example, due to osteoarthritis, is increasingly prevalent, and, as well as directly causing distress, contributes to reduced independence and increases health care and societal costs. Knee osteoarthritis causes severe pain and reduced mobility, and reduced activity and increasing sedentary behaviour contribute to increased morbidity and mortality. Frailty is a vulnerability state seen in older people due to multi-organ age-associated decline and is characterised by homeostatic failure in response to challenge. Understanding the link between musculoskeletal pain and frailty may help develop and target treatments that facilitate healthy ageing.

This project takes advantage of the multidisciplinary research environment and patient cohorts developed in Nottingham within the NIHR Nottingham Biomedical Research Centre and Pain Centre Versus Arthritis. The Investigating Musculoskeletal Health and Wellbeing survey is a questionnaire-based research study which collects annual information from people with different degrees of pain and frailty.

Ayah Ismail

Commented: October 2018

Supervisors: Weiya Zhang, Michael Doherty, Michelle Hall

Optimising Contextual Factors in the Practitioner-Patient Encounter inthe Management of Osteoarthritis

Contextual effect is integral in the overall treatment effect of any given intervention. In osteoarthritis, 75% of the treatment effect is attributable to the contextual effect. In my PhD project I investigated the effect of contextual factors and placebo effect in patients osteoarthritis. The research aim is to develop a contextual enhancement package to enhance the overall treatment effect. The UK Medical Research Council framework for complex intervention development was followed to develop the CEP. Five sub-studies have been conducted in the development phase: a Delphi consensus among international experts in placebo research; a systematic review (SR) of randomised control trials (RCTs); a SR of qualitative studies; a survey of stakeholders; and public and patient involvement (PPI) throughout the development.

Adrian Haywood

Contributions of spinal and supraspinal sites to the pain assocated with osteoarthritis

Adele Edwards

Developmental changes in neural stem cell responses in the spinal cord and the influence of painful stimulation

Amanda Lillywhite

Investigation of the influence of innate anxiety on functional connectivity in animal models of osteoarthritis pain

Junting Huang

Investigation of inflammatory mechanisms in models of osteoarthritic pain

Luting Xu (Tracey)

The role of TRPV1 signalling in osteoclastogenesis and pain in osteoarthritis

Kun Zuo

The contextual effect of treatment in osteoarthritis

Hamza Alshuft

Structural brain changes in chronic pain of knee osteoarthritis

Louis Brailsford

The role of lipid signalling in osteoclasts: contributions to osteoarthritic pain

Xi Chen

The placebo effect and its determinants in fibromyalgia

Charles Greenspon

Postnatal neurophysiological development of nociception: integration and representation into supraspinal networks

Fatimah Almahasneh

Role of prostaglandins in the periaqueductal gray in the central modulation of osteoarthritis pain

Meesawatsom Pongsatorn (Den)

Targeting the resolution of inflammation to reduce spinal excitability and pain

Lilian Nwosu

Structural pain modification in models of osteoarthritis

Monica Persson

Relative efficacy of topical NSAIDs and topical capsaicin in osteoarthritis and neuropathic pain

Laura Stoppiello

Structural associations of pain in human knee osteoarthritis

Subhashisa Swain

Subhashisa Swain

Commenced: February 2018

Supervisors: Weiya Zhang, Carol Coupland and Mike Doherty

Epidemiology of Osteoarthritis and it’s comorbidities

Epidemiology of Osteoarthritis and it’s comorbidities

Osteoarthritis (OA) is one of the common chronic conditions in older people and often causes chronic joint pain and disability. Despite the rise in multimorbidity there is little information available on the proportion of people with OA have multiple chronic conditions and how it changes with time. According to a recent research, three out of ten people in the UK have more than at least one long term condition. However, the pattern and association of these conditions with OA is not well understood.

This research aims to use advanced statistical techniques to understand the epidemiology of OA in the UK and multiple chronic conditions associated with. Furthermore, the risk, burden and impact of multiple chronic conditions in OA will be studied in detail.

