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

1. To systematically review published observational studies of long-term conditions in professional footballers compared to the general population.
2. 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.
3. 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.
4. To examine the association between knee OA and ankle/foot OA within footballers and general population controls using radiographic assessment.

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.  

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.

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.

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.