Emma Battell

Emma Battell

Commenced: October 2017

Supervisors: Gareth Hathway and Lucy Donaldson

Investigation postnatal changes in the connectivity and physiological role of the periaqueductal grey and how this affects descending pain pathways

Supraspinal centres serve critical roles in producing behavioral responses to pain and modulating the excitability of spinal pain networks. This descending pain modulation system (DPMS) comprises several centres in the brain with the periaqueductal grey (PAG) serving as an integrative centre. The PAG has
significant afferent input from the forebrain and limbic system and an efferent projection to the brainstem.

Significant postnatal changes occur in the PAG and brainstem that profoundly effect sensory processing. This project aims to detail changes in the function and connectivity of the PAG across postnatal development.

Afroditi Kouraki

Commenced: May 2019

Supervisors: Professor Ana M. Valdes, Dr Tobias Bast, Professor Eamonn Ferguson

A biopsychosocial approach to understanding the contributors to chronic pain

This project utilised both advanced statistical analysis and clinical-based research to identify how psychological (anxiety and cognitive ability), social (social deprivation/isolation, education) and biological (genetics and the gut microbiome) factors interact in their contribution to chronic pain.

We identified common threads that link cognitive ability and anxiety with social and biological factors regardless of whether we looked at a clinical sample, a longitudinal panel, or genetic and gut microbiome data. These multilevel findings link together the pathways through which psychological, social and biological factors contribute to pain mechanisms and pain-related outcomes and suggest that chronic pain is a complex phenomenon that we have to approach from a holistic point of view.

Khalid Yaseen

Khalid Yaseen

Commenced: October 2017

Supervisors: Abhishek Abhishek, Michelle Hall, Mike Doherty and Weiya Zhang

Individualised exercise intervention for hip and knee osteoarthritis

Khalid was doing a systematic review, Delphi study and feasibility study to develop optimal individualisation methods for exercise to treat osteoarthritis.

Polykarpos Angelos Nomikos

Commenced: December 2017

Supervisors: Abhishek Abhishek, Michelle Hall, Roshan das Nair and Ana Waldes

Developing and evaluating the feasibility of a nurse-led complex package of care for knee pain.

Knee OA manifests clinically with pain, stiffness and disability. Knee pain is a common problem, with 25% of the population older than 55 years in age having persistent knee pain and knee pain present on most days of the previous month, is present in one in five adults over the age of 40 years.

National Institute for Health and Care Excellence (NICE) have recommended core, adjunctive non-pharmacological and pharmacological treatments for OA. However, core treatments suggested by NICE are under-utilised as both doctors and patients often focus predominantly on pharmacological systemic analgesics alone. Doctors do not appear to be best suited for managing knee pain due to OA. Even enhanced GP consultations based on an OA guidebook followed by referral to a practice nurse-led OA clinic and provision of a written information on OA did not improve several quality indicators for knee OA.

The overall purpose of the study is to test the feasibility of conducting a RCT of a nurse-led complex intervention comprising education, non-pharmacological and pharmacological principles of management of OA and knee pain.

Gabriela Sandoval-Plata

Gabriela Sandoval-Plata

Commenced: October 2018

Supervisors: Abhishek Abhishek and Kevin Morgan

Gene expression analysis and Risk of gout: a case-control study

Gout is one of the most common forms of inflammatory arthritis, with a prevalence of 2.49% in the UK. It is characterised by abrupt episodes of acute inflammation and severe pain in joints due to monosodium urate (MSU) crystals deposition as a consequence of hyperuricemia. Despite being crucial to gout, hyperuricemia does not necessarily cause the disease, but the reasons underlying the progress from asymptomatic crystal deposition in people with hyperuricemia to gout remains unclear. Moreover, clinical variation among patients with gout in terms of the age of onset, frequency of attacks and the development of tophi is still poorly understood.

Based on the fundamental role of the NLRP3 inflammasome and toll-like receptors (TLR) pathway in the immune response to MSU crystals, the aims of the present project is to analyse gene expression of inflammasome and TLR-related genes to: (1) evaluate if it is influenced by serum uric acid levels, (2) evaluate whether a differential expression is associated to the development of symptomatic gout, and (3) explore the expression profile during acute and intercritical gout. In addition, polygenic risk models will be developed to distinguish gout cases vs controls, and to determine risk for gout in people with hyperuricaemia who has not developed gout.

Asta Tranholm

Commenced: October 2017

Supervisor: Cornelia de Moor

Understanding the role of messenger RNA regulation in pain nerves during osteoathritis

Hyperalgesia is a recognised feature of osteoarthritis which is at least in part due to changes in nociceptor neurons that innervate the joint. Regulation of local protein synthesis by mRNA localisation and cytoplasmic polyadenylation have recently been implicated in nociceptor plasticity. It has been shown that the polyadenylation inhibitor cordycepin affects pain behaviour in rodent models of osteoarthritis (OA). This project will aim to increase our knowledge of which mRNAs are localised and polyadenylated in nociceptor neurons and their role in hyperalgesia. Advanced gene therapy techniques will be utilised to evaluate the role of polyadenylation in regulating protein synthesis of specific mRNAs in axons of pain nerves in cell culture systems as well as a mouse model of OA.

Sameer Gohir

Sameer Gohir

Commenced: January 2018

Supervisors: Paul Greenhaff, Ahbishek Abhishek and Ana Valdes

Digital Exercise Intervention for Knee OA – Link between sleep and pain relief

Practically I will aim to understand how pain progresses during the disease specifically in the peripheral nervous system in conjunction with the signalling to the CNS.

Burak Kundakci

Burak Kundakci

Commenced: April 2017

Supervisors: Abhishek Abhishek, Michelle Hall, Mike Doherty and Weiya Zhang

Identifying key elements of non-pharmacological treatment package for fibromyalgia: Evidence synthesis and Delphi exercise

Fibromyalgia (FM) is a common chronic condition that manifests with chronic widespread pain or multiple regional pain, and with other associated core symptoms of fatigue, non-restorative sleep and cognitive dysfunction. After osteoarthritis, FM is the second most common rheumatologic condition, and affects 2-8% of the whole population. Universally guidelines on the management of FM support a multi-faceted approach combining non-pharmacological interventions as first-line therapy and pharmacological interventions as adjunctive treatment, with an emphasis on an individualised patient-centred approach.

The overall purpose of the research project is the development of an optimal non-pharmacological treatment package for FM. It primarily aims to estimate the efficacy and relative efficacy of all non-pharmacological interventions, select the most efficacious, accessible and applicable interventions and bring them together as a package of care. Firstly, studies comparing a non-pharmacological intervention versus a non-intervention will be used to calculate overall effect sizes for each non-pharmacological treatment by conducting a conventional meta-analysis. Secondly, these treatments will be prioritised by Network Meta-Analysis using direct and indirect evidence. Finally, a Delphi exercise (consensus building) will be undertaken among patients and healthcare professionals to select the most effective and accessible interventions.

Arman Tadjibaev

Arman Tadjibaev

Commenced: October 2016

Supervisors: Dorothee Auer and Sarina Iwabuchi

A link between chronic pain and anxiety

A link between chronic pain and anxiety

Incidence of anxiety disorders among chronic pain patients is disproportionately higher than in general population. Anxious pain patients are characterized by decreased pain thresholds, increased pain levels, more daily complaints, poorer quality of life and worse outcome of treatment. Underlying mechanisms of negative influence of anxiety on pain are still poorly understood.

The main aim of my research is to understand neural mechanisms of coexistence of two disorders and to suggest new methods of treatment and management of chronic pain conditions with co-morbid anxiety.

Adele Edwards

Commenced: September 2015

Supervisor: Victoria Chapman

Developmental changes in neural stem cell responses in the spinal cord and the influence of painful stimulation

Neural stem cells (NSCs) are highly proliferative cells that play a fundamental role in the generation of glial cells and neurones in the developing CNS. There are high numbers of NSCs in the CNS throughout development, however in adulthood they become confined to specific regions including the central canal of the spinal cord. The role of NSCs has been explored following adult spinal cord injury but whether they play a role in the spinal processing of pain is yet to be investigated. This project aims to investigate NSC expression in the spinal cord throughout normal postnatal development and identify whether there are changes in NSC responses following painful stimulation both in early life and adulthood.

Matthew Swift

Matthew Swift

Commenced: September 2016

Supervisors: Lucy Donaldson and David Bates

The Differential Roles of Vascular Endothelial Growth Factor Isoforms in the Context of Chronic Pain and Peripheral Neuropathy

Chronic pain is a major worldwide health burden with an asymmetry between prevalence and effective treatments. Additionally, chemotherapy induced peripheral neuropathy (CIPN) is emerging as a major contributor to the aforementioned burden, and a limiting factor in the supply of chemotherapy regimens. Thus, there is a large demand for the rapid development of novel analgesic drugs with which to counter the growing requirement for efficacious therapeutics.

One such approach is modulation of Vascular Endothelial Growth Factor (VEGF) synthesis. Different
isoforms of VEGF have profound neuroprotective and anti-nociceptive functions. Therefore, my project is centred on developing a series of potential therapeutics that would initiate synthesis of these VEGF isoforms over those that normally predominate in pain states. This provides a new and innovative approach to pain management therapy.

Amer Imraish

Commenced: October 2014

Supervisor: Gareth Hathway

Age-related Changes in the Phenotype of Spinal Microglia

Microglia play a central role in immune surveillance and modulation of neuroinflammation as well as playing a role in neurodevelopment. Microglia play a crucial role in the development of pathological pain in adults but not early in life however little detail is known about the changing phenotype of spinal microglia during development. This project aims to understand the age-related changes in spinal microglia following activation with pathogen- and damage- associated molecular patterns. This will be done by preparing microglial cultures from neonatal postnatal day (P) 1 adult (P40) rat spinal cords. Furthermore, this project is particularly interested in investigating the role of nuclear receptor Nr4a2 in modulating the microglial cells in neuroinflammation. Techniques including phagocytosis and nitric oxide production assays, and immunocytochemistry will be employed. We will also perform quantitative assessment (qPCR) of expression levels of key inflammatory genes in isolated microglial cells.

Lydia Sinnett-Smith

Lydia Sinnett-Smith

Commenced: October 2016

Supervisor: Victoria Chapman

Mechanistic studies of the transition from acute to chronic pain in osteoarthritis models

This project will examine the central and peripheral mechanisms involved in mediating the transition from acute to chronic pain in clinically-relevant animal models of osteoarthritis. These mechanisms will be investigated using both in vivo and ex vivo techniques, including single-unit spinal electrophysiology. Currently, changes in GABAergic signalling in the MIA model of OA pain are being explored using both agonists and antagonists of the GABA_A receptor.

Sara Goncalves

Sara Gonçalves

Commenced: September 2016

Supervisors: Vicky Chapman, Gareth Hathway and Tobias Blast

Mechanistic studies of the impact of chronic pain on brain, behaviour and cognition in rat models of osteoarthritis

This project aims to determine how chronic osteoarthritis (OA) pain affects two important everyday cognitive functions, memory and attention, by combining methods from pain research and behavioural and integrative neuroscience. The monoiodoacetate (MIA) model of knee OA in rats will be used to examine the impact on hippocampus-dependent memory and prefrontal-dependent attention, using the watermaze DMP and the 5CSRT tests, respectively. Furthermore, we will characterise changes within these key brain regions.

Emma Dayman

Emma Dayman

Commenced: October 2016

Supervisor: Victoria Chapman

Immunological contributions to age-dependent variations in response to cutaneous inflammation and the programming of later life pain

Pain pathways mature over the first weeks and months of life in rodents, and years in humans. In early life, thresholds to painful stimuli are lowered and behavioural responses to noxious stimuli are altered. Previous work has demonstrated that inflammatory stimulus leads to different nociceptive responses in the early life, compared with adulthood.

My research aims to characterise the ability of various inflammatory stimuli to prime the nociceptive pathways in early life, and identify key differences in immunological and pain responses between neonates and adults. Furthermore, we will determine the impact this has on the response of the nociceptive system to re-exposure to inflammatory signals later in life. This project will use a range of in vivo and in vitro approaches to compare inflammatory processes in response to single and repeat inflammation in cutaneous tissue at different postnatal ages in rats. Techniques including FACS analysis, immunohistochemistry linked to fluorescence microscopy and pain behaviour assays will be utilised. We will also perform quantification of alterations in the expression of key genes involved in inflammatory processing in isolated inflammatory cells.

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Alexandra Durrant

Commenced: October 2016

Supervisors: Lucy Donaldson and Nick Beazley-Long

Alterations in the central gliovascular barrier in response to inflammatory pain

Multiple pain states are known to have an impact on the functioning of gliovascular barriers such as the blood brain barrier (BBB) and blood spinal cord barrier (BSCB). These barriers are pivotal in controlling entry of potentially neurotoxic molecules and cells into the CNS and neural parenchyma, but under inflammatory conditions, barrier integrity can become compromised to allow infiltration of non-neuronal cells and can lead to glial cell alterations. This project aims to monitor the gliovascular alterations in response to peripheral inflammation, and to investigate the role of VEGFR2 in these changes.

Vasileios Georgopoulos

Vasileios Georgopoulos

Commenced: October 2016

Supervisor: David Walsh

Do pain mechanisms and levels of central sensitisation predict effective self-management in patients with Chronic Low Back Pain?

Pain mechanisms and levels of central sensitisation reflect changes in the central nervous system and pain processing which may impact on the ability of patients to effectively cope and manage their pain effectively. Identification of these factors may allow early targeted management for these patients. As central sensitisation is not present on all patients suffering from a chronic musculoskeletal condition, efficient stratification must be followed to examine in detail the effectiveness of self-management. From an extended scope, the findings of the project might influence self-management procedures in other chronic pain states such as fibromyalgia, whiplash, chronic neck pain etc. as pain mechanisms function in the same way and central sensitisation follows similar patterns regardless of the condition.

V-Simmonds-photo-rejig

Vicki Simmonds

Commenced: October 2013

Supervisors: John Harris and Carl Stevenson

Translational studies of central sensitization in the rat monosodium iodoacetate model of osteoarthritis pain

This project will use pre-clinical animal models of knee osteoarthritis (OA) to investigate the effects of chronic pain on descending inhibitory controls by looking at how diffuse noxious inhibitory controls (DNIC) modulate spinal nociceptive reflexes. DNIC can be evoked by applying a noxious stimulus to widespread areas of the body outside the peripheral excitatory receptive field of the reflex and previous studies have shown that dysfunction in these inhibitory pain pathways may be a key contributor to chronic pain. By investigating whether DNIC is altered in OA and the mechanisms underlying these alterations, we hope to increase our understanding of pain mechanisms during OA.

Siew Li Goh

Siew Li Goh

Commenced: October 2015

Supervisors: Weiya Zhang, Mike Doherty and Michelle Hall

Relative efficacy of different types of exercises in the treatment of knee osteoarthritis – a network meta-analysis of randomised controlled trials

Knee osteoarthritis (OA) is a common debilitating condition, especially amongst older people. The main treatment aims are to reduce pain and improve function. Various types of exercises, be it aerobic fitness or strengthening, land or aquatic - have generally been found to be beneficial in achieving these treatment goals. However it is unclear which of these exercises is more efficacious and whether there are an patient characteristics that predict treatment response. A network meta-analysis of randomised controlled trials will be used to establish the efficacies of these exercises in relation to a common comparator. Finally, in order to predict treatment response, an individual patient data (IPD) meta-analysis will be conducted.

Kehinde Akin-Akinyosoye

Kehinde Akin-Akinyosoye

Commenced: October 2015.

Supervisor: David Walsh

A clinical assessment tool to improve the use of pain relieving treatments in knee osteoarthritis

Phenotypes found to contribute to knee osteoarthritis (OA) pain via peripheral mechanisms and central mechanisms were used in the development of the questionnaire items. Items which discriminate between peripheral and central mechanisms of knee OA pain will be explored in order to develop a validated and reliable short clinical tool (which will include questions and, possibly, additional simple aspects of clinical assessment). Patient completed questionnaires will be considered for factor analysis to determine effective mechanism based stratification in patients.

Hamza Alshuft

Hamza Alshuft

Commencted: April 2010

Supervisor: R Dineen

Structural brain changes in chronic pain of knee osteoarthritis

Hamza was appointed to investigate the structural brain changes associated with chronic pain of knee osteoarthritis. Up-to-date structural image analysis tools were used to quantitatively analyse high-resolution brain images obtained using advanced MRI scanning techniques.

Louis Brailsford

Louis Brailsford

Commencted: January 2011

Supervisor: A Bennett

The role of lipid signalling in osteoclasts: contributions to osteoarthritic pain

Osteoclasts have an important role in bone remodelling and have been shown to contribute to bone cancer induced pain. Both clinical and preclinical evidence supports a role of osteoclasts in osteoarthritis, which is associated with bone remodelling and chronic pain. This project investigated the signalling pathways which mediate osteoclastogenesis using a combination of molecular biology, primary cell culture, mass spectrometry and fluorescence imaging techniques. The potential interactions of these signalling pathways with peripheral pain mechanisms were assessed in models of osteoarthritic pain.

Xi Chen

Xi Chen

Commencted: November 2011

Supervisor: W Zhang

The placebo effect and its determinants in fibromyalgia

The project investigated the placebo effect in fibromyalgia and its potential determinants in randomized controlled trials. Meta-analysis was used to summarise the placebo and nocebo effects for different types of placebos. The effect sizes were compared between fibromyalgia and osteoarthritis. The duration of the placebo effect and associated factors were examined.

Junting Huang

Junting Huang

Dates: September 2011 - July 2014

Supervisor: V Chapman

Investigation of inflammatory mechanisms in models of osteoarthritic pain

The contribution of peripheral and central inflammatory responses to pain responses associated with osteoarthritis (OA) will be studied in models of OA pain. Techniques will include behavioural studies of pain responses and ex vivo analysis of tissues from these models. Immunohistochemistry, western blotting and RT-PCR will be used to investigate expression levels of receptors, cytokines and other pro- and anti-inflammatory mediators in these models of OA pain.

Xu Luting photo

Luting Xu (Tracey)

Dates: October 2010 - Sept 2014

Supervisor: A Bennett

The role of TRPV1 signalling in osteoclastogenesis and pain in osteoarthritis

Luting (Tracey) focused on elucidating the mechanism underlying the formation of osteoclast in OA and how it was associated with OA pain. Molecular biology, gene expression analysis and cytohisochemistry techniques were employed. The PhD programme focusses on the TRPV1 signaling pathway, modulation by lipid metabolism and its relationship with pathological bone remodeling in osteoarthritic joints.

Kun Zuo

Kun Zuo

Dates: October 2011 - July 2014

Supervisor: W Zhang

The contextual effect of treatments in osteoarthritis

Kun undertook a project to examine the relative effect of placebo (contextual effect) in complementary therapy in osteoarthritis (OA). The PhD project investigated the effect size of the contextual effect for each complimentary treatment modality. Comparisons were made between treatments, as well as between OA and other chronic painful conditions (fibromyalgia and rheumatoid arthritis). Meta-analysis was used to combine results and different treatment categories and determinants of the contextual effect and related adverse events (nocebo effects) were also examined.

Adrian Haywood

Adrian Haywood

Dates: October 2011 - October 2015

Supervisor: V Chapman

Contributions of spinal and supraspinal sites to the pain associated with osteoarthritis

The objective of my studentship is to investigate the relative contributions of: sensory neurones that innervate osteoarthritic (OA) joints, and neurones in supraspinal centres that control pain responses; to the induction and maintenance of the chronic pain associated with OA. These studies will use models of OA pain to investigate changes in the expression of key neurotransmitters, receptors and non-neuronal cells at various time-points through the establishment of OA pain within the central nervous system. Electromyographic (EMG) and electrophysiological single-unit recordings will provide quantified data regarding the establishment of central sensitisation in the spinal cord.

Lilian Nwosu

Lilian Nwosu

Dates: October 2011 - October 2015

Supervisor: D Walsh

Structural pain modification in models of osteoarthritis

This project will use interventions in models of knee OA, with clinical validation where feasible, to explore the potential of modifying nerve growth and osteochondral permeabilisation as a sustained analgesic approach in OA. Effects on pain behaviour will be distinguished between those due to structural modification and short term analgesic effects according to their associations with structural change and persistence after treatment withdrawal, and by comparison with centrally acting analgesic agents. Possible confounding by inflammation will be addressed.

Laura Wyatt

Laura Wyatt (nee Stoppiello)

Dates: October 2011 - October 2015

Supervisor: D Walsh

Structual associations of pain in human knee osteoarthritis

A comparison of structural and biochemical factors in joint tissues from knees of patients undergoing joint replacement surgery for OA pain with those with similar degrees of chondropathy that have been obtained post mortem from people who have not sought help for knee pain. The development of key structural and biochemical changes with OA disease progression will be determined by comparing human tissues to OA models. Knee joint structural and biochemical changes predicting pain phenotype will be explored. Finally, one key molecular or structural target emerging from these studies will be tested in interventional studies in an appropriately validated model.

Charles Greenspon

Charles Greenspon

Dates: January 2015 - May 2018

Supervisor: G Hathway

Postnatal neurophysiological development of nociception: integration and representation into supraspinal networks

My project aimed to understand fundamental physiological aspects of chronic pain by understanding how both the spinal cord and brain respond and adapt to it. This was done using a model of arthritis so that any discoveries made are relevant to many people who are in pain. The techniques that this project developed should provide a framework for further comprehensive work to be done that may be more relevant in a clinical setting. Furthermore, this project was particularly interested in how the pathways and networks that are relevant to chronic pain develop in adolescence. Significant work was done to measure and understand how neural nociceptive-evoked activity changes over development.

Fatimah Almahasneh

Fatimah Almahasneh

Dates: April 2014 - March 2018

Supervisor: L Donaldson

Role of prostaglandins in the periaqueductal gray in the central modulation of osteoarthritis pain

The experience of pain in osteoarthritis (OA) is significantly affected by central pathways of pain modulation, where the midbrain periaqueductal gray (PAG) is known to play a crucial role through central sensitization and hyperalgesia. Prostaglandins (PGs) enhance nociceptive transmission both peripherally and centrally, and have been recognized as mediators of PAG-facilitated modulation of pain.

This study aims to look into the role of PGs in the PAG in the descending facilitation of nociception in OA using the monoiodoacetate (MIA) model, as well as the complete Freud's adjuvant (CFA) model of inflammatory arthritis, and conduct a comparison between the two models. Techniques such as PCR, immunofluorescence and electromyography (EMG) recording will be used in this project.

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Meesawatsom Pongsatorn (Den)

Dates: October 2013 - September 2017

Supervisor: V Chapman

Targeting the resolution of inflammation to reduce spinal excitability and pain

Resolvins are endogenous lipid mediators derived from docosahexaenoic acid (DHA, D-series) and eicosapentaenoic acid (EPA, E-series) that exhibit potent anti-inflammatory and pro-resolving properties. One of these products, known as aspirin triggered resolvin D1 (AT-RvD1), has robust analgesic lead compound for the treatment of pain from different origins, focusing on potential spinal mechanisms of action. I have demonstrated inhibitory effects of spinal AT-RvD1 in a model of acute inflammatory pain, but this effect is lost in a model of osteoarthritis pain. An ongoing study will evaluate its effects in a model of chemotherapy-induced peripheral neuropathic pain. Further studies will investigate the underlying mechanisms that lead to the differential inhibition of spinal nociceptive processing by AT-RvD1 in models of acute versus chronic pain.

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Nuria Casanova Vallve

Dates: January 2015 - September 2019

Supervisor: Victoria Chapman

Catherine Owles

Catherine Owles

Dates: May 2015 - September 2019

Supervisors: John Harris and Carl Stevenson

Investigations of the origins of altered pain perception in a commercial pig strain

This project examined the relationship between degenerative joint disease (osteoarthritis) and pain in commercial breeder pigs. Pain behaviours were evaluated in commercial pigs and the relationship to joint disorders evaluated by assessing joint chondropathy, changes in the phenotype of sensory nerves innervating the affected joint, changes in the spinal cord and changes in the synovium and synovial fluid. The results found in pigs were then compared to a well validated rodent model of osteoarthritis pain, with a secondary aim of the project to evaluate pig joint disease as a model of human osteoarthritis.

Monica Persson

Monica Persson

Dates: October 2015 - September 2019

Supervisors: Weiya Zhang

Relative efficacy of topical NSAIDs and topical capsaicin in osteoarthritis and neuropathic pain

The project aimed to better understand the mechanism of pain in osteoarthritis. It did so by identifying treatment responders, making comparisons between treatments with different mechanisms of action, and between osteoarthritic and neuropathic pain. Conventional, network, and individual patient data meta-analyses of randomised controlled trials evaluating the efficacy of topical NSAIDs and topical capsaicin in osteoarthritis were conducted. The relative efficacy of both treatments was assessed in osteoarthritis, and treatment responders was identified. Comparisons were made with randomised controlled trials of neuropathic pain.

Pain Centre Versus Arthritis

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